[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"National Cancer Institute (NCI)\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":689},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,327,0,25,[9,52,82,107,132,168,190,216,238,266,291,319,344,365,386,411,434,461,495,515,553,589,614,633,656],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":34,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":41,"startDateStruct":44,"completionDateStruct":46,"leadSponsor":48,"locationsCount":51},"100651303","phase-2-combination-bevacizumab-and-prgn-2012-in-adults-with-recurrent-respiratory-papillomatosis-rrp-100651303",false,"NCT07756840","Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)","A Phase II Study of Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)","* INCLUSION CRITERIA:\n* Histological or cytological diagnosis of RRP confirmed by pathology report. Note: If there is no documentation or archival sample, a biopsy will be done to confirm the diagnosis.\n* Age \\>= 18 years old.\n* A history of 2 or more surgeries or use of IV bevacizumab in order to control laryngeal and\u002For tracheal RRP within 12 months prior to the study treatment initiation.\n* Previous treatment with PRGN-2012 (zopapogene imadenovec \\[Papzimeos\\]).\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n* Participants must have an adequate organ and marrow function as defined below:\n\n  * White blood cells (WBC) \\>2,000\u002FmcL\n  * Absolute neutrophil count (ANC) \\>= 1,000\u002FmcL\n  * Hemoglobin \\> 9.0 g\u002FdL\n  * Platelets \\>= 100,000\u002FmcL\n  * Total bilirubin \\\u003C= 1.5 mg\u002FdL. Note: participants with Gilbert s Syndrome must have a total bilirubin \\\u003C 3.0 mg\u002FdL\n  * Aspartate aminotransferase (AST) \\\u003C= 2.5 X institutional upper limit of normal (ULN)\n  * Alanine aminotransferase (ALT) \\\u003C=2.5 X institutional ULN\n  * Creatinine within normal institutional limits OR Creatinine Clearance (CrCl) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 for participants with creatinine levels above institutional normal (calculated using the Cockcroft-Gault formula).\n  * Prothrombin time (PT) \u002F International normalized ratio (INR) and Partial thromboplastin time (PTT) \\\u003C= 1 X institutional ULN. In participants on anticoagulation, coagulation tests should be within a therapeutic range.\n  * Urinalysis Urine dipstick \\\u003C 2+ proteinuria. Participants with \\>= 2+ proteinuria on dipstick urinalysis should undergo a 24- hour urine collection and must demonstrate \\\u003C= 1g of protein in 24 hours to be eligible\n* Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization, abstinence) for the duration of treatment and up to 6 months after completion of the study treatment.\n\nMen must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of treatment and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period.\n\n* Women who are breastfeeding or plan to breastfeed must agree to discontinue breastfeeding from study treatment initiation.\n* Ability of participant to understand and sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* History of significant cardiovascular disease or thromboembolic event: cerebral vascular accident\u002Fstroke, myocardial infarction, unstable angina, congestive heart failure (\\>= New York Heart Association Classification Class II) occurring within 12 months prior to the study treatment initiation\n* Serious cardiac arrhythmia requiring medication as assessed by electrocardiogram (EKG) at screening.\n* Any investigational agents within 4 weeks prior to the study treatment initiation.\n* Systemic medical RRP therapy within 4 weeks or 3 half-lives, whichever is longer prior to the study treatment initiation.\n* Participants with a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the study treatment initiation. Note: Inhaled, topical intranasal or intraocular steroids, and adrenal replacement doses \\\u003C10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.\n* History of abdominal fistula or gastrointestinal perforation within 12 months prior to the study treatment initiation.\n* Major surgery within 4 weeks prior to the study treatment initiation. Note: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges).\n* Non-healing wounds, active ulcer, or untreated bone fracture.\n* History of hemoptysis (\\>2.5 mL of bright red blood per episode) within 1 month prior to the study treatment initiation.\n* History of serious hemorrhage (CTCAE Grade 4) within 12 months prior to the study treatment initiation.\n* Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation).\n* Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to the study treatment initiation.\n* Inadequately controlled hypertension (defined as systolic blood pressure (BP) \\>150 mmHg and\u002For diastolic blood pressure \\> 100 mmHg). Note: an average of 3 BP readings on 2 sessions will be used to measure blood pressure if the initial reading indicates inadequately controlled hypertension. Anti-hypertensive therapy to achieve blood pressures below these parameters is allowed.\n* Prior history of hypertensive crisis or hypertensive encephalopathy.\n* Persisting toxicity related to prior therapy of Grade \\>1 per CTCAE. Note: Alopecia, sensory neuropathy Grade \\\u003C= 2 are acceptable.\n* Known, active alcohol or drug abuse.\n* History of allergy to study drug components.\n* History of \\>= Grade 3 per CTCAE infusion-related reaction to bevacizumab or PRGN-2012.\n* Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in WOCBP at screening.\n* Uncontrolled symptomatic, intercurrent illness evaluated by medical history, physical exam, and labs, or social situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study, or that would limit compliance with study requirements.","ALL","18 Years","120 Years",{"count":21,"type":22},50,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","Background:\n\nRecurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths called papillomas to grow in the airway, most often in the voice box, windpipe, or lungs. These growths can make it hard to speak or breathe. Surgery can remove the papillomas, but they often come back. In some cases, they can become cancerous.\n\nObjective:\n\nThis study istesting whether two treatments used together (PRGN-2012, a vaccine-based treatment and bevacizumab, a drug that affects blood vessel growth) can help control RRP and reduce the chance that papillomas will grow back.\n\nEligibility:\n\nAdults aged 18 years and older may be able to join the study if they have RRP and meet certain treatment history requirements. This may include people who have previously received PRGN-2012 or bevacizumab, or people who have needed more than 2 surgeries to remove papillomas.\n\nDesign:\n\nBefore starting treatment, participants will have screening tests to make sure the study is safe for them. These tests may include a physical exam with blood and urine tests, heart function testing, imaging scans, and an endoscopy. During an endoscopy, a thin, flexible tube with a small camera will look at the inside of the nose, throat, voice box, and upper windpipe.\n\nParticipants will receive study treatment during 7 clinic visits over about 6 months. Bevacizumab is given through a vein amd PRGEN-2012 is given as an injection under the skin of the arm or leg. Participants may receive 1 or both drugs at each visit.\n\nAfter completing treatmen, participants will return for 4 follow-up visits over 1 year. These visits may include repeat imaging, blood and urine tests, and other exams. After that, the study team will contact participantsby phone or email every 3 months for 2 years.\n\nIf their RRP gets worse during the follow-up period, they may be able to receive a second course of treatment using the same schedule....",[28,29,30,31,32,33],"Respiratory Recurrent Papillomatosis (RRP)","Human Papillomavirus (HPV)","Papillomavirus Infection","Laryngeal Diseases","Tracheal Diseases","Respiratory Tract Neoplasm",[35,36,37,38],"HPV Vaccine","Gardasil","Papzimeos (zopapogene imadenovec-drba)","Bevacizumab (Avastin)","NOT_YET_RECRUITING","2026-08-20",{"date":42,"type":43},"2026-08-21","ACTUAL",{"date":45,"type":22},"2026-08-26",{"date":47,"type":22},"2030-07-01",{"name":49,"class":50},"National Cancer Institute (NCI)","NIH",1,{"id":53,"slug":54,"hasResults":12,"nctId":55,"briefTitle":56,"officialTitle":57,"acronym":4,"eligibilityCriteria":58,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":59,"targetDuration":4,"studyType":23,"phases":61,"briefSummary":63,"conditions":64,"keywords":70,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":77,"startDateStruct":78,"completionDateStruct":79,"leadSponsor":81,"locationsCount":51},"100648006","hepatic-artery-infusion-of-carfilzomib-in-participants-with-liver-metastatic-disease-previously-treated-with-hepatic-artery-infusion-pump-therapy-100648006","NCT07715903","Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy","Phase I Study Evaluating Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy","* INCLUSION CRITERIA:\n* Participants must have a histologically or cytologically confirmed by pathology report diagnosis of colorectal cancer (CRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC).\n* Participants must have measurable liver-dominant metastatic disease. Note: liver-dominant metastatic disease is defined as \\>=75% of metastatic disease present in the liver as assessed by the principal investigator.\n* Extrahepatic disease should be treated with anticancer therapy, if applicable, and should be stable by RECIST criteria for at least 6 weeks prior to study treatment initiation.\n* Participants must have previously undergone hepatic artery infusion pump therapy and have a functioning hepatic artery infusion pump in place.\n* Participants must have progressed on, been intolerant of, or have residual disease after HAI floxuridine and appropriate current standard-of-care treatment.\n* Age \\>= 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C= 2.\n* Participants must have an adequate organ and marrow function as defined below:\n\nLeukocytes \\> 3,000\u002FmcL\n\nHemoglobin \\>= 9 mg\u002FdL\n\nAbsolute neutrophil count \\> 1,500\u002FmcL\n\nPlatelets \\> 100,000\u002FmcL\n\nTotal bilirubin \\\u003C 2 X institutional upper limit of normal (ULN)\n\nAspartate aminotransferase (AST) \\\u003C 2.5 X institutional (ULN)\n\nAlanine aminotransferase (ALT) \\\u003C 2.5 X institutional (ULN)\n\nCreatinine \\\u003C2 X institutional (ULN)\n\n* Participants positive for human immunodeficiency virus (HIV) 1\u002F2 antibody must have a negative HIV viral load.\n* Participants positive for Hepatitis C (HCV) antibody must have a negative HCV viral load.\n* Participants positive for Hepatitis B (HBV) core antibody (HBcAb) must have a negative HBV viral load. Note: Participants positive for Hepatitis B surface antigen (HBsAg) are excluded.\n* Women of childbearing potential (WOCBP) must agree to use effective contraception (barrier, hormonal, intrauterine device, abstinence, surgical sterilization) at the study entry and up to 6 months after the last dose of the study drug. A participant may request a male partner to use an effective form of contraception to fulfill this requirement (e.g., condom\u002Fbarrier).\n\nMen must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 3 months after the last dose of the study drug. A participant may request a female partner to use an effective form of contraception to fulfill this requirement (e.g., intrauterine device, hormonal contraceptives). Men must not freeze or donate sperm within the same period.\n\n* Women who are breastfeeding or plan to breastfeed must agree to discontinue\u002Fpostpone breastfeeding from study treatment initiation through 2 weeks after the last dose of the study drug.\n* Ability of participant to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Participants with liver metastases amenable to resection.\n* Participants who received floxuridine within 6 weeks prior to the study treatment initiation.\n* Participants who received any anticancer therapy within 2 weeks prior to the study treatment initiation.\n* Participants who received any investigational agents within 4 weeks prior to the study treatment initiation.\n* Participants with incontrovertible radiographic evidence of disease progression per the RECIST definition outside of the liver within 3 months prior to the study treatment initiation. Note: Pulmonary lesions less than 1 cm are allowed.\n* Prior radiation to the liver (Yttrium-90 \\[Y-90\\] or External Beam Radiation Therapy \\[EBRT\\]).\n* History of allergic reactions attributed to compounds of similar chemical composition to CFZ.\n* Positive serum or urine Beta-human chorionic gonadotropin (Beta-HCG) pregnancy test performed at screening.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, evaluated by medical history, electrocardiogram (EKG), physical exam, and laboratory testing, or social situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.",{"count":60,"type":22},20,[62],"PHASE1","Background:\n\nCancers that begin in the colon, adrenal glands, or bile ducts may spread to the liver. These liver tumors are often treated using a hepatic artery infusion (HAI) pump. The HAI pump is installed in the artery that goes to the liver; drugs are administered directly to the liver through this pump. But these tumors often return after treatment. Carfilzomib (CFZ) is a drug approved to treat another kind of cancer. Researchers want to find out if this drug may be helpful when administered through the HAI pump directly to the liver for people with colon, adrenal glands, or bile duct cancer that has spread to the liver.\n\nObjective:\n\nTo test the safety of carfilzomib (CFZ) delivered via a hepatic artery infusion (HAI) pump directly to the liver in people with cancer in their liver.\n\nEligibility:\n\nPeople aged 18 years or older with cancers of the colon, adrenal glands, or bile ducts that spread to the liver and persist after treatment. They must have a functioning hepatic artery infusion (HAI) pump in place from previous treatment of HAI pump therapy.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam, blood tests, imaging scans, and a test of their heart function. They will also have a test to show how the blood flows through their liver: A radioactive substance will be injected into a vein, and a special camera will take pictures of the blood flow for up to 1 hour.\n\nParticipants will receive the study drug for about 6 months. They will visit the clinic once a week. Their HAI pump will be filled with the drug at each visit; the drug will slowly drain from the pump into the liver. Blood tests and imaging scans will be repeated during the study.\n\nParticipants will have follow-up visits 1 and 3 months after their last dose of study drug.\n\nAn optional liver biopsy (tissue sample) for research purposes may be done before the study drug is given, and again (optional) within 28 days after first receiving the study drug. Individuals may participate in the study even if they do not agree to have the biopsies done.\n\n...",[65,66,67,68,69],"Colorectal Neoplasms","Neoplasms","Intrahepatic Cholangiocarcinoma","Adrenocortical Carcinoma","Metastasis, Neoplasm",[71,72,73,74,75,76],"Hepatic artery infusion","Carfilzomib","Colorectal Cancer","Intrahepatic cholangiocarcinoma","Adrenocortical Cancer","Measurable liver metastasis",{"date":42,"type":43},{"date":45,"type":22},{"date":80,"type":22},"2031-12-31",{"name":49,"class":50},{"id":83,"slug":84,"hasResults":12,"nctId":85,"briefTitle":86,"officialTitle":87,"acronym":4,"eligibilityCriteria":88,"healthyVolunteers":12,"sex":89,"minAge":18,"maxAge":19,"enrollmentInfo":90,"targetDuration":4,"studyType":23,"phases":92,"briefSummary":93,"conditions":94,"keywords":97,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":102,"startDateStruct":103,"completionDateStruct":104,"leadSponsor":106,"locationsCount":51},"100645567","il-15-superagonist-with-or-without-vaccine-in-biochemically-recurrent-prostate-cancer-after-previous-stereotactic-body-radiation-therapy-100645567","NCT07686380","IL-15 Superagonist With or Without Vaccine in Biochemically Recurrent Prostate Cancer After Previous Stereotactic Body Radiation Therapy","Phase II Trial of IL-15 Superagonist With or Without Vaccine in Biochemically Recurrent Prostate Cancer After Previous Stereotactic Body Radiation Therapy","* INCLUSION CRITERIA:\n* Histopathological confirmation of prostate adenocarcinoma by the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center prior to the study treatment initiation. If no pathologic specimen is available, participants may enroll with a pathologist s report showing a histologic diagnosis of prostate adenocarcinoma and a clinical course consistent with the disease from any outside site.\n* Biochemically recurrent prostate cancer, defined as PSA over 0.8 ng\u002Fml following radical prostatectomy or \\>= 2 ng\u002Fml above the nadir following definitive radiotherapy or definitive radiotherapy (including brachytherapy) for localized prostate cancer.\n* Participants must be at least 1 year removed from definitive local therapy before the study treatment initiation.\n* Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation.\n* Hepatic function eligibility parameters: Bilirubin (total and direct) \\\u003C= upper limit of normal (ULN) (OR in participants with Gilbert s syndrome, a total bilirubin \\\u003C= 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) \\\u003C= 1.5 times upper limit of normal.\n* Adequate renal function defined by a calculated creatinine clearance \\> 50 mL\u002Fmin according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.\n* ECOG performance score 0-1.\n* No other active malignancies within the 36 months prior to the study treatment initiation (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder).\n* 18 years of age or older.\n* Individuals must agree to use effective contraception (barrier, vasectomy and\u002For abstinence) for the duration of study therapy and for four months after the last treatment administration. Individuals with partners with birthing potential will be recommended that their partner use a highly effective contraception (includes use of oral, injected or implanted hormonal methods of contraception, placement of certain intrauterine devices (IUD) or intrauterine systems (IUS), hysterectomy, oophorectomy, salpingectomy.\n* Individuals must agree to not donate sperm during the restricted period (for the duration of study therapy and for four months after the last dose of study treatment).\n* Negative CT scan\u002F Magnetic resonance imaging (MRI) for evidence of soft tissue metastasis (visceral or lymph node).\n* Negative Tc99 for evidence of bone disease.\n* Participants must have had prior SBRT to PSMA+ findings beyond the prostate and have had a documented 25% or more PSA rise from post-SBRT nadir\n* Baseline testosterone \\>= 100 ng\u002Fdl.\n* Hematological parameters:\n\n  * Granulocyte count \\>= 1000\u002Fmm\\^3\n  * Platelet count \\>= 100000\u002Fmm\\^3\n  * Hemoglobin (Hgb) \\>= 10 g\u002FdL\n* Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Immunocompromised status due to:\n\n  * Human immunodeficiency virus (HIV) seropositivity\n  * HBV or HCV seropositivity\n  * Other immunodeficiency diseases\n* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed. Participants with diabetes type I, vitiligo, or alopecia are allowed.\n* Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).\n* Chronic administration (defined as daily or every other day for continued use \\> 14 days) of systemic corticosteroids within 28 days before the study treatment initiation. Note: Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.\n* Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 28 days prior to the study treatment initiation.\n* Major surgery within 28 days prior to study treatment initiation.\n* Systemic therapy, including any investigational therapy within 28 days prior to the study treatment initiation.\n* Radiation therapy within 14 days prior to the study treatment initiation.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.\n* Clinically significant cardiovascular\u002Fcerebrovascular disease as follows: cerebral vascular accident\u002Fstroke (\\\u003C 6 months prior to the first planned dose of study drugs), myocardial infarction (\\\u003C 6 months prior to the first planned dose of study drugs), or any of the following at time of enrollment: unstable angina, congestive heart failure (New York Heart Association Classification Class \\>= II), serious cardiac arrhythmia, or uncontrolled hypertension (SBP\\>170\u002F DBP\\>105).\n* Serious intercurrent medical illness evaluated by medical history and physical exam that would interfere with participant's ability to carry out the treatment program.","MALE",{"count":91,"type":22},65,[25],"Background:\n\nBiochemically recurrent prostate cancer (BCR) occurs when prostate-specific antigen (PSA) levels in the blood rise after surgery or radiation. BCR affects 30,000 to 50,000 men each year. Researchers want to know if a drug (N-803) alone or combined with a vaccine (ETBX-071) can reduce PSA in BCR prostate cancer after radiation.\n\nObjective:\n\nTo test a study drug alone and combined with a vaccine in people with BCR prostate cancer who have been treated with targeted radiation to areas of recurrent prostate cancer in the past.\n\nEligibility:\n\nPeople aged 18 years and older with BCR prostate cancer who have previously undergone treatment with stereotactic body radiation therapy (SBRT).\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and kidney function. They will have 3 different imaging scans of their tumors.\n\nN-803 is injected under the skin of the abdomen. ETBX-071 is injected under the skin of thigh.\n\nParticipants will be divided into 2 groups: 1 group will get N-803 alone; 1 group will get both N-803 and ETBX-071.\n\nThe drug or drugs will be given on the first day of 21-day treatment cycles. Participants will have 8 treatment cycles.\n\nParticipants will have a follow-up visit 3 weeks after their last dose of the study drugs. Blood tests and all 3 imaging scans will be repeated.\n\nFollow-up visits will continue every 4 to 8 weeks for 5 years. These visits will include a positron emission tomography (PET) scan every 6 months.",[95,96],"Recurrent Prostate Cancer","Prostate Cancer",[95,98,99,100,101],"IL-15 Superagonist","N-803","ETBX-071","PSA Vaccine",{"date":42,"type":43},{"date":45,"type":22},{"date":105,"type":22},"2029-01-30",{"name":49,"class":50},{"id":108,"slug":109,"hasResults":12,"nctId":110,"briefTitle":111,"officialTitle":112,"acronym":4,"eligibilityCriteria":113,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":114,"targetDuration":4,"studyType":23,"phases":116,"briefSummary":117,"conditions":118,"keywords":121,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":127,"startDateStruct":128,"completionDateStruct":129,"leadSponsor":131,"locationsCount":51},"100644770","il-12-genetically-engineered-myeloid-cells-in-participants-with-relapsed-refractory-solid-tumors-100644770","NCT07672483","IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors","Phase I Trial of IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors","* INCLUSION CRITERIA:\n* Relapsed or refractory solid tumor malignancies for whom standard measures do not exist or are no longer effective. Must have histologic confirmation of original diagnosis or relapse.\n* Participants must have evaluable (measurable or not measurable) disease.\n* Part B only: Participants must:\n\n  * be willing to undergo mandatory pre- and post-treatment tumor biopsies. Tumor tissue should either be taken from non-target lesions or from target lesions where sampling can be done without impacting lesion measurement\n\nand\n\n--have disease amenable to biopsy to allow to perform pre- and post-tumor biopsies.\n\n* Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy and close monitoring for over 3 months shows no active progression.\n* At least one prior cancer treatment when upfront standard therapy exists. Note: There is no limit to the number or type of prior treatment regimens.\n* The indicated time must have elapsed since any systemic anti-cancer therapy prior to leukapheresis.\n* Age \\>= 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C= 2.\n\nNote: Participants who are unable to walk because of paralysis, but who are able to maintain supine position independently in a wheelchair, will be considered ambulatory for the purpose of performance status.\n\n* Participants must have adequate organ and marrow function as defined below:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Hemoglobin (Hgb) \\>= 8 g\u002FdL (transfusion independent)\n  * Prothrombin time (PT) \\\u003C= 1.5 X institutional upper limit of normal (ULN) (Part B only, participants undergoing biopsy)\n  * Creatinine clearance \\>= 60 mL\u002Fminute\u002F1.73m\\^2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)\n  * Aspartate Aminotransferase (AST) \\\u003C= 3 X institutional ULN\n  * Alanine Aminotransferase (ALT) \\\u003C= 3 X institutional ULN\n  * Total bilirubin \\\u003C= 1.5 institutional ULN. Note: In the case of Gilbert's syndrome total bilirubin \\\u003C= 3 X ULN\n  * Serum albumin \\>= 2.7 g\u002FdL\n  * Ejection fraction of \\>= 45% and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram (ECHO).\n  * QTc interval \\\u003C 480 msec\n  * Oxygen saturation \\>92% on room air at rest\n* Participants with a clinical history of prolonged smoking (\\>= 10 pack-years), lung disease, or current or recent history of respiratory symptoms must have a forced expiratory volume in the first second (FEV1) \\> 50%.\n* Participants seropositive for human immunodeficiency virus (HIV) must have an undetectable HIV viral load.\n* Participants seropositive for Hepatitis C virus (HCV) must have an undetectable HCV viral load\n* Participants positive for Hepatitis B surface antigen (HbsAg) must have an undetectable Hepatitis B virus (HBV) viral load.\n* Women of childbearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \\[IUD\\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy.\n\nNote: WOCBP is defined as any woman who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.\n\nMen able to father a child must agree to use a highly effective method of contraception (surgical sterilization, abstinence or man may request that partner uses the highly effective form of contraception to fulfill this requirement) at the study entry and up to 7 months after the last dose of study drugs. Men able to father a child must not freeze or donate sperm within the same period.\n\n* Nursing participants must be willing to discontinue nursing from study treatment initiation through 12 months after the last dose of the study drug(s).\n* Ability and willingness of participant to enroll on protocol 15-C-0028, Follow-Up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials after 5 years.\n* Ability of the participant to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Participants with history of primary CNS tumors or leptomeningeal disease.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, IL-12, or other agents used in the study.\n* Concurrent untreated opportunistic infections as evidenced by history, blood test or imaging at screening.\n* Active systemic infections requiring anti-infective treatment.\n* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) or secondary\u002Facquired immunodeficiency requiring steroids or other non-steroid immunosuppressive agents.\n* History of clonal hematopoiesis of indeterminate potential (CHIP) or myelodysplasia\u002Fmyelodysplastic syndrome (MDS) or monoclonal gammopathy of undetermined significance (MGUS).\n* Participants with symptomatic pleural effusions requiring intervention or with recent history (within 3 months) of pleural effusions that required intervention.\n* Participants with ischemic symptoms (may include chest pain\u002Fpressure, shortness of breath, nausea, vomiting, sweating, and\u002For pain in the neck, shoulder, jaw or arm) confirmed by stress test OR a history of coronary revascularization (unless the participant has a normal cardiac stress test after revascularization and within 12 months prior to leukapheresis).\n* Any form of diagnosed autoimmune disease requiring immune suppression as well as participants with active autoimmune skin diseases such as psoriasis or any history of active systemic autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression\u002Fsystemic disease-modifying agents within the last 2 years. Exceptions will be allowed for vitiligo and hypothyroidism that has been stable on thyroid replacement medications for \\> 6 weeks prior to leukapheresis.\n* Any participant who developed autoimmunity (\\>= grade 3 per CTCAE v. 6.0) with checkpoint inhibitor use. Note: Exceptions will be allowed for vitiligo and hypothyroidism that has been stable on thyroid replacement medications for \\> 6 weeks prior to leukapheresis.\n* Participants who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to leukapheresis or anticipated to need a major surgical procedure during the study.\n* History of prior solid organ transplantation.\n* Participants that require urgent therapy due to tumor mass effects or spinal cord compression within 2 weeks prior to leukapheresis.\n* Any investigational therapy within 2 weeks prior to leukapheresis.\n* Pregnancy confirmed with Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in WOCBP at screening. Note: In case of a suspected false-positive serum or urine test result, additional evaluation must be done to rule out pregnancy.\n* Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history, physical exam, or situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.",{"count":115,"type":22},95,[62],"Background:\n\nMyeloid cells are a type of immune cell found in most tumors. Interleukin 12 (IL-12) is a protein that helps the immune system kill tumor cells. Researchers want to know if myeloid cells that have been genetically engineered to produce IL-12 (IL-12 GEMys) can activate the immune system to attack cancer cells in solid tumors.\n\nObjective:\n\nTo test IL-12 GEMys in people with cancer.\n\nEligibility\n\nPeople aged 18 years and older with cancer that returned or failed to respond to treatment.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans of their tumors. A sample of tumor tissue may be taken.\n\nParticipants will have daily injections for few days to prepare them to undergo leukapheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will be modified in a lab to create IL-12 GEMys.\n\nParticipants will check in to the hospital. They will receive drugs for 5 days to prepare their body for the treatment. Then they will have their own IL-12 GEMys infused through a needle inserted into a vein. They will stay in the hospital until they are well enough to go home. This may be 7 to 14 days or longer.\n\nSome participants may receive a second treatment with IL-12 GEMys within 2 years after the first.\n\nParticipants will have follow-up visits for about 5 years. These will include imaging scans and blood tests.",[119,120],"Relapsed Solid Tumor Malignancies","Refractory Solid Tumor Malignancies",[122,123,124,125,126],"GEMys","Cd34+ Cells","Lymphodepletion","IFNy","Leukapheresis",{"date":42,"type":43},{"date":45,"type":22},{"date":130,"type":22},"2029-01-15",{"name":49,"class":50},{"id":133,"slug":134,"hasResults":12,"nctId":135,"briefTitle":136,"officialTitle":137,"acronym":4,"eligibilityCriteria":138,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":139,"targetDuration":4,"studyType":23,"phases":141,"briefSummary":142,"conditions":143,"keywords":155,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":163,"startDateStruct":164,"completionDateStruct":165,"leadSponsor":167,"locationsCount":51},"100643883","docetaxel-and-sx-682-in-recurrentmetastatic-head-and-neck-squamous-cell-carcinoma-salivary-gland-carcinoma-and-advanced-prostate-cancer-100643883","NCT07667400","Docetaxel and SX-682 in Recurrent\u002FMetastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer","Phase I\u002FII Trial of Docetaxel and SX-682 in Recurrent\u002FMetastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer","* INCLUSION CRITERIA:\n\nAll Participants\n\n* Age \\>= 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) \\\u003C= 2\n* Participants must have adequate organ and marrow function as defined below:\n\n  * ANC \\>= 1,500\u002FmcL\n  * Hemoglobin (Hgb) \\>= 9 g\u002FdL\n  * Platelets (PLTs) \\>= 100,000\u002FmcL\n  * Creatinine clearance \\>= 50 mL\u002Fmin (by Cockroft-Gault formula)\n  * Total bilirubin \\\u003C= 1.5 x iULN (\\\u003C= 3 x ULN in participants with known\u002Fsuspected Gilbert s disease)\n  * ALT\u002FAST \\\u003C= 2.5 x iULN\n  * Activated partial thromboplastin time (aPTT) \\\u003C= 1.5 x iULN\n* Contraception as follows:\n* Women of child-bearing potential (WOCBP) must agree to use an effective method of contraception (barrier, hormonal, intrauterine device \\[IUD\\], surgical sterilization, abstinence) prior to study entry, for the duration of study treatment, and for up to 2 months after discontinuation of the study drugs. A participant may request a male partner to use an effective form of contraception to fulfill this requirement.\n* Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 4 months after discontinuation of the study drugs. A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men able to father a child must not freeze or donate sperm within the same period.\n* Nursing participants must be willing to discontinue nursing from study treatment initiation through one week after the last dose of study drugs.\n* Participants must be able to swallow oral medications.\n* Human immunodeficiency virus (HIV)-infected participants must have undetectable viral load (VL) and be on effective anti-retroviral therapy within 4 weeks prior to the study treatment initiation and have no history of opportunistic infections or Castleman s disease within 12 months prior to the study treatment initiation.\n* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV VL.\n* Participants with evidence of chronic hepatitis C virus (HCV) infection must have undetectable HCV VL.\n* Participants must be able to understand and willing to sign a written informed consent document.\n\nParticipants with HNC\n\n* Histologically confirmed HNSCC (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses, nasopharynx) or SGC (including ACC and non-ACC) and recurrent\u002Fmetastatic (R\u002FM) or advanced incurable disease.\n* Prior treatment as follows:\n\n  * Participants with R\u002FM HNSCC must have prior systemic treatment (platinum-based chemotherapy and\u002For anti-PD(L)1 treatment).\n  * Participants with R\u002FM SGC may have any number of prior systemic treatment lines; prior systemic treatment not required for participation.\n  * Participants must not have received systemic anticancer treatment within 3 weeks prior to first treatment administration. Note: Treatment-related toxicities must have resolved to Grade \\\u003C2 or be minimal and not constitute a safety risk. Participants with SGC previously treated with hormonal therapies (e.g., drugs targeting the androgen receptor) may continue these drugs concomitantly with study therapy. Participants with bone metastases or hypercalcemia on intravenous bisphosphonate medications, denosumab, or similar agents, are eligible to participate and may continue this treatment.\n* Presence of \\>= 1 measurable lesion by RECIST v 1.1 criteria.\n\nParticipants with mCRPC\n\n* Documented histopathological confirmation of prostate cancer. If no pathologic report or specimen is available, participants may enroll with a history of clinical course consistent with the disease.\n* Participants must have mCRPC, defined as at least one lesion on TC-99 bone scan or at least one lesion that is measurable per RECIST 1.1.\n* Participants must need ADT as part of their cancer therapy (unless previous orchiectomy)\n* Castrate testosterone level (\\\u003C50 ng\u002Fdl or 1.7 nmol\u002FL)\n* Prior treatment as follows:\n\n  * DTX for mCRPC is allowed but participants must not have had progression while on docetaxel or within 3 months after completing DTX for mCRPC\n  * Participants must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.\n* Progression defined as two consecutive rising PSA values at least 1 week apart or radiographic evidence of progression seen on computed tomography (CT) scan or TC- 99 bone scan.\n* Toxicities related to prior therapy, including surgery and\u002For radiation, must have resolved to \\\u003C Grade 1 per CTCAE v.6.0.\n\nEXCLUSION CRITERIA:\n\nAll participants\n\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to DTX, SX-682, or other agents used in study (e.g., polysorbate 80).\n* Known active brain metastases. Note: Participants with previously treated brain metastases are eligible if imaging at least four weeks prior to first trial treatment shows no evidence of progression and neurologic symptoms have resolved, have no new or enlarging brain metastases, and are not using glucocorticoids for at least a week prior to first trial treatment\n* Participants must not have received other investigational agents within 3 weeks prior to the first dose of the study drug(s).\n* Participants must not have received major surgery within 14 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). If participant underwent major surgery, they must have recovered adequately (according to the Principal Investigator) from the toxicity and\u002For complications from the intervention prior to starting study treatment.\n* Treatment (systemic) with any medications or substances that are moderate or strong inducers or moderate or strong inhibitors of cytochrome P450 (CYP3A4) listed at https:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdrug-interactions-labeling\u002Fdrug-development-and-druginteractions- table-substrates-inhibitors-and-inducers#table2-2,table3-3,table5-2 within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of the study treatment.\n* Prior or concurrent malignancy whose natural history or treatment has potential to interfere with the safety or efficacy assessment of the study treatment.\n* Participants with serious uncontrolled intercurrent illness evaluated by medical history, electrocardiogram (EKG), and physical exam that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.\n\nParticipants with HNC\n\n* Participants must not have received large-field radiotherapy within 2 weeks prior to first treatment administration. All residual treatment-related toxicities must have resolved to Grade \\\u003C2 (except for radiation-induced xerostomia\u002Fdysgeusia) or be minimal and not constitute a safety risk.\n* Positive pregnancy serum or urine beta-human chorionic gonadotropin (beta-hCG) test\n\nParticipants with mCRPC\n\n* Use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 1 week prior to the study treatment initiation.\n* Cancer related neuropathy at screening\n* Baseline QTcF \\>= 470 ms",{"count":140,"type":22},120,[62,25],"Background:\n\nHead and neck cancers (HNCs) account for about 5% of all cancers worldwide. They grow in the mouth, throat, nasal cavity, or salivary glands. Prostate cancer is the most common cancer in men in the United States. Survival rates for these cancers are lower than 50% if they spread to other parts of the body or return after treatment. Better treatments are needed.\n\nObjective:\n\nTo test a new drug (SX-682), combined with an approved drug (docetaxel, or DTX), in people with HNCs or prostate cancer.\n\nEligibility\n\nPeople aged 18 years and older with an HNC or prostate cancer that has returned after treatment or has spread.\n\nDesign:\n\nParticipants will be screened. They will have blood tests, imaging scans, and a test of their heart function. A tissue sample (biopsy) of the tumor may be taken.\n\nParticipants will take the study drugs in 3-week cycles. SX-682 is a tablet taken by mouth twice a day from Days 1 to 11 of each cycle. Participants will get a supply of the drug to take home. DTX is given on Day 8 of each cycle through a tube attached to a needle inserted into a vein in the arm. Participants will come to the clinic on Days 1 and 8 of every cycle. They will take both drugs for up to 6 cycles.\n\nParticipants will have follow-up visits 1 week and 1 month after they finish taking the drugs. Follow-ups will continue every 3 months for 2 years. Then they will have phone or email check-ins twice a year until 5 years have passed.",[144,145,146,147,148,149,150,151,152,153,96,154],"Head and Neck Cancer","Head and Neck Squamous Cell Carcinoma","Paranasal Sinus Neoplasms","Nasopharyngeal Carcinoma","Oropharyngeal Squamous Cell Carcinoma","Hypopharyngeal Cancer","Carcinoma of Larynx","Oral Squamous Cell Carcinoma","Salivary Gland Cancer","Adenoid Cystic Carcinoma","Metastatic Castration Resistant Prostate Cancer",[156,157,158,159,160,161,162],"Solid Tumors","Infusion","Chemotherapy","Carcinoma","Head and Neck","Prostate","molecule inhibitor",{"date":42,"type":43},{"date":45,"type":22},{"date":166,"type":22},"2037-10-01",{"name":49,"class":50},{"id":169,"slug":170,"hasResults":12,"nctId":171,"briefTitle":172,"officialTitle":173,"acronym":4,"eligibilityCriteria":174,"healthyVolunteers":12,"sex":89,"minAge":18,"maxAge":19,"enrollmentInfo":175,"targetDuration":4,"studyType":23,"phases":177,"briefSummary":178,"conditions":179,"keywords":183,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":185,"startDateStruct":186,"completionDateStruct":187,"leadSponsor":189,"locationsCount":51},"100641793","multitargeted-recombinant-ad5-psamuc-1brachyury-based-immunotherapy-triadeno-vaccine-with-il-15-superagonist-n-803-in-participants-with-clinically-localized-prostate-cancer-undergoing-active-surveillance-100641793","NCT07574541","Multitargeted Recombinant Ad5 PSA\u002FMUC-1\u002FBrachyury-Based Immunotherapy (TriAdeno) Vaccine With IL-15 Superagonist N-803 in Participants With Clinically Localized Prostate Cancer Undergoing Active Surveillance","Phase II Trial of a Multitargeted Recombinant Ad5 PSA\u002FMUC-1\u002FBrachyury-based Immunotherapy (TriAdeno) Vaccine With IL-15 Superagonist N-803 in Participants With Clinically Localized Prostate Cancer Undergoing Active Surveillance","* INCLUSION CRITERIA:\n* Histologically confirmed diagnosis of organ confined, low- or intermediate-risk PCa (Gleason grade group 1 or 2) identified in at least one prostate biopsy core. Biopsies performed at outside institutions should have Gleason score confirmed at the NCI by a genitourinary (GU) pathologist.\n* Participants must be on active surveillance.\n* Pre-study treatment tissue availability (at least one formalin-fixed paraffin embedded \\[FFPE\\] biopsy core or one H and E-stained slide and at least 5 unstained slides) obtained between 3 and 24 months prior to treatment initiation is mandatory for study initiation.\n* Serum PSA level of \\\u003C20 ng\u002FmL (or \\\u003C10ng\u002FmL for participants being treated with 5- alpha-reductase inhibitors)\n* Clinical stage \\\u003C=T2a by digital rectal exam (DRE)\n* Age \\>=18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C=1.\n* Adequate organ and marrow function as defined below:\n\n  * Absolute neutrophil count (ANC) \\>=1.0 x 109\u002FL\n  * Hemoglobin (Hgb) \\>=9 g\u002FdL\n  * Platelets \\>=75,000\u002FmcL\n  * Prothrombin International Normalized Ratio (INR) \\\u003C1.5 x upper limit of normal (ULN)\n  * Partial thromboplastin time (PTT) \\\u003C1.5 x ULN\n  * Total bilirubin \\\u003C1.5 x ULN\n  * Aspartate aminotransferase (AST) \\\u003C=2.5 x ULN\n  * Alanine aminotransferase (ALT) \\\u003C=2.5 x ULN\n  * Creatinine \\\u003C=1.5 x ULN\n\nOR\n\n--Calculated Creatinine clearance \\>=40 mL\u002Fmin\u002F1.73 m2 for individuals with creatinine levels above institutional normal (using either Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\] equation)\n\n* Treatment with steroid therapy must have a washout of at least 6 weeks prior to initiation of study treatment. Physiologic (replacement) doses of steroids as well as nasal, topical, or inhaled steroids are allowed.\n* Vaccination with a live (attenuated) vaccine (e.g., FluMist(R)) or a killed (inactivated)\u002Fsubunit vaccine (e.g., PNEUMOVAX(R), Fluzone(R)) must occur not sooner than 28 days or 14 days, respectively, prior to initiation of study treatment.\n* Participants must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to one (1) month after the last vaccine injection. We also will recommend participants with female partners of childbearing potential to ask them to be on highly effective birth control (hormonal, intrauterine device \\[IUD\\], surgical sterilization). Participants must not freeze or donate sperm within the same period.\n* Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Prior treatment for PCa by surgery, radiation, local ablative (i.e., cryosurgery or highintensity focused ultrasound), or androgen-deprivation therapy.\n* Evidence of PCa with metastatic disease.\n* Prior treatment with adenovirus-based vector immunotherapy, adenovirus-based vaccines, or investigational vaccines.\n* Prior solid organ or bone marrow transplant.\n* Immunodeficiency or splenectomy.\n* Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV), confirmed by PCR, and hepatitis B virus (HBV) and hepatitis C virus (HCV), as determined by hepatitis B surface antigen (HBsAg) and HCV serology.\n* History of autoimmune disease (active or past), except for autoimmune-related thyroid disease, type I diabetes, and vitiligo if the condition(s) is well controlled.\n* History of heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly\n\ncontrolled angina, or history (\\\u003C1 year prior to initiation of study therapy) of ventricular arrhythmia.\n\n* Acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions.\n* Second malignancy within 3 years prior to initiation of study therapy. Note: Individuals with curatively treated non-melanoma skin cancers or non-muscle invasive bladder cancer will not be excluded.\n* History of herbal products that may decrease PSA levels (e.g., saw palmetto).\n* Participants who have undergone surgery within 4 weeks prior to initiation of study therapy.\n* Participants receiving any other investigational agents within 30 days prior to initiation of study therapy.\n* History of allergic reaction attributed to compounds of similar chemical or biological composition to the study drugs.\n* Uncontrolled intercurrent illness that would limit compliance with study requirements suggested by medical history, physical examination, or standard clinical assessments such as imaging, EKG, and laboratory studies.",{"count":176,"type":22},52,[25],"Background:\n\nProstate cancer is the second most common cause of cancer-related death among men in the United States. Early-stage, low-grade prostate cancer is managed with active monitoring. However, 35% of men with this cancer will need treatment within 5 years because of tumor growth. Researchers want to know if a new vaccine that targets 3 anti-cancer proteins (TriAdeno) plus a drug (N-803) approved for bladder cancer can help stop prostate tumors from growing.\n\nObjective:\n\nTo test TriAdeno and N-803 in people with early-stage prostate cancer.\n\nEligibility:\n\nPeople aged 18 years and older with early-stage low- or medium-risk prostate cancer.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have an imaging scan. They may have a rectal exam.\n\nTriAdeno is injected under the skin of the upper thigh; N-803 is injected under the skin of the abdomen. Participants will be treated in up to four 21-day cycles. They will get both injections on the first day of each cycle.\n\nParticipants may opt to complete a memory aid: They may record all of their symptoms for 7 days after each injection. They may also complete a questionnaire about their prostate symptoms.\n\nBlood tests, imaging scans, and other tests will be repeated during the study.\n\nA tissue sample (biopsy) of the tumor will be collected during or after cycle 2; a second biopsy may be taken about 1 year later.\n\nParticipants will have follow-up phone calls for 5 years....",[180,96,66,159,181,182],"Adenocarcinoma","Neoplasms, Glandular and Epithelial","Neoplasms by Histologic Type",[184],"Immune Infiltration",{"date":42,"type":43},{"date":45,"type":22},{"date":188,"type":22},"2028-06-15",{"name":49,"class":50},{"id":191,"slug":192,"hasResults":12,"nctId":193,"briefTitle":194,"officialTitle":195,"acronym":4,"eligibilityCriteria":196,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":197,"targetDuration":4,"studyType":199,"phases":4,"briefSummary":200,"conditions":201,"keywords":206,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":211,"startDateStruct":212,"completionDateStruct":213,"leadSponsor":215,"locationsCount":51},"100638410","collection-of-csf-samples-from-participants-with-metastatic-triple-negative-breast-cancer-tnbc-and-her2-breast-cancer-with-no-prior-history-nor-active-radiographically-detectable-brain-metastases-100638410","NCT07619534","Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases","Sample Collection Study to Analyze Cerebral Spinal Fluid as a Biomarker for Brain Metastasis in Metastatic Breast Cancer","* INCLUSION CRITERIA:\n* Pathology documentation of histologically confirmed HER2+ BC or TNBC with a history of metastatic disease.\n* Participants must be able to undergo lumbar puncture (LP) and brain MRI.\n* Women age \\>= 18 years\n* Adequate organ function as defined below:\n\n  * Creatinine \\\u003C=1.5 x institutional upper limit of normal (ULN)\n\nOR\n\n--Calculated Creatinine clearance \\>=40 mL\u002Fmin\u002F1.73 m2 for individuals with creatinine levels above institutional ULN (using either Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\] equation)\n\n\\- Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Prior history or current MRI-detected brain metastasis or leptomeningeal disease\n* Previous history of any invasive malignancies, except for surgically resected local cutaneous malignancies.\n* Pregnancy",{"count":198,"type":22},139,"OBSERVATIONAL","Background:\n\nBreast cancer is the most common cancer among women. It can often spread to the liver, lungs, bones, or brain. Breast cancer that spreads to the brain is often fatal. Researchers want to know if tumor DNA found in spinal fluid, blood, or tumor tissue can help predict when the cancer will spread to the brain. They want to collect these fluid and tissue samples for research.\n\nObjective:\n\nTo collect spinal fluid and other samples from people with breast cancer that has spread to other parts of the body.\n\nEligibility:\n\nPeople aged 18 years and older with HER2-positive or triple negative breast cancer. The cancer must have spread to other parts of the body but not to the brain.\n\nDesign:\n\nParticipants will be screened. They will have blood tests to assess kidney function. They will have an imaging scan of the brain.\n\nParticipants will come to the NIH clinic to have their samples collected:\n\n* Spinal fluid. A thin needle will be inserted into the lower back to draw out a sample of fluid from the space around the spinal cord. A physical exam and blood tests will be done to make sure it is safe for participants to have this procedure.\n* Blood.\n* Saliva or cheek swabs. They will rub a cotton swab inside of their mouth.\n* Tumor samples. If participants have had samples of tumor tissue (biopsies) collected in the past, leftover tissue may be used for this study.\n\nParticipants will be contacted for follow-up every 6 months for 3 years. They may return once a year to provide further samples.",[202,203,204,205],"Breast Cancer","Breast Carcinoma","Cancer of the Breast","Malignant Neoplasm of Breast",[207,208,209,210],"Triple Negative Breast Cancer (TNBC)","HER2-Postitive","Metastatic Breast Cancer","Cerebral Spinal Fluid Collection",{"date":42,"type":43},{"date":45,"type":22},{"date":214,"type":22},"2034-07-01",{"name":49,"class":50},{"id":217,"slug":218,"hasResults":12,"nctId":219,"briefTitle":220,"officialTitle":221,"acronym":4,"eligibilityCriteria":222,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":223,"targetDuration":4,"studyType":23,"phases":225,"briefSummary":226,"conditions":227,"keywords":230,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":233,"startDateStruct":234,"completionDateStruct":235,"leadSponsor":237,"locationsCount":51},"100636934","anti-crlf2-rtslpr-chimeric-antigen-receptor-t-cells-tslpr-cart-in-participants-with-recurrent-or-refractory-crlf2-rtslpr-overexpressing-b-cell-acute-lymphoblastic-leukemia-b-all-100636934","NCT07572136","Anti-CRLF2-R\u002FTSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R\u002FTSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)","Phase I Dose Escalation Study of Anti-CRLF2-R\u002FTSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R\u002FTSLPR-Overexpressing B-cell Acute Lymphoblastic Leukemia (B-ALL)","* INCLUSION CRITERIA:\n\n  1. Documentation of pathologic confirmation of a diagnosis of B-Cell acute lymphoblastic leukemia (ALL).\n  2. TSLPR+ expression must be detected on \\>=80% of the malignant cells by NSR device. Note: TSLPR+ expression does not need to be repeated by NSR device if there is a documentation of TSLPR surface expression by flow cytometry from a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory.\n  3. Participants must have a disease that is relapsed or refractory after initial systemic therapy and at least one salvage treatment, and must either be ineligible for, cannot access in a timely manner, or declined alternative curative options (including commercial CAR Tcell constructs\\*, and\u002For have relapsed after allogeneic HSCT).\n\n     \\*Individuals that are CD19 positive will be considered for this study, However, these individuals should be ineligible for, unable to obtain in a timely manner, cannot access, unwilling to undergo, or have failed prior FDA approved CD19 CAR constructs.\n  4. Participants must have measurable or evaluable disease at the screening, defined by any evidence of MRD or positron emission tomography (PET)-avid extramedullary disease\n  5. Age \\>= 18 years\n  6. Clinical performance status: Karnofsky \\>= 50%. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.\n  7. Participants must have adequate organ and marrow function as defined below:\n\n     * Leukocytes \\>= 750\u002FmcL\\*\n     * Platelets \\>= 50,000\u002FmcL\\*\n     * Total bilirubin \\\u003C= 2 x upper limit of normal (ULN) (except in the case of participants with documented Gilbert s disease \\> 3 X ULN)\n     * Aspartate Aminotransferase (AST)\u002FAlanine Aminotransferase (ALT) \\\u003C= 5 X institutional ULN\n     * Creatinine \\\u003C 1.5X ULN OR Creatinine clearance \\>= 60 mL\u002Fmin\u002F1.73m\\^2 for participants with creatinine levels above max listed above\n\n       * A participant will not be excluded because of pancytopenia \\>=Grade 3 if it is due to underlying bone marrow involvement by leukemia\n  8. Cardiac function: left ventricular ejection fraction (LVEF) \\>=45% or fractional shortening \\>= 28%, and no clinically significant electrocardiogram (EKG) findings\n  9. Pulmonary Function: Baseline oxygen saturation \\> 92% on room air at rest without oxygen supplementation\n  10. Participants with the following central nervous system (CNS) status are eligible:\n\n      * CNS 1, defined as absence of blasts in CSF on cytospin preparation, regardless of the number of WBCs;\n      * CNS 2, defined as presence of \\\u003C 5\u002FmcL WBCs in CSF and cytospin positive for blasts, or \\> 5\u002FmcL WBCs but negative by Steinherz\u002FBleyer algorithm:\n\n        * CNS 2a: \\\u003C 10\u002FmcL red blood cells (RBCs); \\\u003C 5\u002FmcL WBCs and cytospin positive for blasts;\n        * CNS 2b: \\>=10\u002FmcL RBCs; \\\u003C 5\u002FmcL WBCs and cytospin positive for blasts;\n        * CNS 2c: \\>=10\u002FmcL RBCs; \\>= 5\u002FmcL WBCs and cytospin positive for blasts but negative by Steinherz\u002FBleyer algorithm.\n  11. Contraception:\n\n      * Women of child-bearing potential (WOCBP) must agree to use a highly effective contraception (hormonal, intrauterine device \\[IUD\\], surgical sterilization, abstinence) at the study entry and up to 12 months after the last dose of combined chemotherapy. Note: WOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.\n      * Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and for 4 months after the last dose of study drugs. We also will recommend men ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men able to father a child must not freeze or donate sperm within the same period.\n  12. Nursing participants must be willing to discontinue nursing from study treatment initiation through 1 month after the last dose of the study drug(s).\n  13. Ability and willingness of participant or Legally Authorized Representative (LAR) to co-enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.\n  14. Participant or LAR must understand and sign a written informed consent.\n\n      EXCLUSION CRITERIA:\n\n  \u003C!-- -->\n\n  1. Recurrent or refractory leukemia limited to isolated testicular or isolated CNS disease\n  2. CNS 3 disease including participants with radiologically detected active CNS lymphoma, or participants who have cranial nerve palsy from active CNS leukemia. Note: Chronic complications of prior CNS disease are not exclusionary in the absence of active disease (e.g., blindness from prior ocular CNS disease or persistent cranial nerve palsy)\n  3. Hyperleukocytosis (\\>=50,000 blasts\u002FmcL)\n  4. Positive serum or urine beta-human chorionic gonadotropin (beta-HCG) pregnancy test performed in WOCBP at screening.\n  5. Washout criteria (time prior to apheresis or prior to start of LD if apheresis is not done on this protocol):\n\n     ====\n\n     Therapy: Systemic chemotherapy, antineoplastic investigational agents, or antibody-based therapies, any investigational therapy\n\n     Washout\\*: \\>= 2 weeks\n\n     Exceptions: 6 weeks for clofarabine or nitrosoureas No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance type chemotherapy (vincristine, 6- mercaptopurine, oral methotrexate, or a tyrosine kinase for participants with Ph+ or Ph-like ALL) provided there is recovery from any acute toxic effects.\n\n     ====\n\n     Therapy: Radiation therapy\n\n     Washout\\*: \\>= 3 weeks\n\n     Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable\u002Fevaluable disease outside the radiation window.\n\n     ====\n\n     Therapy: History of allogeneic HSCT\n\n     Washout\\*: \\>=100 days since HSCT; \\>=30 days since completion of immunosuppression; \\>=6 weeks since donor lymphocyte infusion (DLI)\n\n     ====\n\n     Therapy: History of prior CAR therapy or other adoptive cell therapies\n\n     Washout\\*: \\> 30 days post infusion\n     * Time between prior therapy and apheresis or prior to start of LD if apheresis is not done on this protocol.\n  6. Human immunodeficiency virus (HIV) infection, as measured by seropositivity for HIV antibody.\n  7. Hepatitis B virus (HBV) infection, as measured by positivity for hepatitis B surface antigen (HbsAg).\n  8. Hepatitis C virus (HCV) infection, as measured by seropositivity for hepatitis C.\n  9. Active second malignancy with the exception of in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.\n  10. History of severe, immediate hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells.\n  11. Evidence of active graft-versus- host disease (GVHD).\n  12. Uncontrolled, symptomatic, intercurrent illness or social situations as evaluated by medical history, physical exam, and laboratory evaluations that would limit compliance with study requirements or would pose an unacceptable risk to the participant.",{"count":224,"type":22},57,[62],"Background:\n\nB-cell acute lymphoblastic leukemia (B-ALL) is a type of blood cancer. Some people with B-ALL have a gene mutation that makes the disease hard to treat. The mutation causes cancer cells to make too much of a protein called thymic stromal lymphopoietin receptor (TSLPR). Chimeric antigen receptor (CAR) T cell therapy is a treatment that takes immune cells (T cells) from a person s body and modifies them to attack specific proteins. Researchers want to test whether TSLPR-CART cells can be given safely to adults with forms of B-cell leukemia, and to learn whether the treatment may help fight these cancers.\n\nObjective:\n\nTo test TSLPR-CART in people with B-ALL.\n\nEligibility:\n\nPeople aged 18 years and older with B-ALL that did not respond or returned after treatment. They must have TSLPR on their B-ALL.\n\nDesign:\n\nParticipants will be screened. They will have imaging scans and tests of their heart function. Samples will be taken from their bone marrow. They will have a lumbar puncture: A needle will be inserted into their back to collect a sample of the fluid around the spinal cord.\n\nParticipants will undergo leukapheresis: Blood will be taken from their body through a tube. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different tube. The T cells will be used to create TSLPR-CART.\n\nParticipants will take chemotherapy over 5 days to prepare their body for the therapy; then they will receive the modified cells through a tube inserted into a vein. Staying in the hospital during part of the treatment is expected and participants will be monitored locally to evaluate for side effects. Approximately 1 month after receiving TSLPR-CART, participants will undergo evaluations to see how the TSLPR-CART impacted their leukemia. Participants will have follow-up visits for 2 years after TSLPR-CART either at NIH or at home....",[228,229],"B-All","Acute Lymphoblastic Leukemia",[231,232,229,228],"Adoptive Immunotherapy","CRLF2-R\u002FTSLPR Expressing Tumor",{"date":42,"type":43},{"date":45,"type":22},{"date":236,"type":22},"2032-06-30",{"name":49,"class":50},{"id":239,"slug":240,"hasResults":12,"nctId":241,"briefTitle":242,"officialTitle":243,"acronym":4,"eligibilityCriteria":244,"healthyVolunteers":12,"sex":17,"minAge":245,"maxAge":246,"enrollmentInfo":247,"targetDuration":4,"studyType":23,"phases":249,"briefSummary":250,"conditions":251,"keywords":256,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":261,"startDateStruct":262,"completionDateStruct":263,"leadSponsor":265,"locationsCount":51},"100633272","stem-cell-transplantation-for-participants-with-germline-runx1-associated-blood-cancers-100633272","NCT07524530","Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers","Phase II Haploidentical Hematopoietic Stem Cell Transplantation for Participants With Germline RUNX1 Associated Hematologic Malignancies","* INCLUSION CRITERIA:\n* Affected participants (Recipients)\n\n  * History of deleterious or suspected deleterious (defined as P\u002FLP or VUS with RUNX1 phenotype) germline RUNX1 mutation as defined by ClinVar (nih.gov)\n  * Histological confirmation of a myeloid malignancy - acute or chronic leukemia (\\\u003C5% marrow blasts preferred) or myelodysplastic syndrome\u002Fmyeloproliferative neoplasms (MDS\u002FMPN) (\\\u003C10% marrow blasts preferred). Participants may be treated on this study to achieve preferred blast cutoffs. Participants with poorly responsive or relapsed disease remain eligible and may proceed as the graft-versus-leukemia (GVL) effect may produce cures.\n\nSubjects requiring standard therapies to prepare for HCT should ideally be referred to this study in remission, if possible. However, sometimes disease status changes during evaluation for HCT and it is necessary to establish disease control through the administration of standard therapies during evaluation for HCT. If ongoing therapy for the underlying disease outside of the NIH is not in the best interest of the subject according to the clinical judgment of the NIH PI, then the subject may receive standard treatment for his\u002Fher underlying hematologic malignancy as a bridge to HCT on this protocol, prior to starting the research phase of the study. If it becomes apparent that the subject will not be able to proceed to HCT, then he\u002Fshe must come off study. Subjects receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol.\n\n* Availability of a haploidentical donor (HLA-match only).\n* Age \\>= 4 and \\\u003C= 70 years\n* Karnofsky (\\>=16 years) or Lansky (\\\u003C16 years) \\>=60%\n* For human immunodeficiency virus (HIV)-infected participants, participant must be on effective anti-retroviral therapy, without uncontrolled opportunistic infection and have approval via Transplant Infectious Disease consultation. Consider donor with CCR5(delta)32 homozygosity for these participants.\n* For individuals with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load (VL) must be undetectable on suppressive therapy, if indicated.\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV VL.\n* Contraception as follows:\n\n  ---Women of child-bearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \\[IUD\\], abstinence, surgical sterilization) at the study entry and up to and 12 months post conditioning and\u002For post-transplant.\n* Men that can father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 12 months posttransplant or 4 months after conditioning if transplant is not done. We also will recommend men that can father children with partners that can bear children ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men that can father children must not freeze or donate sperm within the same period.\n* Breastfeeding participants must be willing to discontinue breastfeeding during the study and for 12 months post-transplant or 1 week after conditioning if transplant is not done.\n* Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH (30 minutes drive), for a minimum of 100 days after transplant or longer if there are complications. The participants must commit to having an adult caregiver with them during the first 100 days after the transplant\n* Participants or parent\u002Fguardian\u002Flegally authorized representative must be able to understand and willing to sign a written informed consent document.\n* Additional criteria for recipients suitable for MAC\n\n  * Age \\\u003C= 65 years\n  * HCT-CI \\\u003C4\n  * Pulmonary function tests (PFTs): Forced expiratory volume in the first second (FEV1) and adjusted diffusion capacity of carbon monoxide (DLCO) \\>=66%, without dyspnea at rest or oxygen requirement. If too young to cooperate with PFTs, must have \\>=92% oxygen saturation on room air and no dyspnea at rest.\n  * Left ventricular ejection fraction (LVEF) \\>=50% by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan (101)\n  * Recipients must have adequate organ function as defined below:\n\n    * Total bilirubin \\\u003C1.5 x institutional upper limit of normal (iULN) (unless Gilbert disease, hemolysis)\n    * Aspartate aminotransferase (AST) \u002F Alanine aminotransferase (ALT) \\\u003C=2.5 x iULN (unless therapy related and will improve in discussion with the National Institute of Diabetes and Digestive and Kidney Diseases \\[NIDDK\\])\n    * Creatinine within normal institutional limits or 24-hour urine or calculated creatinine clearance \\>=60 mL\u002Fmin\u002F1.73 m\\^2 for individuals with creatinine levels above institutional normal (calculated using the Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\] equation)\n* Additional criteria for recipients suitable for RIC\n\n  * Age \\\u003C=70 years\n  * PFTs: FEV1 and DLCO \\>=50%, without dyspnea at rest or oxygen requirement. If too young to cooperate with PFTs, must have \\>=92% oxygen saturation on room air and no dyspnea at rest\n  * LVEF \\>=40% by ECHO or MUGA obtained within 2 months of HSCT (Children s Oncology Group \\[COG\\] criteria).\n  * Recipients must have adequate organ function as defined below:\n\n    * Total bilirubin \\\u003C2.5 x iULN (unless Gilbert disease, hemolysis)\n    * AST\u002FALT \\\u003C3.5 x iULN (unless therapy related and will improve in discussion with NIDDK)\n    * Creatinine within normal institutional limits or 24-hour urine or calculated creatinine clearance \\>=50 mL\u002Fmin\u002F1.73 m\\^2 for individuals with creatinine levels above institutional normal (calculated using the CKD-EPI equation)\n* Unaffected participants\n\n  * Haploidentical donors\n\n    ----Age \\>=4 years\n  * Participants or parent\u002Fguardian must be able to understand and willing to sign a written informed consent document.\n  * Unaffected family members\n\n    * Age \\>=18 years\n    * If the participant is a blood relative of the recipient, participant must be negative for RUNX1 mutations by molecular testing\n    * Participants must be able to understand and willing to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n-All participants\n\n* Recipients who are receiving any investigational agent except virus specific T cells (VST)\n* Active non-hematologic malignancies\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in study.\n* Participants with the following cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (except atrial fibrillation if cleared by cardiology consultation)\n* Participants without access to medical care at home.\n* Positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test at screening\n* Uncontrolled intercurrent illness evaluated by history, physical exam, and laboratory studies or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant","4 Years","70 Years",{"count":248,"type":22},98,[25],"Background:\n\nSome blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate.\n\nObjective:\n\nThe primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical\u002Fexpected disease free survival.\n\nEligibility:\n\nPeople aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers.\n\nDesign:\n\nParticipants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken.\n\nA flexible tube (central line) will be inserted into a vein in participants chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge.\n\nParticipants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line.\n\nAfter discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years.\n\nDonors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.",[252,253,254,255],"Core Binding Factor Alpha Subunits","Hematologic Neoplasms","Leukemia","Lymphoma",[257,258,259,260],"RUNX1","Haploidentical Hematopoietic Stem Cell Transplant","Germline RUNX1","germline RUNX1-aassociated myeloid malignancy",{"date":42,"type":43},{"date":45,"type":22},{"date":264,"type":22},"2036-06-01",{"name":49,"class":50},{"id":267,"slug":268,"hasResults":12,"nctId":269,"briefTitle":270,"officialTitle":271,"acronym":4,"eligibilityCriteria":272,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":273,"targetDuration":4,"studyType":23,"phases":275,"briefSummary":276,"conditions":277,"keywords":281,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":286,"startDateStruct":287,"completionDateStruct":288,"leadSponsor":290,"locationsCount":51},"100632080","autologous-b7-h3-chimeric-antigen-receptor-t-cells-in-previously-treated-extensive-stage-small-cell-lung-cancer-with-recurrent-or-refractory-disease-100632080","NCT07509034","Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease","A Phase I Study to Assess the Safety and Antitumor Activity of Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease","* INCLUSION CRITERIA:\n* Age \\>=18 years old.\n* Histologically confirmed small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that has recurred following or is refractory to first-line therapy. Note: small cell cancers of non-lung primary sites are also eligible.\n* Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.\n* Pulse oximetry \\>= 90% on room air.\n* Aspartate Transferase (AST) \\\u003C 3 X institutional upper limit of normal (ULN). Note: in case of liver metastases \\\u003C= 5 X ULN is acceptable.\n* Alanine Aminotransferase (ALT) \\\u003C 3 X institutional ULN. Note: in case of liver metastases \\\u003C= 5 X ULN is acceptable.\n* Total bilirubin \\\u003C=2 X institutional ULN.\n* Creatinine \\\u003C=1.5 X institutional ULN OR creatinine clearance (CrCl) \\>= 50 mL\u002Fmin\u002F1.73m\\^2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\] formula or calculated eGFR provided by a laboratory).\n* Absolute Neutrophil Count (ANC) \\>= 750\u002FmcL.\n* Platelet count \\>= 75,000\u002FmcL.\n* An absolute lymphocyte count (ALC) \\>=300\u002FmcL and CD3+ cell count \\>=150\u002FmcL.\n* Normal cardiac ejection fraction as defined by \\>= 45% by echocardiogram (ECHO) at screening.\n* At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 that has not been previously irradiated.\n* Recovered from acute toxic effects of all prior cancer therapy to Grade \\\u003C2 per Common Terminology Criteria for Adverse Events (CTCAE) v.6.0 at least one week before apheresis excluding the parameters for ANC and ALC mentioned above.\n* The following criteria must be met prior to apheresis:\n\n  * Chemotherapy and biologic\u002Ftargeted agents:\n\n    * \\>=14 days since the last dose of standard myelosuppressive chemotherapy.\n    * \\>= 7 days since the completion of biologic agent, targeted agent, or tyrosine kinase inhibitor therapy.\n    * \\>= 3 weeks or 5 half-lives (whichever is shorter) since prior therapy with a monoclonal antibody.\n  * Radiotherapy:\n\n    * \\>= 1 week since the last radiotherapy session.\n    * No washout period required for palliative radiation to non-target lesions.\n    * \\>= 3 weeks since hepatic radiation, chemoembolization, and\u002For radiofrequency ablation.\n  * Steroids and immunosuppressive therapy:\n\n    * Corticosteroids: \\>= 2 weeks since the therapeutic doses (\\> 0.5 mg\u002Fkg\u002Fday prednisone or equivalent). Note: Inhaled or topical steroids are not exclusionary.\n    * Physiologic replacement doses (up to 5 mg\u002Fday prednisone equivalent) are allowed and can be adjusted based on participant's BMI if warranted.\n    * \\>= 2 weeks since the other immunosuppressive medication (e.g., calcineurin inhibitors, methotrexate, rapamycin, thalidomide, etc.).\n  * Anti-PD-1 and any investigational therapies:\n\n    * \\>= 2 weeks since Anti-PD-1 monoclonal antibody therapy.\n    * \\>= 2 weeks or 5 half-lives of the investigational product (whichever is shorter) since any investigational treatment or clinical trial participation.\n  * Other criteria:\n\n    * 72 hours since small molecule tyrosine kinase inhibitors (e.g., EGFR inhibitors), PARP inhibitors, or KRAS G12C inhibitors.\n* Individuals of childbearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \\[IUD\\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy.\n\nNote: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.\n\n* Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 7 months after the last dose of study drugs. We also will recommend individuals able to father a child with partners of childbearing potential ask partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period.\n* Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s).\n* Ability of the participant to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* History of anaphylactic reactions attributed to anti-B7-H3 antibodies or compounds of similar chemical or biologic composition to autologous B7-H3 CAR T cells, cyclophosphamide, fludarabine, or other agents used in this study.\n* Infection exposure with the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as defined below:\n\n  * Positive serology for HIV.\n  * Active HBV infection as demonstrated by test for hepatitis B surface antigen (HBsAg).\n  * Positive serology for HCV.\n* Prior gene therapy using an integrating vector (except for autologous B7-H3 CAR T cells retreatment).\n* History of any previous allogeneic hematopoietic stem cell transplant.\n* Presence of fungal, bacterial, viral, or other infection is permitted if responding to active treatment.\n* Central Nervous System (CNS) disorder such as cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that may impair the ability to evaluate neurotoxicity.\n* Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP at screening.\n* Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history, physical exam, electrocardiogram (ECG) or situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.",{"count":274,"type":22},40,[62],"Background:\n\nSmall cell lung cancer (SCLC) is the deadliest form of lung cancer. Extrapulmonary neuroendocrine cancer (EPNEC) is a similar type of cancer that develops anywhere other than the lungs. EPNEC is also deadly. B7-H3 is a protein often found in SCLC and EPNEC tumor cells. Researchers can modify a person s own T cells, or immune cells, to target B7-H3. When these modified T cells are returned to the body-a treatment called B7-H3 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells.\n\nObjective:\n\nTo test B7-H3 CAR T cell therapy in people with SCLC or EPNEC.\n\nEligibility:\n\nPeople aged 18 years and older with SCLC or EPNEC that either did not respond or returned after treatment.\n\nDesign:\n\nParticipants will be screened. They will have blood tests and tests of their heart function. They will have imaging scans.\n\nParticipants will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be altered to make them attack cells with B7-H3.\n\nParticipants will be in the hospital for at least 15 days. They will receive chemotherapy drugs to prepare their body for the treatment. These drugs will be given through a tube attached to a needle inserted into a vein.\n\nThe modified T cells will be infused through a vein. Participants will remain in the hospital until they are well enough to go home.\n\nFollow-up visits will continue for 15 years....",[278,279,280,156],"Extensive-Stage Small Cell Lung Cancer","Extrapulmonary Neuroendocrine Carcinoma","Recurrent or Refractory",[282,283,284,285],"B7-H3","CAR-T","Phase I","Immunotherapy",{"date":42,"type":43},{"date":45,"type":22},{"date":289,"type":22},"2031-01-30",{"name":49,"class":50},{"id":292,"slug":293,"hasResults":12,"nctId":294,"briefTitle":295,"officialTitle":295,"acronym":4,"eligibilityCriteria":296,"healthyVolunteers":12,"sex":17,"minAge":297,"maxAge":19,"enrollmentInfo":298,"targetDuration":4,"studyType":199,"phases":4,"briefSummary":300,"conditions":301,"keywords":307,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":314,"startDateStruct":315,"completionDateStruct":316,"leadSponsor":318,"locationsCount":51},"100630569","nci-childhood-cancer-data-initiative-ccdi-led-pediatric-adolescent-and-young-adult-rare-cancer-registry-for-very-rare-solid-tumors-100630569","NCT07489378","NCI Childhood Cancer Data Initiative (CCDI) Led Pediatric, Adolescent, and Young Adult Rare Cancer Registry for Very Rare Solid Tumors","* INCLUSION CRITERIA:\n* History of newly diagnosed (within 1 year of diagnosis) very rare solid tumor (defined as an estimated 2 incident cases per million per year).\n* Age \\>= 1 month and \\\u003C= 39 years at the time of diagnosis.\n* Participants must have established care with a local treating physician.\n* Ability of the participant, parent\u002Fguardian, or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n* Diagnosis of any of the following at any time:\n\n  * Ewing Sarcoma\n  * Osteosarcoma\n  * Rhabdomyosarcoma\n  * Diffuse midline glioma (H3K27 altered)\n  * Atypical teratoid rhabdoid tumor\n  * Pleuropulmonary blastoma\n  * Common adult cancers that occur in pediatric\u002FAYA populations (i.e., colorectal cancer, breast cancer)\n* The participant is unlikely to comply with the terms of the protocol.","1 Month",{"count":299,"type":22},4000,"Background:\n\nAll childhood cancers are rare, but some are called very rare. Very rare cancers are diagnosed in 2 or fewer out of 1 million people each year. Researchers want to gather data so they can learn more about these very rare cancers. They hope to use the data to develop future treatments.\n\nObjective:\n\nTo gather data for a registry of very rare cancers found in children, teens, and young adults.\n\nEligibility:\n\nPeople aged 1 month to 39 years newly diagnosed (within the past year) with a very rare cancer.\n\nDesign:\n\nParticipation will be by phone or email. No clinic visits are required.\n\nResearchers will look at the participant s medical records. They will ask for samples of tumor tissue that were already removed. They will use the samples for genetic testing. The results of these tests will be sent to the participant s own doctors.\n\nSome participants will be asked for saliva or cheek swab samples. They will receive a kit in the mail. They will spit into a tube or swab the inside of their cheek. They will mail the sample back to the lab.\n\nParticipants will fill out questionnaires once a year for 5 years. They will answer questions about:\n\nFamily history, such as other cancers in the family and their income, work, and education.\n\nDemographics, such as their gender, nationality, ethnicity, education, and work history.\n\nSymptoms and treatment for their cancer. This may include level of pain, and emotional and physical well-being.\n\nParticipants data will be added to a secure database for other researchers. Their data will be anonymous.",[302,303,304,305,306],"Very Rare Tumors","Very Rare Cancers","Other Solid Tumors","Solid Tumor","Pediatric Rare Tumors",[308,309,310,311,312],"Longitudinal Study","Registry","Patient Reported Outcomes","Family History","Molecular Characterization","RECRUITING",{"date":42,"type":43},{"date":45,"type":22},{"date":317,"type":22},"2037-04-01",{"name":49,"class":50},{"id":320,"slug":321,"hasResults":12,"nctId":322,"briefTitle":323,"officialTitle":324,"acronym":4,"eligibilityCriteria":325,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":326,"targetDuration":4,"studyType":23,"phases":328,"briefSummary":330,"conditions":331,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":337,"startDateStruct":338,"completionDateStruct":340,"leadSponsor":342,"locationsCount":343},"100623064","testing-whether-hormone-therapy-with-ribociclib-is-as-effective-as-chemotherapy-followed-by-hormone-therapy-with-ribociclib-for-the-treatment-of-high-anatomic-stage-breast-cancer-with-low-recurrence-risk-the-rxfine-low-trial-100623064","NCT07391774","Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial","A Phase III Trial of Rx Therapy Guided by Genomic Risk Assessment For High Anatomic Stage ER-pos\u002FHER2-neg Breast Cancer With RS Less Than or Equal to 25 (RxFINE-Low)","Inclusion Criteria:\n\n* STEP 0: Patient must be ≥ 18 years of age\n* STEP 0: Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days prior to Step 0 pre-registration\n* STEP 0: Patient must be a postmenopausal woman or a man\n\n  * NOTE: Menopause can be determined by any of the following:\n\n    * Prior bilateral oophorectomy\n    * Age ≥ 60 years\n    * Age \\\u003C 60 years with amenorrhea for ≥ 12 months and estradiol and follicle stimulating hormone (FSH) levels in the postmenopausal range\n  * NOTE: FSH and estradiol levels should be repeated as clinically indicated to ensure menopausal status in patients with breast cancer with chemotherapy-induced amenorrhea\n* STEP 0: Patient must meet one of the following staging criteria postoperatively according to American Joint Committee on Cancer (AJCC) 8th edition criteria\n\n  * pT0-T3 with 3 positive ipsilateral lymph nodes (micro-or macrometastatic disease) and no planned axillary lymph node dissection after definitive surgery in the breast and axilla with curative intent.\n  * pT0-T3 with N2 or N3\n  * pT3 with N0-N3\n\n    * NOTES:\n\n      * Patients with T4 breast cancer are not eligible.\n      * Positive isolated tumor cells (ITCs) in axillary nodes without micro- or macrometastasis are considered N0 for eligibility purposes.\n      * ITC does not contribute to nodal count for staging purposes\n* STEP 0: Patient must have a primary breast tumor that is estrogen receptor (ER) positive with \\> 10% ER expression by immunohistochemistry (IHC) as per 2020 American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) Estrogen Receptor Testing Guideline.\n\n  * NOTE: ER 1-10% are reported as ER low positive. These tumors have less endocrine-sensitive disease and are not eligible)\n* STEP 0: Patient must have a primary breast tumor that is HER2-negative by current ASCO\u002FCAP guidelines utilizing immunohistochemistry and\u002For fluorescence in situ hybridization (FISH)\n* STEP 0: Patient may have multicentric or multifocal breast cancer if the highest stage tumor meets eligibility criteria outlined above, and the tumor sites are felt to represent a single disease process by local pathology or other sites of disease are also ER-positive (\\> 10%) and HER2 negative, if such testing is completed. If local pathology feels that multicentric or multifocal disease may represent distinct disease processes repeat disease receptor testing is required other sites of disease must also be also ER-positive (\\> 10%) and HER2-negative\n* STEP 0: For patients who have undergone a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection\n* STEP 0: For patients who have undergone mastectomy, the margins must be free of residual gross tumor. Patients with microscopic positive margins are eligible if post-mastectomy radiation treatment (RT) of the chest wall will be administered\n* STEP 0: Patient must have undergone axillary staging with sentinel lymph node biopsy (SLNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND)\n* STEP 0: Patient must have no evidence of locoregional or distant metastatic disease by clinical history and physical exam. Treating physician can consider additional imaging evaluation per National Comprehensive Cancer Network (NCCN) guidelines and\u002For institutional practice\n* STEP 0: Patient must be able to have Oncotype DX testing performed.\n\n  * If Oncotype DX testing was previously performed, the results of Recurrence Score (RS) must be available and must meet Step 1 eligibility criteria.\n  * If Oncotype DX testing was not performed yet, tissue from the core, excisional biopsy or surgical specimen of the tumor lesion must be available and must be shipped to Exact Sciences for determination of the Oncotype DX Recurrence Score (RS) for eligibility and stratification.\n\n    * NOTE: Exact Sciences will notify the submitting institution of Recurrence Score results within two (2) weeks of receipt of the tumor specimen. Institutions will receive an email notification of eligibility status once Recurrence Score results are entered into Rave by the submitting institution\n* STEP 0: Patient must have had their final cancer surgery for breast cancer (including re-excision of margins) less than 16 weeks prior to Step 0 Pre-Registration.\n\n  * NOTE: This excludes additional surgery for reconstructive purposes\n* STEP 0: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* STEP 0: Patients with synchronous DCIS or LCIS are eligible\n* STEP 0: Patient with prior history of ER-negative DCIS diagnosed at least 5 years prior to Step 0 Pre-Registration without evidence of recurrence are eligible\n* STEP 0: Patient must not have a prior history of invasive ER-positive breast cancer. Patients with a history of ER-negative breast cancer are eligible if they were diagnosed at least 5 years prior to Step 0 Pre-Registration and have had no evidence of recurrence\n* STEP 0: Patients must not have received prior endocrine therapy such as tamoxifen, raloxifene, or aromatase inhibitors for chemoprevention within 5 years prior to Step 0 Pre-Registration with the exception of a short course of endocrine therapy of less than 6 weeks duration prior to Step 0 Pre-Registration.\n\n  * NOTE: The Oncotype DX for study eligibility must be performed on specimen obtained prior to initiation of any endocrine therapy\n* STEP 0: Patient must not be concurrently using systemic hormone replacement therapy (HRT). If receiving HRT at the time of breast cancer diagnosis, this must be discontinued prior to Step 0 Pre-Registration with appropriate washout\n* STEP 0: Absolute neutrophil count (ANC) ≥ 1,500\u002FµL (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Hemoglobin ≥ 9.0 g\u002FdL (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Platelets ≥ 100,000\u002FµL (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Total bilirubin ≤ institutional upper limit of normal (ULN) or \\\u003C 1.5 x ULN for patients who have a bilirubin elevation in patients with well documented Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 2.5 × institutional ULN (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Estimated glomerular filtration rate (eGFR) ≥ 30 mL\u002Fminute\u002F1.73 m\\^2 (obtained ≤ 28 days prior to Step 0 Pre-Registration)\n* STEP 0: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 0 Pre-Registration are eligible for this trial\n* STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* STEP 0: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* STEP 0: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better\n* STEP 0: Patient must have a standard 12-lead electrocardiogram (ECG) within 28 days prior to Step 0 Pre-Registration, documenting:\n\n  * QT interval using Fridericia's correction (QTcF) \\\u003C 450 msec.\n  * Resting heart rate 50-90 beats per minute (determined from the ECG)\n* STEP 0: Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and\u002For family member available will also be considered eligible\n* STEP 0: Patient must not have comorbidities considered a safety risk for standard adjuvant chemotherapy, endocrine therapy or CDK4\u002F6 inhibitor as per Investigator's discretion\n* STEP 0: Patient must not have a contraindication to adjuvant chemotherapy based on treating physician's discretion\n* STEP 0: Patient must not have received prior chemotherapy for this malignancy\n* STEP 0: Patient must not have received prior CDK4\u002F6 inhibitor\n* STEP 0: Patient must not have a known contraindication to ribociclib per current Food and Drug Administration (FDA) indication\n* STEP 0: Patient must not have a known hypersensitivity to any of the excipients of ribociclib and\u002For endocrine therapy (ET) (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy)\n* STEP 0: Males must not expect to father children and males and their partners must be willing to use highly effective methods of contraception while on protocol treatment. Males must not donate sperm while on protocol treatment and for at least 12 weeks following the last dose of protocol treatment.\n\nHighly effective methods include the following:\n\n* Intrauterine device\n* Bilateral tubal occlusion\n* Vasectomized partner\n* Sexual abstinence If the highly effective contraceptive methods are contraindicated or strictly declined by the patient, or in the event of sexual activity of low frequency, a combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier methods) is also considered an acceptable birth control method. Local regulation\u002Fguidelines are to be followed with regard to highly effective birth control method, if more restrictive\n\n  * STEP 1: Patient must meet all Step 0 Pre-Registration eligibility criteria at the time of their Step 1 randomization\n  * STEP 1: Patient must not have had any major surgery or radiotherapy within 14 days prior to Step 1 randomization\n  * STEP 1: Patient must have a Recurrence Score (RS) of 0-25 from Oncotype DX testing from diagnostic biopsy or surgical specimen as reported by the Exact Sciences assay",{"count":327,"type":22},1978,[329],"PHASE3","This phase III trial compares standard of care hormone therapy plus ribociclib to chemotherapy followed by hormone therapy plus ribociclib for the treatment of patients with high anatomic stage breast cancer with low risk of the cancer returning (low risk recurrence). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy, with letrozole, anastrozole or exemestane, lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hormone therapy plus ribociclib may work as well as chemotherapy followed by hormone therapy plus ribociclib for the treatment of high anatomic stage breast cancer with low recurrence risk.",[332,333,334,335,336],"Anatomic Stage II Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Estrogen Receptor-Positive Breast Carcinoma","HER2-Negative Breast Carcinoma",{"date":42,"type":43},{"date":339,"type":43},"2026-08-10",{"date":341,"type":22},"2029-07-31",{"name":49,"class":50},140,{"id":345,"slug":346,"hasResults":12,"nctId":347,"briefTitle":348,"officialTitle":349,"acronym":4,"eligibilityCriteria":350,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":351,"targetDuration":4,"studyType":23,"phases":353,"briefSummary":354,"conditions":355,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":358,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":364},"100618506","testing-the-effect-of-teclistamab-on-recurrent-plasmablastic-lymphoma-100618506","NCT07332507","Testing the Effect of Teclistamab on Recurrent Plasmablastic Lymphoma","Phase 1b Study of Teclistamab in Relapsed\u002FRefractory Plasmablastic Lymphoma","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed R\u002FR PBL\n* Patients must have measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as ≥ 1.0 cm in its longest dimension\n* Patients should have ≥ 1 line of prior therapy. This includes at least 1 prior line of chemotherapy or radiation\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of teclistamab in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Hemoglobin ≥ 8 g\u002FdL, transfusion permitted if ≥ 7 days\n* Absolute neutrophil count ≥ 1,000\u002FmcL\n* Platelets ≥ 75,000\u002FmcL\n* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN\n* Glomerular filtration rate (GFR) ≥ 30 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with central nervous system (CNS) lymphoma are eligible if they have no CNS-related symptoms at study entry, and the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients should either have received an autologous transplant or not be a candidate for one\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* Based on the mechanism of action, teclistamab may cause fetal harm when administered to a pregnant woman. Females of child-bearing potential (FCBP) should use effective contraception during treatment with teclistamab and for 6 months after the last dose. FCBP should not breast feed during treatment with teclistamab and for 6 months after the last dose. Should a FCBP become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with a partner who is a FCBP should use effective contraception during treatment and for 3 months after the last dose of teclistamab. Women of childbearing age should not donate eggs and men should not donate sperm for the duration of study participation. Women should not donate eggs for 6 months and men should not donate sperm for 3 months after completion of the last dose of study drug\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n* Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment and at least 4 weeks after treatment\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and peripheral neuropathy\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to teclistamab\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because teclistamab is a bispecific T-cell antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with teclistamab, breastfeeding should be discontinued if the mother is treated with teclistamab. These potential risks may also apply to other agents used in this study\n* Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation\n* Corticosteroid use for purposes other than lymphoma symptom control\n\n  * The use of inhaled corticosteroids is permitted\n  * The use of mineralocorticoids for management of orthostatic hypotension is permitted\n  * The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted\n  * Participants who require lymphoma symptom control during screening may receive steroids in the following manner:\n\n    * Up to 100 mg\u002Fday of prednisone or equivalent may be used for lymphoma symptom control during screening\n* Prior treatment with B-cell maturation antigen (BCMA)-targeted therapies\n* Prior treatment with T-cell engager therapies (bispecific, CAR-T, etc.) within the last 6 months",{"count":352,"type":22},30,[62],"This phase Ib trial tests the safety, side effects, and best dose of teclistamab in treating patients with plasmablastic lymphoma that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen (BCMA), a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving teclistamab may be safe and tolerable in treating patients with recurrent or refractory plasmablastic lymphoma.",[356,357],"Recurrent Plasmablastic Lymphoma","Refractory Plasmablastic Lymphoma",{"date":42,"type":43},{"date":360,"type":22},"2027-03-26",{"date":362,"type":22},"2027-12-31",{"name":49,"class":50},4,{"id":366,"slug":367,"hasResults":12,"nctId":368,"briefTitle":369,"officialTitle":370,"acronym":4,"eligibilityCriteria":371,"healthyVolunteers":12,"sex":372,"minAge":18,"maxAge":4,"enrollmentInfo":373,"targetDuration":4,"studyType":23,"phases":375,"briefSummary":376,"conditions":377,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":380,"startDateStruct":381,"completionDateStruct":383,"leadSponsor":385,"locationsCount":374},"100608170","testing-the-addition-of-an-antiangiogenic-drug-bevacizumab-to-chemotherapy-carboplatin-and-paclitaxel-combined-with-immunotherapy-pembrolizumab-for-pmmr-tp53-mutated-endometrial-cancer-100608170","NCT07198074","Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer","A Randomized Phase III Trial of Carboplatin, Paclitaxel, Pembrolizumab Versus Carboplatin, Paclitaxel, Bevacizumab Versus Carboplatin, Paclitaxel, Pembrolizumab, Bevacizumab in the Treatment of pMMR, TP53 Mutated Advanced or Recurrent Endometrial Cancer","Inclusion Criteria:\n\n* Documentation of disease:\n\n  * Stage III and stage IVA endometrial cancers (with measurable disease),\n  * Stage IVB endometrial cancer (with or without measurable disease), or\n  * Recurrent endometrial cancer (with or without measurable disease)\n* In patients with measurable disease, lesions will be defined and monitored by RECIST 1.1. Measurable disease (RECIST 1.1) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI\n* Histologic confirmation of the original primary tumor is required (submission of pathology report\\[s\\] is required). Patients with the following histologic types are eligible: endometrioid, serous, dedifferentiated\u002Fundifferentiated, clear cell, mixed epithelial, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.)\n* Patients must have:\n\n  * Tumoral mismatch repair proficient (pMMR) disease as assessed by immunohistochemistry (IHC) AND\n  * P53 IHC with aberrant staining pattern (aberrant p53 expression is consistent with mutant TP53). TP53 mutation by next-generation sequencing will also be accepted\n* A pathology report demonstrating results of institutional MMR IHC and p53 IHC and\u002For TP53 by next-generation sequencing\n* Patients may have received:\n\n  * NO prior chemotherapy for treatment of endometrial cancer OR\n  * Prior adjuvant chemotherapy (e.g., paclitaxel\u002Fcarboplatin alone or as a component of concurrent chemotherapy and radiation therapy \\[with or without cisplatin\\]) provided adjuvant chemotherapy was completed ≥ 12 months prior to registration\n* Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic\u002Fpara-aortic radiation therapy, intravaginal brachytherapy, and\u002For palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to registration. For patients with recent radiation, they must have RECIST-evaluable disease outside of the radiation field and have recovered their marrow function\n* Patients may have received prior hormonal (endocrine) therapy. All hormonal (endocrine) therapy must have been completed at least 1 week prior to registration\n* NO prior pembrolizumab (or other anti-PD1, anti-PDL1 or anti-CTLA4 therapy) or bevacizumab (or other antiangiogenic therapy)\n* Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids\n* Age ≥ 18\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2\n* Not pregnant and not nursing\n* Absolute neutrophil count (ANC) ≥ 1,500 cells\u002Fmm\\^3\n* Platelets ≥ 100,000 cells\u002Fmm\\^3\n* Hemoglobin ≥ 8 g\u002Fdl\n* Creatinine clearance (CrCl) of ≥ 30 mL\u002Fmin by the Cockcroft-Gault formula\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* No active infection requiring parenteral antibiotics\n* No current evidence of intra-abdominal abscess, abdominal\u002Fpelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and\u002For need for drainage nasogastric or gastrostomy tube\n* No clinically significant bleeding within 28 days prior to registration\n* No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg\n* No major surgery within 28 days of initiation of bevacizumab\n* No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease\n\n  * Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible\n  * Topical or inhaled steroids are allowed\n  * Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), and anti-thyroid antibodies should be evaluated with the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible\n* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis\n* No history of stem cell or solid organ transplant\n* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)","FEMALE",{"count":374,"type":22},255,[329],"This phase III trial compares the effect of bevacizumab in combination with carboplatin, paclitaxel and pembrolizumab to the usual treatments of carboplatin and paclitaxel with or without pembrolizumab in treating patients with stage III, IVA or IVB mismatch repair protein proficient (pMMR) and TP53 mutated endometrial cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has come back after a period of improvement (recurrent). Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adding bevacizumab to the combination of carboplatin, paclitaxel and pembrolizumab may be more effective than the usual treatment combinations of carboplatin and paclitaxel with or without pembrolizumab in treating patients with advanced or recurrent pMMR and TP53 mutated endometrial cancer.",[378,379],"Advanced Endometrial Carcinoma","Recurrent Endometrial Carcinoma",{"date":42,"type":43},{"date":382,"type":43},"2026-01-27",{"date":384,"type":22},"2028-07-01",{"name":49,"class":50},{"id":387,"slug":388,"hasResults":12,"nctId":389,"briefTitle":390,"officialTitle":391,"acronym":4,"eligibilityCriteria":392,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":393,"enrollmentInfo":394,"targetDuration":4,"studyType":23,"phases":396,"briefSummary":397,"conditions":398,"keywords":400,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":405,"startDateStruct":406,"completionDateStruct":408,"leadSponsor":410,"locationsCount":51},"100605401","phase-1-phase-i-trial-integrating-hla-haploidentical-anti-cd19-car-t-cells-with-post-transplantation-cyclophosphamide-based-hla-haploidentical-hematopoietic-cell-transplantation-100605401","NCT07162038","Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR-T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation","Phase I Trial Integrating HLA-Haploidentical Anti-CD19 CAR T Cells With Post-Transplantation Cyclophosphamide-Based HLA-Haploidentical Hematopoietic Cell Transplantation","-INCLUSION CRITERIA - Recipient\n\n1. Participants with high or very high-risk hematologic malignancies, as defined by the revised Disease Risk Index (DRI), or malignancy that remains persistently MRD+ (by flow cytometry, cytogenetics, FISH, PCR, or NGS) on most recently assessed disease specimen (within 2 months of initiating conditioning).\n2. Hematologic malignancy must be CD19+ (uniform expression on immunohistochemistry or \\>= 80% on flow cytometry) as confirmed by CD19 IHC assay (BT51E) or flow cytometry (BD QuantiBRITE(TM) Beads PE Fluorescence Quantitation Kit). (Participants do not have to have refused or lack access to commercial anti-CD19 CAR-T-cell therapies since this study focuses on the integration of CAR-T cells and HCT and not specifically the CAR-T cells themselves; furthermore the construct used to manufacture this product is the same as used in a current commercial product, but developed from a new batch and with a similar but not identical manufacturing process.)\n3. Age 18-75\n4. Karnofsky \\>= 60%.\n5. Participants must have adequate organ and marrow function as defined below:\n\n   * Cardiac ejection fraction \\>= 45% by 2D echocardiography;\n   * Forced expiratory volume-1 (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of \\>=50% predicted (this requirement would be waived in participants who are unable to properly perform pulmonary function tests - in such circumstances, participants must have pulse oximetry \\>=90% on room air and no dyspnea or obvious pulmonary restrictions);\n   * Estimated serum creatinine clearance of \\>= 60 ml\u002Fminute\u002F1.73m\\^2 calculated using eGFR in the clinical lab (participants with estimated serum creatinine clearance less than 60 may have measured creatinine clearance performed and if \\>= 60 will be considered eligible);\n   * Total bilirubin \\\u003C= 2X the upper limit of normal (participants with documented or suspected Gilbert s are exempt from this requirement);\n   * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \\\u003C= 5X the upper limit of normal.\n6. At least one available HLA-haploidentical donor\n7. Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization, abstinence) at the study entry and for 1 year after transplant (restriction period).\n\n   Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and for 1 year after transplant. We also will recommend men with female partners of childbearing potential to ask female partners to be on highly effective birth control (hormonal, intrauterine device (IUD), surgical sterilization). Men must not freeze or donate sperm within the same period.\n8. Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 1 year after transplant.\n9. Participants seropositive for human immunodeficiency virus (HIV) not due to intravenous immunoglobulin, must have adequate viral suppression (HIV viral load \\\u003C 200 viral copies per ml of blood) prior to the beginning of conditioning.\n10. For participants seropositive for hepatitis B virus (HBV) core antibody not due to intravenous immunoglobulin, a HBV viral load should be undetectable.\n11. Participants seropositive for hepatitis C virus (HCV) not due to intravenous immunoglobulin must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n12. Ability of participant or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document.\n13. Ability and willingness of participant to co-enroll on 20-C-0051: Gene Therapy Follow Up Protocol for Subjects Previously Enrolled in NCI for Immuno-Oncology Studies\n\n14 Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH (\\\u003C60 minutes drive), for a minimum of 100 days after transplant or longer if there are complications. Participants must commit to having an adult caregiver with them during the first 100 days after transplant in case of discharging from the hospital before 100 days.\n\nINCLUSION CRITERIA - Donor\n\n1\\. Related donor (age \\>=12) deemed suitable, eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood, bone marrow, and stool for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.\n\nEXCLUSION CRITERIA - Recipient\n\n1. Participants who are receiving any other investigational agents within 3 weeks prior to the beginning of conditioning.\n2. Active CNS involvement of primary hematologic malignancy\n3. Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers) which is metastatic, relapsed\u002Frefractory to treatment, or locally advanced and not amenable to intended curative treatment per standard of care.\n4. Prior checkpoint inhibitor therapy within 6 weeks prior to the beginning of conditioning.\n5. Prior history of seizure.\n6. Uncontrolled infection.\n7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents used in study.\n8. Positive beta-HCG serum or urine pregnancy test performed in females of childbearing potential at screening. (A low positive test in a post-menopausal woman may not be exclusionary if deemed not indicative of pregnancy per gynecology.)\n9. Uncontrolled intercurrent illness evaluated by medical history, physical exam, EKG, and laboratory testing (e.g., severe endocrinopathy, disseminated intravascular coagulation, profound electrolyte disturbance) that would make it unsafe to proceed with transplantation.\n\nEXCLUSION CRITERIA - donor\n\n1\\. Pregnancy","75 Years",{"count":395,"type":22},155,[62],"Background:\n\nHigh-risk blood cancers (leukemias and lymphomas) often come back after treatment, and many cannot be cured with chemotherapy alone. These cancers may be treated and potentially cured in 2 ways: (1) Bone marrow transplant (allogeneic hematopoietic cell transplantation, or alloHCT) gives immune and blood stem cells from a donor. These new cells can attack the cancer and also grow into healthy blood. (2) Chimeric antigen receptor (CAR) T-cell therapy takes immune cells and changes them in a lab to better recognize and target certain cancers. But these 2 treatments are not usually given at the same time.\n\nObjective:\n\nTo test alloHCT and CAR-T cell therapy, used together, in people with high-risk blood cancers.\n\nEligibility:\n\nPeople aged 18 to 75 years with an aggressive blood cancer that has a protein on the surface called CD19. A healthy related donor aged 12 years or older is also needed; this donor may be a parent or child or may be some siblings or even extended family members, but has to be half-matched at something called the HLA (human leukocyte antigen).\n\nDesign:\n\nParticipants will be screened. They will have imaging scans, blood tests, and tests of their heart and lung function. They will have eye and dental exams. They may have fluid drawn from around their spinal cord (spinal tap) and tissue taken from inside a bone (bone marrow biopsy).\n\nHealthy donors will provide bone marrow, immune cells, and about 9 tablespoons of blood for both the recipient s treatment and for research. They will also provide stool, saliva, and oral swabs just for research.\n\nRecipient participants will stay in the hospital for 4 to 6 weeks. They will be given drugs over 6 days to prepare for the cell therapies. Both the donor bone marrow cells and CAR-T-cells will be given through a tube inserted into a vein. They will receive drugs to reduce complications after the treatments.\n\nParticipants will remain within a 1-hour drive of the hospital for 2 to 3 months after they leave the hospital. They will have frequent visits during that time. They will continue to have periodic follow-up visits for 5 years.\n\n...",[399,253],"Hematologic Malignancies",[401,402,403,404],"Chimeric-Antigen-Receptor T-cell Therapy","High Risk Hematologic Malignancy","CD19","Hematopoietic Cell Transplant",{"date":42,"type":43},{"date":407,"type":43},"2025-11-14",{"date":409,"type":22},"2034-10-01",{"name":49,"class":50},{"id":412,"slug":413,"hasResults":12,"nctId":414,"briefTitle":415,"officialTitle":416,"acronym":4,"eligibilityCriteria":417,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":418,"targetDuration":4,"studyType":23,"phases":420,"briefSummary":422,"conditions":423,"keywords":424,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":428,"startDateStruct":429,"completionDateStruct":431,"leadSponsor":433,"locationsCount":51},"100598103","a-synthetic-lethality-focused-algorithm-to-identify-therapeutic-options-in-advanced-metastatic-breast-cancer-synthesis-breast-100598103","NCT07067138","A Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)","An Exploratory Study Using a Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)","-INCLUSION CRITERIA:\n\n1. Participants must have a histologically confirmed diagnosis of metastatic breast cancer. Note: Pathology testing outside NIH will be accepted for eligibility purposes.\n2. Participant tumor subtypes will be enrolled as follows:\n\n   * TNBC Cohort: TNBC will be defined as ER \\\u003C 10% or PR \\\u003C 10% by immunohistochemistry (IHC).\n   * Endocrine-Refractory Cohort: HR+ (ER+ and\u002For PR+) will be defined as ER \\>= 10% or PR \\>= 10% by IHC.\n   * For both cohorts, HER2 will be considered negative if not amplified as per ASCOCAP guidelines per IHC\u002FFISH. Note: HER2-low status will be regarded in accordance with NCCN guidelines (in which this designation serves as a predictive marker for trastuzumab deruxtecan, but participants are otherwise not considered eligible for other HER2-directed therapies).\n3. Participants must have been treated with at least one (1) line of systemic therapy after diagnosis of metastatic disease, anticipate or have progressive disease or adverse events requiring discontinuation of their current regimen, and must not be able to transition to another approved systemic therapy shown to improve overall survival.\n\n   -Participants with HR+ disease must be deemed refractory to endocrine therapy per their clinical team, with concordance by study team.\n\n   Note: Participants who cannot receive or decline to receive standard therapy that has been shown to prolong overall survival, or if such therapy is not deemed in the participant s best interest, will be eligible, if other eligibility criteria are met. If appropriate, participants may remain on treatment during biopsy, screening and initial tissue review\u002Ftesting for this study.\n4. Participants must have measurable disease per RECIST v1.1. Note: Palliative radiotherapy to site(s) of disease may be completed during screening as long as disease outside of the planned sites of radiation is available for response assessment.\n5. Archival tumor (preserved via FFPE) must be available from a biopsy performed within the past 6 months. The timeframe of 6 months is required to optimize reliability of ENLIGHT results. It is assumed that a participant has had no more than one (1) line of systemic treatment since the last biopsy. Participants who have had multiple intervening lines of therapy since biopsy was obtained will be reviewed by the study team to determine if another biopsy may be needed. Note: If archival tissue is not available within that timeframe, tissue from the next scheduled biopsy can be sent to NIH for testing. If it is not possible for a biopsy to be scheduled, the study team will evaluate the possibility of a biopsy being performed at the NIH for enrollment purposes.\n6. Age \\>=18 years.\n7. ECOG performance status \\\u003C2 (Karnofsky \\>60%)\n8. Participants must have organ and marrow function as defined below:\n\n   * Hemoglobin \\>= 8g\u002FdL\n   * Absolute neutrophil count \\>= 1,200\u002FmcL\n   * Platelets \\>=75,000\u002FmcL\n   * Total bilirubin \\\u003C= 1.5 x institutional upper limit of normal (In the case of known Gilbert's Disease, total bili \\>1.5 may be considered.)\n\n   (For participants with known liver involvement, \\\u003C=3x institutional upper limit of normal)\n\n   -AST(SGOT)\u002FALT(SGPT) \\\u003C= 3x institutional upper limit of normal\n\n   (For participants with known liver involvement, \\\u003C=5x institutional upper limit of normal)\n\n   -Creatinine \\\u003C 1.5 x normal institutional limits OR Creatinine clearance \\>=30 mL\u002Fmin\u002F1.73 m2\n9. Ability to take oral medications.\n10. Participants with an existing diagnosis of diabetes or hypertension, must have disease well-controlled with at least annual physician follow-up.\n11. Women of child-bearing potential and men with a partner of child-bearing potential must be willing to use appropriate contraception in the event that they match to a therapy that requires such. The duration of contraception use will depend on the therapy assigned.\n12. Willingness to comply with required study procedures and visits for the duration of study.\n13. Participants with asymptomatic brain metastases may be included if metastases have been previously treated with local therapy including radiation at least 4 weeks prior to first dose of treatment and there is no indication for additional local therapy (including active progression).\n14. Participants with human immunodeficiency virus (HIV) must be on an effective anti-retroviral therapy with undetectable viral load for at least the last 6 months.\n15. Participants with evidence of chronic hepatitis B virus (HBV) infection, must have HBV viral load that is undetectable on suppressive therapy, if indicated.\n16. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection must be currently on treatment, with undetectable HCV viral load.\n17. Participants with a prior or concurrent malignancy are eligible if the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the off-label therapies offered on this study in the opinion of the Principal Investigator (PI) and are otherwise eligible for this trial.\n18. Participants with current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Note: To be eligible for this trial, participants should be class 2B or better.\n19. Ability of participant to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA:\n\n1. Participants in active visceral crisis, symptomatic brain metastases requiring local therapy, or active leptomeningeal disease given the time required for testing and therapy selection.\n2. Participants with uncontrolled intercurrent illness evaluated by physical exam and chemistries or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant.\n3. Participants with the following active cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia (per medical record).\n4. Participants with lung disease requiring continuous oxygen supplementation.\n5. Participants with decompensated cirrhosis and\u002For end-stage kidney disease on dialysis.\n6. Participants with positive serum or urine beta-HCG pregnancy test performed at screening.\n7. Participants who are unable to provide tissue specimens of sufficient quality for use in this study. Quality of DNA and RNA is determined during screening. This may be due to issues with biopsy sample collection, inadequate RNA extraction, or quality control failure. Participants may be re-screened if initial specimens are not adequate, if they are amenable to re-biopsy, and additional site(s) of disease for adequate re-sampling are available.",{"count":419,"type":22},175,[421],"NA","Background:\n\nBreast cancer is the most common cancer in US women. There are different types of breast cancers; some are aggressive and difficult to treat. Researchers want to know if an algorithm (ENLIGHT) can help choose approved drugs that will treat these cancers more effectively.\n\nObjective:\n\nTo test whether ENLIGHT can find better treatments for aggressive breast cancers.\n\nEligibility:\n\nPeople aged 18 years and older with triple-negative or endocrine therapy resistant breast cancer; the cancer must have either failed to respond to treatment or come back after treatment.\n\nDesign:\n\nParticipants will be screened. A sample of tissue taken from the tumor will be tested using ENLIGHT as well as another method (TruSight Oncology 500).\n\nParticipants will be assigned to 1 of 3 groups based on the algorithm search results:\n\nGroup 1: No drug option was recommended. Participants will continue with their standard treatment with their local doctors.\n\nGroup 2: A drug already approved for the participant's disease was recommended, but the participant has not yet received it. These results will be sent to the participant's local doctors. Participants may return to the NIH if their disease gets worse after using the suggested drugs.\n\nGroup 3: A drug approved for other uses was recommended. Participants will be treated with the recommended drugs at the NIH; their care will be managed by an NIH doctor. They will continue to receive treatment as long as the drugs are helping them. They will have follow-up visits for 2 years after treatment ends.\n\nParticipants who are not treated at the NIH will be contacted for a check on their health every 3 months for 2 years.",[202,203,204,205],[425,207,426,427],"ENLIGHT","Her2","NSR device",{"date":42,"type":43},{"date":430,"type":43},"2026-02-23",{"date":432,"type":22},"2029-08-04",{"name":49,"class":50},{"id":435,"slug":436,"hasResults":12,"nctId":437,"briefTitle":438,"officialTitle":439,"acronym":4,"eligibilityCriteria":440,"healthyVolunteers":12,"sex":372,"minAge":18,"maxAge":4,"enrollmentInfo":441,"targetDuration":4,"studyType":23,"phases":443,"briefSummary":444,"conditions":445,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":454,"startDateStruct":455,"completionDateStruct":457,"leadSponsor":459,"locationsCount":460},"100597706","phase-3-induction-pembrolizumab-and-chemotherapy-followed-by-pembrolizumab-before-chemoradiation-and-pembrolizumab-maintenance-compared-to-standard-chemoradiation-with-pembrolizumab-followed-by-pembrolizumab-maintenance-in-high-risk-cervical-cancer-100597706","NCT07061977","Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer","NRG-GY037: A Phase III Study of Induction Pembrolizumab and Chemotherapy Followed by Chemoradiation and Pembrolizumab Versus Chemoradiation and Pembrolizumab Both Followed by Pembrolizumab for High Risk Locally Advanced Cervical Cancer","Inclusion Criteria:\n\n* Patients must have pathologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma\n* Patients must have locally advanced cervical cancer (LACC) with T3 or T4 disease with or without lymph node involvement:\n\n  * IIIA (T3aN0M0)\n  * IIIB (T3bN0M0)\n  * IIIC1(T3aN1M0, T3bN1M0)\n  * IIIC2 (T3aN2M0, T3bN2M0)\n  * IVA (T4aN0M0, T4aN1M0, T4aN2M0) No prior hysterectomy defined as removal of the entire uterus.\n  * NOTE: prior partial\u002Fsubtotal hysterectomy for reasons other than cervical cancer are eligible to participate in the study. No plan to perform a hysterectomy as part of initial cervical cancer therapy.\n\nNo paraaortic lymph node (PALN) metastases above the T12\u002FL1 interspace.\n\n* Note: Nodal status can be confirmed by imaging (CT, MRI, or PET\u002FCT), fine needle aspirate\u002Fcore biopsy, extra peritoneal biopsy, laparoscopic biopsy, or lymphadenectomy.\n\nRadiologic definition of lymph node staging:\n\n* N1:\n\n  * One or more pelvic lymph nodes with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and\u002For\n  * One or more pelvic lymph nodes with short axis diameter of ≥ 10 mm and standardized uptake value maximum (SUVmax) ≥ 2.5 by fludeoxyglucose (FDG)-PET\n* N2:\n\n  * One or more para-aortic lymph node with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and\u002For\n  * One or more para-aortic lymph node with short axis diameter of ≥ 10 mm and SUVmax ≥ 2.5 by FDG-PET\n\n    * No prior definitive surgical, radiation, or systemic therapy for cervical cancer\n    * No prior immunotherapy\n    * No prior pelvic radiation therapy for any disease\n    * Age ≥ 18\n    * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2\n    * Not pregnant and not nursing\n    * Absolute neutrophil count (ANC) ≥ 1,500 cells\u002Fmm\\^3\n    * Platelets ≥ 100,000 cells\u002Fmm\\^3\n    * Hemoglobin ≥ 8 g\u002Fdl (Note: The use of transfusion or other intervention to achieve hemoglobulin \\[Hgb\\] ≥ 8 g\u002Fdl is acceptable)\n    * Creatinine clearance (CrCL) of ≥ 50 mL\u002Fmin by the Cockcroft-Gault formula\n    * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)\n    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN\n    * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better\n    * No active infection requiring parenteral antibiotics\n    * No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacille Calmette Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed\n    * No diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior registration\n    * No active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed\n    * No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis\n    * No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)",{"count":442,"type":22},336,[329],"This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.",[446,447,448,449,450,451,452,453],"Locally Advanced Cervical Adenocarcinoma","Locally Advanced Cervical Adenosquamous Carcinoma","Locally Advanced Cervical Squamous Cell Carcinoma","Stage IIIA Cervical Cancer FIGO 2018","Stage IIIB Cervical Cancer FIGO 2018","Stage IIIC1 Cervical Cancer FIGO 2018","Stage IIIC2 Cervical Cancer FIGO 2018","Stage IVA Cervical Cancer FIGO 2018",{"date":42,"type":43},{"date":456,"type":43},"2025-11-05",{"date":458,"type":22},"2030-12-31",{"name":49,"class":50},315,{"id":462,"slug":463,"hasResults":12,"nctId":464,"briefTitle":465,"officialTitle":466,"acronym":4,"eligibilityCriteria":467,"healthyVolunteers":12,"sex":17,"minAge":468,"maxAge":469,"enrollmentInfo":470,"targetDuration":4,"studyType":199,"phases":4,"briefSummary":472,"conditions":473,"keywords":484,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":490,"startDateStruct":491,"completionDateStruct":492,"leadSponsor":494,"locationsCount":51},"100593350","clinical-genetics-branch-eligibility-screening-survey-100593350","NCT07005297","Clinical Genetics Branch Eligibility Screening Survey","Clinical Genetics Branch (CGB) Eligibility Screening Survey","* INCLUSION CRITERIA\n\nThere is no age restriction; therefore, viable neonates may be included. This eligibility screening protocol is intended for individuals meeting one or more of the following criteria:\n\n1. Personal or family history of a diagnosis of a syndrome being actively investigated in one of the following CGB study protocol:\n\n   * Protocol 000678: Medical history of neoplasia of an unusual type, pattern, or number.\n   * Protocol 11C0255: A personal history of adrenal cortical carcinoma or choroid plexus carcinoma at any age, regardless of family history, or family or personal medical history of neoplasia consistent with the diagnosis of LFS or LFL.\n   * Protocol 20C0107: Individuals with a clinical diagnosis of a RASopathy, including Costello syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines, Cardiofaciocutaneous syndrome, Legius syndrome, capillary arteriovenous malformation syndrome, or others, are eligible. Published clinical diagnostic criteria exist for most of the clinical RASopathy syndromes and differ by syndrome. It will be uncommon for individuals to have a clinical diagnosis and not have had molecular genetic testing. All individuals considered by the study team to be at risk for a RASopathy who have not had prior genetic testing will have this completed as part of the study. The rare individuals with a clinical diagnosis of a RASopathy who are not found to carry a corresponding pathogenic or likely pathogenic variant in a known RASopathy gene will be considered for exome analysis for identification of potentially novel RASopathy germline variation.\n   * Protocol 11C0034: An individual with histologically-confirmed PPB and\u002For other DICER1-related tumors\n   * Protocol 02C0052: The participants will be affected by an IBMFS, or be members of a family with an IBMFS, and be at risk of being affected or carriers of the syndrome. Except for the rare X-linked recessive disorder (e.g. some dyskeratosis congenita patients), there should be equal numbers of male and female probands and family members. These IBMFS have been reported in most racial and ethnic groups, and thus all such groups will be included. The age range will be from birth to old age (grandparents of probands). The majority of the probands will be children (10-20% will be adults), and their parents and grandparents will be adults. All racial\u002Fethnic groups are eligible.\n   * Protocol 02C0211: Personal medical history of melanoma of an unusual type, pattern, or number diagnosed at any age.\n   * Protocol 78C0039: Family or personal medical history of neoplasia of an unusual type, pattern, or number\n2. Personal or family history of medical condition, malignancy, and\u002For benign neoplasm suggestive of hereditary cancer predisposition being actively investigated in the following CGB study protocol:\n\n   * Protocol 000678: Known or suspected factor(s) predisposing to neoplasia, either genetic and\u002For congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.)\n   * Protocol 11C0255: An individual with a sarcoma diagnosed under the age of 45; AND - At least one first-degree relative (parents, brothers, sisters and children) with a cancer of any kind diagnosed under the age of 45; AND - A third family member who is either a first- or second-degree relative (such as grandparents, aunts, uncles, nieces, nephews, and grandchildren) with cancer diagnosed under the age of 45 or having a sarcoma at any age.\n   * Protocol 001109: On referral, persons \\>= 12 years with Fanconi Anemia (FA) primarily from North America will be included. An individual with FA who is 8 -11 years can also be included if they have a history of persistent oral potentially malignant lesion (OPMLs), dysphagia, or other concerning symptoms. Individuals with prior cancer diagnosis are eligible.\n   * Protocol 11C0034: An individual from the general population with one or more of the unique tumors of the types associated with DICER1 including (but not exclusively), PPB, cystic nephroma, ovarian Sertoli-Leydig cell and other sex cordstromal tumors, ocular medulloepithelioma, nasal chondromesenchymal hamartoma, Wilms tumor, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, ovarian sarcoma, CNS sarcoma and\u002For thyroid cancer - regardless of their family history. Additional DICER1-related neoplasms may be identified in the future, and they will be added to the protocol as needed\n   * Protocol 02C0052: Fanconi anemia: FA patients have relatively specific birth defects, aplastic anemia, increased chromosome breakage in cells cultured with a DNA crosslinking agent such as mitomycin C (MMC) or diepoxybutane (DEB), pathogenic variant(s) in one of the cloned genes (six genes at this time), or assignment to one of the 7 or more complementation groups. Bone marrow failure is NOT required for the diagnosis, and approximately 25% do not have birth defects. FA has been diagnosed from birth to \\>50 years of age. FA Proven = positive chromosome breakage result, and\u002For pathogenic variant(s) in a known FANC gene. Patients in whom FA is suspected but whose chromosome breakage test is negative will still be considered if they have sufficient findings that lead the Principal Investigator to think they may be somatic mosaics and warrant further evaluation. Diamond Blackfan anemia: DBA patients have pure red cell aplasia with reticulocytopenia. Approximately 30% have physical abnormalities, often involving malformations of the thumbs. Approximately 90% are diagnosed within the first year of life. A pathogenic variant in a known DBA gene (RPS19 is currently the only known gene) is diagnostic, but lack of a pathogenic variant does not rule out DBA, since the cloned gene is responsible for only approximately 25% of the disease. Since many cases are sporadic or occur in families with silent carriers, patients without a positive family history will be included. Currently DBA is diagnosed by clinical findings after exclusion of known causes of red cell aplasia. Approximately 90% have elevated red cell adenosine deaminase levels, a finding which is supportive, but not diagnostic, of DBA. Dyskeratosis congenita: DC patients develop dyskeratotic nails, lacy hyperpigmentation of the skin and mucous membrane leukoplakia as they age (the diagnostic clinical triad; two of the three are required for a firm diagnosis). Findings in young patients may be very subtle, and diagnoses are usually made in teenagers or young adults. More than 75% are male. DC patients are often diagnosed without hematologic abnormalities by dermatologists; however, some patients present with aplastic anemia prior to the evolution of the syndrome-related physical features. A pathogenic variant in the DKC1 gene is diagnostic, but normal DKC1 does not exclude DC. The diagnosis is often clinical, after exclusion of FA and other IBMFS. Shwachman Diamond Syndrome: SDS patients have neutropenia, malabsorption and failure to thrive due to exocrine pancreatic insufficiency. The gene has not yet been cloned. Pancreatic insufficiency is documented by direct measurement of pancreatic enzymes, low serum immunoreactive trypsinogen, or elevated fecal fat levels. Neutropenia requires an absolute neutrophil count of \\\u003C1500\u002Fmm3 on multiple occasions. Other causes of malabsorption such as cystic fibrosis, Pearson syndrome, and Johansson-Blizzard syndrome must be excluded. Cystic fibrosis will be excluded in patients who have a positive sweat test performed at an approved CF center. Amegakaryocytic thrombocytopenia: These patients have early onset thrombocytopenia (\\\u003C150,000\u002Fmm3), usually within the first year of life, due to absent, diminished, or abnormal bone marrow megakaryocytes, without antiplatelet antibodies. Physical examination is often normal; in particular, there are no abnormalities of the radial rays. Pathogenic variant(s) in the MPL gene are diagnostic, but normal MPL does not exclude this diagnosis. Thrombocytopenia absent radii: TAR patients have absent radii, usually bilateral, with intact thumbs (in contrast with FA and trisomy 18, where thumbs are absent if radii are absent), and thrombocytopenia at birth. Other radial aplasia syndromes such as Holt-Oram syndrome or VATER syndrome must be excluded. Severe Congenital Neutropenia: Patients with SCN have persistent and noncyclic low absolute neutrophil counts, with more than 2 measurements \\\u003C200\u002Fmm3, and a history of pyogenic infections during the first year of life, and bone marrow maturation arrest at the promyelocyte\u002Fmyelocyte stage. They do not have birth defects, and they usually have normal hemoglobin and platelet counts. They are designated Kostmann Syndrome (KS) only if there is a pattern of autosomal recessive inheritance. Pathogenic variant(s) in the neutrophil elastase gene (ELA2) are supportive of the diagnosis of SCN, but do not distinguish SCN patients from those with cyclic neutropenia, which is milder and not preleukemic. Many of the cases of SCN have been shown to be due to dominant pathogenic variant(s)s in ELA2. Pearson Syndrome: Pearson syndrome consists of malabsorption, neutropenia, alone or with anemia and\u002For thrombocytopenia, and metabolic acidosis. Onset is in infancy or early childhood. The diagnosis is strongly suspected if bone marrow examination reveals vacuoles in myeloid and erythroid progenitors, and ring sideroblasts. Confirmation derives from detection of deletions in mitochondrial DNA, which range from 2 to 8 kb in size, and include the respiratory enzymes. Absence of reports to date of cancer or leukemia in this syndrome may derive from early death due to the metabolic problems. Other bone marrow failure syndromes: There are occasional patients with a pattern of hematologic abnormalities, physical findings, malignancies, or family histories which are not characteristic of the syndromes described above, but which nonetheless suggests that they have a genetic bone marrow failure syndrome. There may be similar cases in the literature, or in the experience of the investigator, which may ultimately lead to assignment of these patients to a known or new syndrome. There are additional bone marrow failure syndromes which are even more rare, such as Revesz, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia, etc. Syndromic classification of extremely rare disorders is facilitated if they are collected in one center. Since malignancy is often part of these syndromes, they will be eligible for enrollment in this protocol.\n   * Protocol 02C0211: Known or suspected factor(s) predisposing to melanoma, either genetic or congenital factors (giant congenital nevi, dysplastic nevi, Spitzoid tumors), or unusual demographic features (e.g., very young age of onset, multiple melanomas, previous history of heritable retinoblastoma, Hodgkin's disease, lymphoma, immunodeficiency syndrome, or organ transplant).\n   * Protocol 10CN188: Diagnose with chordoma or related tumor at any age and any primary site.\n   * Protocol 78C0039: Known or suspected factor(s) predisposing to neoplasia, either genetic and\u002For congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.). Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are required. The types of familial tumors that we are currently actively accruing include Familial Cancers: bladder, brain, chordoma, lung, nevoid basal cell carcinoma syndrome (NBCC) Familial Benign Neoplasms: meningiomas, neurofibromatosis 2 (bilateral acoustic neurofibromatosis) The types of familial tumors under active accrual and study are predominantly investigator- and hypothesis-driven. This approach permits CGB investigators to remain alert to the opportunities afforded by clusters of rare tumors in families and individuals, and to be more responsive to the dynamic research priorities in cancer genetics.\n3. Personal or family history of a genetic variant in a hereditary cancer predisposition being actively investigated in the following CGB study protocols:\n\n   * Protocol 11C0255: A personal history of a germline TP53 mutation; or, - A first or second- degree relative of a TP53 mutation carrier, regardless of mutation status\n   * Protocol 20C0107: Individuals with a germline variant (P\u002FLP or a variant of uncertain significance but predicted bioinformatically to be damaging) in a RASopathy-associated gene are eligible. These include but are not limited to: BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, MAP3K8, MRAS, NRAS, PPP1CB, PTPN11, RAF1, RASA1, RASA2, RIT1, RRAS, SHOC2, SOS1, SPRED1. From herein, we refer to 1) individuals with germline pathogenic variation in a RAS pathway gene AND 2) individuals with a clinical RASopathy diagnosis but in whom a genetic variant has not yet been identified as \"carriers.\" The first member of a family to be identified is termed a \"proband.\"\n   * Protocol 11C0034: An individual with a known or suspected DICER1 disease associated variant.\n   * Protocol 02C0052: An individual with a pathogenic variant(s) in a known FANC gene. Individual with Diamond Blackfan Anemia with a pathogenic variant in a known DBA gene (RPS19). Individuals with Dyskeratosis congenita with a pathogenic variant in the DKC1 gene. Individuals with Amegakaryocytic thrombocytopenia with pathogenic variants) in the MPL gene. Individuals with Severe Congenital Neutropenia with a pathogenic variant(s) in the neutrophil elastase gene (ELA2).\n\nEXCLUSION CRITERIA\n\nWhile this protocol is intended to be used by those meeting the inclusion criteria above, there are no explicit exclusion criteria for this study, since the initiative to complete the eligibility screener survey is at the will of the participant or his or her parent\u002Fguardian\u002FLAR.","1 Year","99 Years",{"count":471,"type":22},1000,"Background:\n\nClinical Genetics Branch (CGB) researchers study individuals and populations at high genetic risk of cancer in order to improve our understanding of cancer and to improve cancer care. There are currently 6 open clinical genetics studies at the CGB eligible for this screening process.\n\n* 02C0052: Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study (Cancer in Bone Marrow Failure)\n* 11C0255: Clinical, Epidemiologic, and Genetic Studies of Li-Fraumeni Syndrome (Li Fraumeni Syndrome Study)\n* 11C0034: DICER1-Related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study (Pleuropulmonary Blastoma)\n* 02C0211: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma (Melanoma-Prone Families)\n* 10CN188: Genetic Clues to Chordoma Etiology: A Protocol to Identify Sporadic Chordoma Patients for Studies of Cancer-susceptibility Genes (Sporadic Chordoma Study)\n\nThe following studies have their own study-specific screeners. If you are interested in these studies, please click the links below to fill out the relevant study screener:\n\n* 001109: Defining the Natural History of Squamous Cell Carcinoma in Fanconi anemia (SCC Screening in FA): https:\u002F\u002Fservice.cancer.gov\u002Ffanconi\n* 20C0107: Clinical, Genetic, and Epidemiologic Study of Children and Adults with RASopathies (RASopathies Study): https:\u002F\u002Fservice.cancer.gov\u002Fmyras\n\nObjective:\n\nTo find people to participate in active CGB cancer research studies.\n\nEligibility:\n\nPeople of any age who meet the eligibility criteria for one of the open CGB cancer research studies. You can learn more about the CGB cancer research studies by clicking on the links to the study-specific websites above. This typically involves a personal or family history of certain cancers that are being studied by researchers at CGB.\n\nDesign:\n\nParticipants will fill out a screening questionnaire to determine if they are eligible to participate in one or more CGB clinical genetics studies. The survey asks about personal health history, including cancer; family history; and genetic testing results and takes 15 to 20 minutes.\n\nEach study has its own eligibility criteria. Survey respondents will select which study (or studies) that are interested in participating in, and the relevant study team(s) will review the screener to determine eligibility to participate in the study. Participants who are determined to be eligible for a study based on their screener will be contacted by the respective study team to learn more about the study and to consent to enroll in the study if they choose to do so. Participants who consent to enroll in a study may be asked to provide medical records; samples such as blood, saliva, or other tissues; and to participate in activities such as phone interviews or surveys. They may be invited for evaluations at the clinical center. Every study activity is voluntary. None of the studies provide treatments. Participants may be contacted to consider enrolling in future studies.",[474,475,476,477,478,479,480,481,482,483],"Melanoma","Li-Fraumeni Syndrome","Pulmonary Blastoma","Chordoma","Congenital Bone Marrow Failure Syndromes","Costello Syndrome","Fanconi Anemia","CFC Syndrome (CFCS)","Legius Syndrome","RASopathies",[480,475,485,486,477,487,483,488,489],"Clinical Genetics Branch, NCI","Hereditary Melanoma","DICER-1 syndrome","Cancer","Inherited Bone Marrow Failure Syndromes",{"date":42,"type":43},{"date":45,"type":22},{"date":493,"type":22},"2036-01-01",{"name":49,"class":50},{"id":496,"slug":497,"hasResults":12,"nctId":498,"briefTitle":499,"officialTitle":500,"acronym":4,"eligibilityCriteria":501,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":502,"enrollmentInfo":503,"targetDuration":4,"studyType":23,"phases":505,"briefSummary":506,"conditions":507,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":509,"startDateStruct":510,"completionDateStruct":512,"leadSponsor":514,"locationsCount":274},"100586633","phase-2-testing-the-addition-of-venetoclax-or-gemtuzumab-ozogamicin-go-to-usual-treatment-regimen-cytarabine-and-daunorubicin-73-for-core-binding-factor-acute-myeloid-leukemia-cbf-aml-to-improve-response-a-myelomatch-treatment-trial-100586633","NCT06917911","Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, \"7+3\") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)","Phase II Study of Cytarabine + Daunorubicin (7 + 3) + Gemtuzumab Ozogamicin vs. Cytarabine + Daunorubicin (7 + 3) + Venetoclax for the Treatment of Newly Diagnosed Core Binding Factor Acute Myeloid Leukemia (CBF-AML) in Younger Adults: A MyeloMATCH Substudy","Inclusion Criteria:\n\n* GENERAL MYELOMATCH CRITERIA: Patients must be registered to the Master Screening and Reassessment Protocol, MYELOMATCH, and assigned to this protocol by the MATCHBox Treatment Verification Team\n* GENERAL MYELOMATCH CRITERIA: Participants must not have received prior anti-cancer therapy for AML or myelodysplastic syndrome (MDS)\n\n  * Note: Hydroxyurea to control the white blood cell count (WBC) and cytarabine up to 1g for urgent cytoreduction is allowed.\n  * Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility\n* GENERAL MYELOMATCH CRITERIA: Participants must not receive any cytarabine-containing therapy other than up to 1g of cytarabine, which is allowed for urgent cytoreduction. Hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed\n* Diagnosis of AML with t(8;21)(q22;q22.1)\u002FRUNX1::RUNX1T1 or AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)\u002FCBFB::MYH11. No FLT3 mutation (these patients should be considered for a FLT3-focused MYELOMATCH study)\n* Secondary CBF-AML (e.g., prior pre-leukemic hematologic malignancy or history of chemotherapy\u002Fradiation therapy) is allowed.\n* No prior AML or MDS-directed therapy except for urgent treatment of leukocytosis with leukapheresis, cytarabine, and hydroxyurea, Prior intrathecal chemotherapy for central nervous system (CNS) involvement of AML is permitted\n* Age 18-59 years\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3\n* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless patient has a history of Gilbert syndrome and direct bilirubin is ≤ 1.5 x ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x upper limit of normal (ULN)\n* Glomerular filtration rate (GFR) ≥ 30 mL\u002Fmin\u002F1.73m\\^2\n* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Participants with CNS disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease\n* Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* No known medical condition causing an inability to swallow oral formulations of agents","59 Years",{"count":504,"type":22},162,[25],"This phase II MYELOMATCH treatment trial compares the effect of venetoclax to gemtuzumab ozogamicin, when given with cytarabine and daunorubicin (\"7+3\" regimen), for the treatment of patients with core binding factor acute myeloid leukemia (CBF-AML). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to an antitumor antibiotic drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers ozogamicin to kill them. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with cytarabine and daunorubicin may have fewer side effects and be as effective or better than the combination with gemtuzumab ozogamicin in treating patients with core binding factor AML.",[508],"Core Binding Factor Acute Myeloid Leukemia",{"date":42,"type":43},{"date":511,"type":22},"2027-02-02",{"date":513,"type":22},"2027-11-25",{"name":49,"class":50},{"id":516,"slug":517,"hasResults":12,"nctId":518,"briefTitle":519,"officialTitle":520,"acronym":4,"eligibilityCriteria":521,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":522,"targetDuration":4,"studyType":23,"phases":524,"briefSummary":525,"conditions":526,"keywords":538,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":548,"startDateStruct":549,"completionDateStruct":550,"leadSponsor":552,"locationsCount":51},"100585569","autologous-t-cells-transduced-with-retroviral-vectors-expressing-tcrs-for-participant-specific-neoantigens-in-patients-with-hematologic-malignancies-100585569","NCT06904066","Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies","A Phase I Study of Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Other Hematologic Malignancies","* INCLUSION CRITERIA:\n\nMalignancy diagnosis requirements:\n\n-Eligible diagnoses include AML (acute myeloid leukemia), MDS (myelodysplastic syndrome), CMML(chronic myelomonocytic leukemia), CML (chronic myeloid leukemia), and T-ALL (T-acute lymphoblastic leukemia\u002Flymphoma) meeting standard diagnostic criteria as described in the 5th edition World Health Organization Classification of Hematologic Tumors and\u002For the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Multiple myeloma participants meeting International Working Group diagnostic criteria are eligible. These diagnostic criteria can be met at any time during the course of the participant s malignancy. Atypical CML is not an eligible diagnosis.\n\nNOTE: Pathology reports are acceptable to confirm eligibility.\n\nMalignancy mutation and HLA requirements:\n\n* Detection of at least one of the neoepitope-forming TP53 or RAS mutations that are listed in Table 3 in on the TruSight Oncology (TSO) 500 sequencing panel (NSR device) performed in the NCI Laboratory of Pathology is required. RAS mutations can be in NRAS, KRAS or HRAS as these oncogenes have the same amino acid sequence at the location of the targeted neoepitopes. A variant allele frequency (VAF) of at least 5% is required for a mutation to be eligible. This criterion can be met at any time within 60 days prior to apheresis regardless of treatment history during this 60-day period. DNA for sequencing comes from bone marrow.\n* Presence of the correct HLA type needed to present one of the targeted neoepitopes as shown in Table 3. HLA typing data from any time-point prior to apheresis can be used to meet this requirement.\n\nTable 3: Eligibility requirements for the targeted mutation and HLA type\n\nTargeted mutation - TP53 R175H; HLA Type - A\\*02:01\n\nTargeted mutation - TP53 Y220C; HLA Type - A\\*02:01\n\nTargeted mutation - TP53 R248W; HLA Type - A\\*68:01\n\nTargeted mutation - Ras G12V; HLA Type - A\\*11:01\n\nTargeted mutation - Ras G12D; HLA Type - A\\*11:01\n\nTargeted mutation - Ras G12D; HLA Type - C\\*08:02\n\nTargeted mutation - Ras G12V; HLA Type - C\\*01:02\n\nMalignancy burden requirements:\n\n* For AML and MDS, bone marrow myeloblast percentage must be \\>=5% of nucleated cells in either bone marrow aspirate or biopsy. Myeloblasts can be defined by immunohistochemistry or by cytochemistry stains including but not limited to myeloperoxidase.\n* For T-ALL, bone marrow T-cell blast percentage must be \\>=5% of nucleated cells in either bone marrow aspirate or biopsy. T cells can be defined by cytochemistry or immunohistochemistry or flow cytometry.\n* For multiple myeloma, plasma cells having a phenotype consistent with multiple myeloma must be detected at any frequency by multiparameter bone marrow flow cytometry or total plasma cells must be at least 6% on bone marrow core biopsy or bone marrow aspirate.\n* For CMML, bone marrow blast (including monocytic blast equivalent) percentage must be \\>=6% of bone marrow nucleated cells by cytochemistry or immunohistochemistry of bone marrow aspirate or biopsy.\n* For CML measurable leukemia is defined as molecular detection of BCR-ABL1 at a ratio of \\>1.0% to ABL1 or another housekeeping gene on The International Scale (IS) in either blood or bone marrow.\n\nMalignancy prior treatment and risk category criteria\n\n\\- Participants with AML, MDS, CML, CMML, and T-ALL who have not had prior allogeneic hematopoietic stem cell transplantation (alloHSCT) must be unwilling or unable to undergo alloHSCT.\n\nNOTE: Unable to undergo alloHSCT could be due to lack of access to transplantation or not meeting transplant eligibility criteria at one or more transplant centers where the participant was evaluated by a transplant physician.\n\n* Participants with primary, secondary, or treatment-related AML that did not go into remission after induction therapy are eligible regardless of history of alloHSCT.\n* Myelodysplastic syndrome (MDS)\n\n  * Participants with MDS must have had high or very high risk MDS as determined by IPSS-R or IPSS-M (https:\u002F\u002Fmds-risk-model.com) at any time point.\n  * Participants with MDS must have received previous treatment with at least one of the following: a hypomethylating agent, cytotoxic chemotherapy, or alloHSCT. Participants with primary or treatment-related MDS are eligible.\n  * Participants with MDS\u002FAML with mutated TP53 are eligible.\n* Participants with CMML must have had a CMML-specific prognostic scoring system-Molecular (CPSS-Mol) score of \\>=2 (Intermediate-2 or High risk groups) at any time-point and must have received at least one line of previous systemic treatment, which could have been alloHSCT.\n* Chronic myeloid leukemia (CML)\n\n  * Participants with chronic phase CML and a history of inadequate response to or intolerance of 3 or more tyrosine kinase inhibitors (TKIs) are eligible.\n  * In addition, participants who have received at least one of bosutinib, dasatinib, or nilotinib in addition to either ponatinib or asciminib are eligible. Participants in accelerated phase or blast crisis are eligible if they have received at least one TKI.\n  * Participants who have received a prior HSCT are eligible provided they have also received at least 2 TKIs and meet other eligibility criteria.\n* Participants with T-ALL must have T-ALL that did not go into CR with induction therapy or that relapsed.\n* Participants with relapsed AML who are unable to undergo alloHSCT and meet other eligibility requirements are eligible.\n* Multiple Myeloma\n\n  * Participants with multiple myeloma must have received at least 3 different prior systemic treatment regimens for multiple myeloma. Participants must have prior exposure to an imid such as lenalidomide, a proteosome inhibitor, and a BCMA-targeting CAR T-cell therapy, such as monoclonal antibody, or bispecific antibody.\n  * Multiple myeloma participants with a history of alloHSCT are eligible\n  * Participants with multiple myeloma must also have measurable multiple myeloma\n\ndefined by at least one of the criteria below:\n\n* Serum M-protein greater or equal to 1.0 g\u002FdL.\n* Urine M-protein greater or equal to 200 mg\u002F24 h.\n* Serum free light chain (FLC) assay: involved FLC level greater or equal to 10mg\u002FdL (100 mg\u002FL) provided serum FLC ratio is abnormal.\n* A biopsy-proven plasmacytoma at least 2.0 cm in largest dimension.\n* Bone marrow core biopsy with 30% or more plasma cells.\n\nOther inclusion criteria\n\n* Blast cells \\\u003C=1% of white blood cells as measured by CBC and differential before apheresis\n* Plasma cells \\\u003C=1% of white blood cells as measured by CBC and differential before apheresis\n* Participants must be willing to undergo intensive care unit care including mechanical ventilation if necessary\n* Participants must not have received systemic chemotherapy for at least 14 days prior to start of lymphodepleting chemotherapy or apheresis, and chemotherapy-related toxicities other than cytopenias must have recovered to grade 0 or grade 1 by the time of apheresis. The one exception is if necessary to control AML, CML, or CMML, hydroxyurea can be administered up to 7 days prior to apheresis.\n* Participants who have received alloHSCT must have received a transplant from either a fully matched sibling or 10\u002F10 HLA-matched unrelated donor.\n* Recipients of alloHSCT must be at least 100 days post-transplant before the apheresis.\n* Subjects must be willing to be co-enrolled on NCI protocol 03C0277 and 09C0161.\n* Age must be \\>=18 and \\\u003C= 75 years old\n* Clinical performance status of ECOG 0 or 1\n* Participants must have adequate organ function as defined below:\n\n  * Hemoglobin: \\>=8 g\u002FdL without red blood cell transfusions for 7 days prior to blood count check\n  * Platelets: \\>=45,000\u002FmcL without transfusion support in the 7 days prior to the blood count check\n  * Absolute neutrophil count: \\>=850\u002FmcL without exogenous growth factor administration within the 10 days prior to the blood count check\n  * Total bilirubin: \\\u003C= 2.0 mg\u002FdL. Except for participants with Gilbert s syndrome (who must have a total bilirubin \\\u003C3 mg\u002FdL)\n  * Alanine transaminase (ALT) and aspartate transaminase (AST): \\\u003C= to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. If liver involvement with malignancy is detected, ALT and AST must be \\\u003C= 5 times the upper limit of normal\n  * Serum Creatinine: \\\u003C= 1.5 mg\u002FdL\n* Participants who have received prior genetically-engineered T-cell therapies are eligible if at least 180 days have elapsed between the date of previous T-cell infusion and apheresis.\n* Room air oxygen saturation must be 93% or greater\n* Women of child-bearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \\[IUD\\], abstinence, surgical sterilization) starting at the time of study entry, for the duration of study therapy, and 12 months after the last dose of combined chemotherapy. NOTE: IOCBP is defined as any person who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.\n\nMen able to father children must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and for 4 months after the last dose of combined chemotherapy. We also will recommend these Men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, intrauterine device \\[IUD\\], surgical sterilization). Men able to father a child must not freeze or donate sperm within the same period.\n\n* Nursing participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of the study drug(s).\n* Hepatitis B surface antigen and hepatitis B core antibody tests must be negative. If either of these tests are positive, participants must have a negative blood PCR test for hepatitis B to enroll on the study.\n* Hepatitis C antibody test must be negative. If this test is positive, participants must have a negative blood PCR test for hepatitis C RNA to enroll on the study.\n* Cardiac ejection fraction of greater than or equal to 50% by echocardiography with no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 30 days prior to apheresis.\n* All participants must be willing to undergo mandatory bone marrow biopsy\u002F aspirates during the study.\n* Participants with a history of cigarette smoking of \\>5 pack years, a history of pulmonary disease, a history of alloHSCT, or chronic pulmonary symptoms must undergo pulmonary function testing and have an FEV1 \\>50% predicted and diffusing capacity for carbon monoxide \\>= 60%.\n* Subjects who received a previous allogeneic HSCT must have no (grade 0) acute GVHD and no chronic GVHD or mild chronic GVHD as defined.\n\n  --NOTE: Subjects with GVHD meeting the above criteria with local therapy (topical cutaneous steroids, inhaled steroids, and eye drops) will be eligible.\n* Potential participants must agree to stay within 1-hour drive of NIH clinical center from date of initial discharge until at least 14 days have elapsed since T cell infusion through the 14 day time period.\n* Ability of the participant to understand and the willingness to sign a written informed consent document.\n* Willing to sign a durable power of attorney.\n\nEXCLUSION CRITERIA:\n\n-For alloHSCT recipients only, subjects receiving any systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg\u002Fday prednisone or equivalent within 28 days prior to apheresis.\n\nNOTE: Topical corticosteroid preparations applied to the skin such as solutions, creams, and ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye drops are allowed.\n\n* Corticosteroids given for any indication at doses greater than 5 mg\u002Fday of prednisone or equivalent within 14 days before either apheresis or start of protocol chemotherapy.\n* Participants with MDS\u002FMyeloproliferative neoplasia overlap syndromes are not eligible.\n* Participants with acute promyelocytic leukemia are not eligible.\n* Participants who received a mis-matched sibling or haploidentical transplant are not eligible.\n* Tumor masses \\>=10 cm in largest diameter\n* Positive beta Human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP performed at screening.\n* Human T-cell lymphotropic virus type 1\u002F 2 (HTLV-1\u002FII) positive\n* HIV infection, as measured by seropositivity for HIV antibody.\n* Participants that require urgent therapy due to tumor mass effects on vital organ or tumor lysis syndrome.\n* Any significant illness that, in the opinion of the principal investigator, may impair the participant s tolerance of the study treatment as evaluated by medical history, physical exam, assess for hepatosplenomegaly, and chemistry laboratory evaluations.\n* Participants with a history of a previous malignancy are ineligible if the malignancy has not been in complete remission for at least 2 years or if the previous malignancy required treatment with surgery, radiation, or chemotherapy, including maintenance hormonal therapy, in the past 2 years. Exceptions to this requirement are participants who have had successful resection of the following types of skin cancer: nonmetastatic basal cell carcinoma or squamous cell carcinoma or stage 0 melanoma.\n* Suspected or confirmed active uncontrolled infections defined as fevers of \\>38 degrees within the past 24 hours without a known non-infectious source or participants requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours.\n* Acti...",{"count":523,"type":22},86,[62],"Background:\n\nBlood cancers (such as leukemias) can be hard to treat, especially if they have mutations in the TP53 or RAS genes. These mutations can cause the cancer cells to create substances called neoepitopes. Researchers want to test a method of treating blood cancers by altering a person s T cells (a type of immune cell) to target neoepitopes.\n\nObjective:\n\nTo test the use of neoepitope-specific T cells in people with blood cancers\n\nEligibility:\n\nPeople aged 18 to 75 years with any of 9 blood cancers.\n\nDesign:\n\nParticipants will have a bone marrow biopsy: A sample of soft tissue will be removed from inside a pelvic bone. This is needed to confirm their diagnosis and the TP53 and RAS mutations in their cancer cells. They will also have a skin biopsy to look for these mutations in other tissue.\n\nParticipants will undergo apheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein.\n\nThe T cells will be grown to become neoepitope-specific T cells.\n\nParticipants receive drugs for 3 days to prepare their body for the treatment. The modified T cells will be given through a tube inserted into a vein. Participants will need to remain in the clinic at least 7 days after treatment.\n\nParticipants will have 8 follow-up visits in the first year after treatment. They will have 6 more visits over the next 4 years. Long-term follow-up will go on for 10 more years.",[527,528,529,530,531,532,533,534,535,536,537],"Malignancy, Hematologic","Neoplasms, Hematologic","Neoplasms, Hematopoietic","Blood Cancer","Hematological Neoplasms","Hematopoietic Malignancies","Dysmyelopoietic Syndromes","Hematopoetic Myelodysplasia","Myeloid Leukemia, Acute","Nonlymphoblastic Leukemia, Acute","Leukemia, Lymphocytic, Acute",[539,540,541,542,543,544,399,545,546,547],"Chronic Myelomonocytic Leukemia","Multiple Myeloma","Tumor-Associated Antigen","T-cell acute lymphoblastic leukemia","T cell immunotherapy","Myelodysplastic Syndrome","Engineered T cell receptor","Chronic Myeloid Leukemia","Adoptive T Cell Therapy",{"date":42,"type":43},{"date":45,"type":22},{"date":551,"type":22},"2029-04-30",{"name":49,"class":50},{"id":554,"slug":555,"hasResults":12,"nctId":556,"briefTitle":557,"officialTitle":558,"acronym":4,"eligibilityCriteria":559,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":560,"targetDuration":4,"studyType":23,"phases":562,"briefSummary":563,"conditions":564,"keywords":572,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":583,"startDateStruct":584,"completionDateStruct":586,"leadSponsor":588,"locationsCount":51},"100584158","phase-1-anti-mesothelin-tnaivescm-hyp218-tnhyp218-car-t-cells-in-participants-with-mesothelin-expressing-solid-tumors-including-mesothelioma-100584158","NCT06885697","Anti-Mesothelin TNaive\u002FSCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma","Phase 1 Study With Dose Expansion of the Anti-Mesothelin TNaive\u002FSCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria. For this protocol, treatment initiation is defined as the first day of lymphodepleting chemotherapy.\n\n* Participant must have unresectable, locally advanced, or metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors. For participants with mesothelioma only those with epithelioid or biphasic histology (with \\>80% epithelioid component) will be eligible. The diagnosis will be confirmed by the Laboratory of Pathology, CCR, NCI.\n* Participant must have progressed on at least one FDA-approved systemic therapy considered standard of care for their tumor type. There is no limit on the number of prior treatment regimens. Note: Given the aggressive nature of pancreatic cancer, otherwise eligible individuals with this cancer type can undergo leukapheresis before or while they are getting their frontline treatment as long as they meet all other inclusion criteria. However, TNhYP218 CAR T cells will only be administered after progression on first line standard of care therapy.\n* Participant must have at least 1 measurable lesion by RECIST version 1.1.\n* Tumor must have MSLN positivity of 2+ to 3+ in \\>= 50% cancer cells by immunohistochemistry on freshly collected biopsy or archival tissue.\n* Age \\>= 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Participants must have adequate organ and marrow function as defined below:\n\nSystem: Laboratory Value\n\nHematological\n\n* Hemoglobi: \\>=9 g\u002FdL(a)\n* absolute neutrophil count: \\>=1,500\u002FmcL\n* platelets: \\>=100,000\u002FmcL\n\nHepatic\n\n* total bilirubin: \\\u003C=2.5 X institutional ULN OR direct bilirubin ULN for participants with total bilirubin levels \\>1.5 X ULN\n* AST and ALT \\\u003C= 2.5 X institutional ULN (\\\u003C= 5 X ULN for participants with liver metastases)\n\nRenal\n\n* Creatinine OR: \\\u003C=1.5 X ULN OR\n* Calculated(b) creatinine clearance (GFR can also be used in place of creatinine or CrCl) \\>= 50 mL\u002Fmin for participant with creatinine levels \\> 1.5 X institutional ULN\n\nCoagulation\n\n* International normalized ratio (INR) OR prothrombin time (PT): \\\u003C=1.5 X ULN unless participant is receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended use of anticoagulants\n* Activated partial thromboplastin time (aPTT): \\\u003C=1.5 X ULN unless participant is receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended use of anticoagulants\n\nALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.\n\n1. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.\n2. Creatinine clearance (CrCl) should be calculated per institutional standard.\n\n   * Normal cardiac ejection fraction (\\>= 45% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram.\n   * Room air oxygen saturation of 90% or greater.\n   * Treatment-related toxicities from prior treatments must be resolved to \\\u003C= grade 2.\n   * Participants with CNS metastases, leptomeningeal disease or carcinomatous meningitis are eligible if they are asymptomatic, have completed their treatment for CNS disease and have recovered from the acute effects of radiation therapy or surgery prior to study entry. Participants must have radiographically stable CNS disease without associated edema at least three months prior to study entry. Additionally, participants have had to have discontinued corticosteroid treatment or non-prophylactic antiseizure medications for these metastases at least four weeks prior to study entry.\n   * Participants of child-bearing potential and participants who can father children must agree to use highly effective contraception or abstinence.\n   * Participants who are nursing or plan to nurse a child must agree to discontinue\u002Fpostpone nursing for the duration of study therapy and for 12 months after the administration of the cell product or for 4 months from the time no evidence of persistence\u002Fgene modified cells is documented in the participant s blood.\n   * Ability of participant to understand and the willingness to sign a written informed consent document.\n\n   EXCLUSION CRITERIA:\n\n   An individual who meets any of the following criteria will be excluded from participation in this study:\n   * Prior systemic therapy, an investigational therapy, radiation, and\u002For surgery within 14 days prior to leukapheresis and 21 days prior to lymphodepleting chemotherapy.\n   * Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.\n   * Participants with any form of primary immunodeficiency (e.g. severe combined immunodeficiency).\n   * Participants with active or history of autoimmune or immune mediated disease such as multiple sclerosis, lupus, inflammatory bowel disease, rheumatoid arthritis, or small vessel vasculitis. NOTE: Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.\n   * History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.\n   * Therapeutic doses of systemic corticosteroid therapy within 14 days prior to treatment initiation. Physiological doses of steroids (up to 5mg\u002Fday of prednisolone or equivalent) are allowed. Corticosteroid creams, ointments, and eye drops are allowed.\n   * Participants with lung fibrosis, inflammatory lung disease or evidence of pneumonitis on baseline imaging studies or medical history of these disorders.\n   * Participant has any other prior or concurrent malignancy with the following exceptions:\n\n     * Adequately treated basal cell or squamous cell carcinoma\n     * In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 12 months prior to initiation of study therapy.\n     * Treated non-melanoma skin cancer.\n     * Stage 0 or 1 melanoma completely resected at least 12 months prior to initiation of study therapy.\n     * Successfully treated organ-confined prostate cancer with no evidence of progressive disease based on PSA levels and are not on active therapy.\n     * A primary malignancy which has been completely resected and in complete remission for \\>= 5 years.\n   * Electrocardiogram showing a QTc interval \\> 450 msec in males and \\> 470 msec in females (\\> 80 msec for participants with bundle branch block). Either Fridericia s or Bazett s formula may be used to correct the QT interval.\n   * Participant has active infection with HIV, hepatitis B virus, HCV, or HTLV as defined below:\n\n     * Positive serology for HIV, HTLV-1, or HTLV-2.\n     * Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Participants who are hepatitis B surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation.\n     * Active hepatitis C infection as demonstrated by hepatitis C RNA test. Participants who are HCV antibody positive will be screened for HCV RNA by any reverse transcription PCR or branched DNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value.\n   * Participant is pregnant or intends to be pregnant during the required period of contraception for participants of childbearing potential.\n   * Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of treatment initiation\n   * Participants with a history of seizure disorder unless due to now treated metastatic lesions.\n   * Ongoing uncontrolled intercurrent illness, including but not limited to ongoing or active infection, that would impact participant safety or limit compliance with study requirements.",{"count":561,"type":22},100,[62],"Background:\n\nMesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN.\n\nObjective:\n\nTo test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma.\n\nEligibility:\n\nPeople aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment.\n\nDesign:\n\nParticipants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN.\n\nParticipants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein.\n\nParticipant s T cells will be modified in a lab to produce TNhYP218 CAR T cells.\n\nParticipants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment.\n\nTNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days.\n\nAfter discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy.\n\nLong-term follow-up will continue another 10 years....",[565,66,566,567,568,569,570,571],"Mesothelioma","Stomach Neoplasms","Pancreatic Neoplasms","Ovarian Neoplasms","Lung Neoplasms","Thymus Neoplasms","Colonic Neoplasms",[573,574,575,576,577,578,579,580,581,582],"Peritoneal Mesothelioma","Thymic Carcinoma","Colon Cancer","Gastric Cancer","Lung Cancer","Ovarian Cancer","Pancreatic Cancer","mesothelin expressing solid tumors","CAR T cell therapy","Gene Therapy",{"date":42,"type":43},{"date":585,"type":43},"2025-07-08",{"date":587,"type":22},"2044-06-01",{"name":49,"class":50},{"id":590,"slug":591,"hasResults":12,"nctId":592,"briefTitle":593,"officialTitle":594,"acronym":4,"eligibilityCriteria":595,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":596,"targetDuration":4,"studyType":23,"phases":597,"briefSummary":598,"conditions":599,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":607,"startDateStruct":608,"completionDateStruct":610,"leadSponsor":612,"locationsCount":613},"100582229","phase-1-testing-the-addition-of-an-anti-cancer-drug-triapine-to-the-usual-radiation-therapy-for-recurrent-glioblastoma-or-astrocytoma-100582229","NCT06860594","Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma","A Phase I Trial Combining Triapine With Radiation Therapy for Recurrent Glioblastoma or Astrocytoma","Inclusion Criteria:\n\n* Patients must have histologically, molecularly, or cytologically confirmed recurrent astrocytic tumors including:\n\n  * GBM or variants, IDH-wildtype, grade 2-4 (standard curative measures available or not)\n  * Astrocytoma, IDH-mutant, grade 2-4 (standard curative measures available or not)\n  * Diffuse midline gliomas, including pediatric-type H3 G34 or E3 K27 mutant tumors.\n* Tumors ≤ 6 cm in maximal diameter.\n\n  * Patients who had recent resection for recurrent tumor must have measurable disease.\n* Patients must have at least a 6-month break from last dose of radiation therapy.\n\nRe-irradiation within 6 months may increase risk for radiation necrosis\u002Fedema, which will affect toxicity assessment and patient safety. Additionally, GBM and other high-grade astrocytic tumors can exhibit pseudo-progression within 6 months from completing definitive, 1st line radiation therapy, and re-irradiation during this period will increase risk for misattribution of effect.\n\n* Prior history of standard dose radiation for gliomas of 59.4-60 gray (Gy) in 1.8-2 Gy per fraction (or equivalent or lower) is allowed.\n* Patients who received non-standard radiation dose regimen (e.g., 40 Gy, 34-35 Gy, 25 Gy) or stereotactic radiosurgery are eligible as long as there is at least one of the following:\n\n  * A new tumor outside the original radiotherapy field as determined by the investigator.\n  * There is histologic confirmation of tumor on biopsy or resection.\n  * Imaging findings are consistent with true progressive disease (on standard MRI sequences, MRI spectroscopy\u002Fperfusion, or nuclear medicine imaging).\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of triapine in patients \\\u003C 18 years of age, children are excluded from this study.\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).\n* Absolute neutrophil count ≥ 1,500\u002FmcL.\n* Hemoglobin ≥ 8 g\u002FdL.\n* Platelets ≥ 100,000\u002FmcL.\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) ≤ 3 x institutional ULN.\n* Creatinine ≤ 1.5 x ULN OR glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin\u002F1.73 m\\^2.\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better.\n* Patients must be able to swallow whole capsules.\n* Patients must be able to undergo MRIs with contrast. Patients with non-compatible devices with MRI can be eligible if CT scans of sufficient quality are obtained. However, patients without non-compatible devices may not use CT scans to meet this requirement.\n* The effects of triapine on the developing human fetus are unknown. For this reason and because ribonucleotide reductase (RNR) inhibitor agent and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 12 months after finishing study treatment. People of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of human chorionic gonadotropin \\[HCG\\]) within 2 weeks of registration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 months after completion of triapine administration.\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia.\n* Patients who are receiving any other investigational agents.\n* Patients who are actively taking medications that are known to induce methemoglobinemia (e.g. sulfonamides, nitrofurans, anti-malarials \\[primaquine, chloroquine\\], cyclophosphamide, and ifosfamide).\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine.\n* Patients with known G6PD deficiency. Testing for G6PD deficiency is not required.\n* Patients with uncontrolled intercurrent illness, active infections, or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.\n* Pregnant women are excluded from this study because triapine is a RNR inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine, breastfeeding should be discontinued if the mother is treated with triapine. These potential risks may also apply to the radiation used in this study.",{"count":352,"type":22},[62],"This phase I trial tests the safety, side effects, and best dose of triapine in combination with radiation therapy in treating patients with glioblastoma or astrocytoma that has come back after a period of improvement (recurrent). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving triapine in combination with radiation therapy may be safe, tolerable, and\u002For effective in treating patients with recurrent glioblastoma or astrocytoma.",[600,601,602,603,604,605,606],"Astrocytoma, IDH-Mutant, Grade 2","Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant","Recurrent Adult Diffuse Midline Glioma, H3 K27-Mutant","Recurrent Astrocytoma, IDH-Mutant","Recurrent Astrocytoma, IDH-Mutant, Grade 3","Recurrent Astrocytoma, IDH-Mutant, Grade 4","Recurrent Glioblastoma, IDH-Wildtype",{"date":42,"type":43},{"date":609,"type":43},"2025-07-30",{"date":611,"type":22},"2027-06-30",{"name":49,"class":50},43,{"id":615,"slug":616,"hasResults":12,"nctId":617,"briefTitle":618,"officialTitle":619,"acronym":4,"eligibilityCriteria":620,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":621,"enrollmentInfo":622,"targetDuration":4,"studyType":199,"phases":4,"briefSummary":623,"conditions":624,"keywords":625,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":628,"startDateStruct":629,"completionDateStruct":630,"leadSponsor":632,"locationsCount":51},"100573284","experience-and-management-of-cancer-screening-related-anxiety-in-fanconi-anemia-100573284","NCT06744283","Experience and Management of Cancer Screening-Related Anxiety in Fanconi Anemia","The Experience and Management of Cancer Screening-Related Anxiety in Fanconi Anemia: an Ethnographic Study","* INCLUSION CRITERIA:\n\nParticipants enrolled in the FACSS protocol who are 18 years of age or older are eligible for inclusion in this study. Clinical visits eligible for ethnographic observation are limited to initial visits (medical history and physical examination) and\u002For return of results visits happening in the context of their first visit to the NIH Clinical Center for the FACSS protocol and\u002For annual return visits.\n\nTo be eligible, the following requirements must be met:\n\n* Ability for the participant to speak, read, and\u002For write in English to understand and agree to a verbal consent.\n* Participants must have a diagnosis of FA.\n* Participants must be 18 years of age or older.\n\nEXCLUSION CRITERIA:\n\n* Individuals who do not meet eligibility criteria.\n* Subjects who declined or opted out of allowing their data to be used for future research.\n* Subjects who orally declined to have Dr. Emily Pearce shadow their clinical center visits.\n* No other exclusionary criteria apply.","100 Years",{"count":60,"type":22},"Background:\n\nFanconi anemia (FA) is a rare, inherited cancer syndrome. FA causes a range of physical issues. Children with FA may have abnormal features; these may include a small head and eyes and issues with their internal organs. Young adults have a much higher risk of cancer. To screen for these cancers, people with FA may need to pursue many visits with different doctors. This constant need for cancer screening may cause anxiety for people with FA.\n\nObjective:\n\nTo learn more about anxiety related to cancer screenings in people with FA.\n\nEligibility:\n\nAdults aged 18 years and older with FA. They must also be enrolled in FACSS. FACSS is a study that screens people with FA for cancer every year.\n\nDesign:\n\nAll data gathered for this study will occur during routine FACSS visits. No other visits are needed.\n\nAn observer will be in the room during participants FACSS visits. The observer and participant will have a polite introduction. After that, the observer will not interact with participants in any way.\n\nThe observer will note details about the participants, such as:\n\n* Body language.\n* Worries about screening.\n* Comments that suggest anxiety or depression.\n* Clinical environment, such as d(SqrRoot)(Copyright)cor and temperature.\n* Accessibility issues. These can include lights and noises as well as ease of traveling around the clinic center.\n* Evidence of social support, such as engaging in the FA community.\n* Challenges they ve had in FACSS.\n* Their motivation to participate in FACSS.\n* Relationship dynamics among clinic staff, participants, and their care partners.\n\nData will also be collected from FACSS visit notes dating back to December 2024 and from participants medical records.",[480],[626,480,488,627],"Uncertainty","Screening",{"date":42,"type":43},{"date":45,"type":22},{"date":631,"type":22},"2027-01-30",{"name":49,"class":50},{"id":634,"slug":635,"hasResults":12,"nctId":636,"briefTitle":637,"officialTitle":638,"acronym":4,"eligibilityCriteria":639,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":640,"targetDuration":4,"studyType":23,"phases":642,"briefSummary":643,"conditions":644,"keywords":4,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":649,"startDateStruct":650,"completionDateStruct":652,"leadSponsor":654,"locationsCount":655},"100554403","immunotherapy-after-surgery-for-people-who-have-no-remaining-cancer-cells-after-standard-treatment-for-early-stage-non-small-cell-lung-cancer-insight-trial-100554403","NCT06498635","Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial","Randomized Phase III Trial INcorporating Pathologic Complete ReSponse in Participants With Early StaGe Non Small Cell Lung Cancer to Optimize ImmunotHerapy in The AdjuvanT Setting (INSIGHT)","Inclusion Criteria:\n\n* Participants must have histologically or cytological confirmed diagnosis of clinical stage II-IIIB (excluding clinical N3 disease) non-small cell lung cancer (NSCLC)\n* Participants must have had a complete (R0) resection of NSCLC (with appropriate lymph node sampling as defined by the National Comprehensive Cancer Network \\[NCCN\\] guidelines) within 84 days (12 weeks) prior to randomization. Acceptable types of surgical resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge resection is not allowed.\n\n  * Note the NCCN guidelines: N1 and N2 node resection and mapping is a routine component of lung cancer resections. It is recommended at a minimum one N1 and three N2 stations is sampled or complete lymph node dissection. Formal ipsilateral mediastinal lymph node dissection is indicated for participants undergoing resection for N2 disease\n* Participants must have a pathologic complete response (pCR) (no viable tumor in the resected specimen or lymph nodes), as determined by local pathology review\n* Participants must have a PD-L1 status result (e.g. \\[\\\u003C 1% versus \\>= 1% or unknown\\])\n* Participants must not have known EGFR mutations, or ALK gene fusion\n* Participants must have received at least two cycles of neoadjuvant platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be Food and Drug Administration (FDA) approved and standard of care as listed in NCCN guidelines\n* Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while receiving treatment on this study\n* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 28 days prior to randomization\n* Participants must not have medical contraindications or severe adverse events to receiving anti-PD-1 or anti-PD-L1 therapy\n* Participants must not have received post-operative radiation therapy (PORT) for NSCLC\n* Participants must not have any unresolved toxicity National Cancer Institute (NCI) CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, and vitiligo. Note, participants with grade ≥2 neuropathy may be included at the discretion of the treating investigator. Note, participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the treating investigator\n* Participant must be ≥ 18 years old at time of study entry\n* Participants must have body weight \\> 30 kg\n* Participant must have Zubrod performance status of 0-2\n* Participant must have a complete medical history and physical exam within 28 days prior to randomization\n* Hemoglobin \\> 9.0 g\u002FdL (within 28 days prior to randomization)\n* Absolute neutrophil count ≥ 1.5 x 10\\^3\u002FuL (within 28 days prior to randomization)\n* Platelets ≥ 100 x 10\\^3\u002FuL (within 28 days prior to randomization)\n* Total bilirubin ≤ 1 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to randomization)\n* Aspartate transaminase (AST)\u002Falanine transaminase (ALT) ≤ 3 × institutional ULN (within 28 days prior to randomization)\n* Participants must have a calculated creatinine clearance ≥ 40 mL\u002Fmin using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to randomization. For creatinine clearance formula see the tools on the Clinical Research Associate (CRA) Workbench https:\u002F\u002Ftxwb.crab.org\u002FTXWB\u002FTools.aspx\n* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator\n* Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization\n* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated\n* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated\n* Participants must not have had an organ transplant\n* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Participant must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed\n* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of \"reproductive potential.\" In addition to routine contraceptive methods, \"effective contraception\" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation\u002Focclusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy\n* Participants must not have received a live or live attenuated vaccine within 28 days prior randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster, yellow fever rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and coronavirus disease 19 (COVID-19) vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated, and are not allowed\n* Participants must be offered the opportunity to participate in specimen banking\n* Participants who can complete FACT-L, FACT-BRM, and PRO-CTCAE questionnaires forms in English, or Spanish must agree to participate in the patient-reported outcome study\n* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system\n* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines\n* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations",{"count":641,"type":22},306,[329],"This phase III trial compares durvalumab to the usual approach (patient observation) after surgery for the treatment of patients with early-stage non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The usual approach for patients who are not in a study is to closely watch a patient's condition after surgery and to have regular visits with their doctor to watch for signs of the cancer coming back. Usually, patients do not receive further treatment unless the cancer returns. This study will help determine whether this different approach with durvalumab is better, the same, or worse than the usual approach of observation. Giving durvalumab may help patients live longer and prevent early-stage non-small cell lung cancer from coming back as compared to the usual approach.",[645,646,647,648],"Lung Non-Small Cell Carcinoma","Stage II Lung Cancer AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIB Lung Cancer AJCC v8",{"date":42,"type":43},{"date":651,"type":43},"2025-04-01",{"date":653,"type":22},"2039-07-15",{"name":49,"class":50},278,{"id":657,"slug":658,"hasResults":12,"nctId":659,"briefTitle":660,"officialTitle":661,"acronym":4,"eligibilityCriteria":662,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":663,"targetDuration":4,"studyType":23,"phases":665,"briefSummary":666,"conditions":667,"keywords":673,"overallStatus":313,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":684,"startDateStruct":685,"completionDateStruct":686,"leadSponsor":688,"locationsCount":51},"100553545","study-of-preoperative-radiation-therapy-in-participants-with-resectable-recurrent-abdominal-adrenocortical-carcinoma-100553545","NCT06487481","Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma","A Phase I Dose-escalation Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma","* INCLUSION CRITERIA:\n* Age \\>= 18 years\n* Pathological confirmation of ACC by the Laboratory of Pathology, NCI. Note: Confirmation may be done from archival sample; fresh tissue is not required unless otherwise acquired for clinical purposes.\n* Measurable disease by RECISTv1.1. criteria at enrollment\n* Evidence of recurrent ACC amenable to surgical resection that can be performed at NIH Clinical Center (CC)\n* Must be suitable for external beam radiotherapy AND surgery in the opinion of the treating investigator (e.g., based on clinical history and imaging)\n* Participants with metastatic ACC outside the area(s) to be exposed to investigational treatments (e.g., liver parenchyma, lung\\[s\\], or bone\\[s\\]) must have disease that is amendable for a complete resection and\u002For catheter-based and\u002For radiation-based ablation.\n* Mitotane therapy- Participants may be receiving mitotane currently, have received it in the past, or never have received mitotane. However, participants will be evaluated in separate cohorts based on mitotane use and, as enrollment is sequential, not all participants may be eligible for the study at all times. Note: Participants with a history of mitotane use may continue on study at the discretion of the treating investigator. Participants will not initiate mitotane on study.\n* Participants must agree to undergo tumor biopsy of easily accessible tumor sites prior to study treatment.\n* Performance Status (ECOG) 0-2\n* Adequate organ function, including:\n\n  * Hemoglobin \\>= 9.0 gm\u002FdL\n  * ANC \\>= 1,500\u002Fmm\\^3\n  * Platelets \\>= 75,000\u002Fmm\\^3\n  * AST and ALT \\\u003C= 3 x Upper Limit Normal (ULN)\n  * Bilirubin \\\u003C= 2 x ULN\n  * Creatinine within normal institutional limits or creatinine clearance \\>60 mL\u002Fmin\u002F1.73 m\\^2 for participants with creatinine levels above institutional normal calculated using eGFR.\n* Individuals of childbearing potential must agree to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to RT and continue until at least 4 months following cytoreduction surgery.\n* Nursing (including breastfeeding) participants must agree to discontinue nursing prior to RT and continue until at least 4 months following cytoreductive surgery.\n* Ability of participant to understand and willingness to sign a written informed consent document\n* Participants must agree to co-enroll in tissue collection protocol 09C0242 \"Prospective comprehensive molecular analysis of endocrine neoplasms.\"\n\nEXCLUSION CRITERIA:\n\n* Primary ACC or suspicious\u002Findeterminate adrenal tumor without pathological confirmation\n* Prior abdominal radiation therapy\n* Participants who have received chemotherapy, immunotherapy, investigational therapy, or radiotherapy treatment within the last 4 weeks prior to starting treatment and\u002For have not recovered from toxicities to less than grade 2 CTCAE.\n* Infection requiring parenteral antibiotics\n* Suspected or proven ACC peritoneal metastasis\n* Pre-existing known or suspected radiation sensitivity syndromes\n* Prohibitive condition(s) to diagnostic laparoscopy\n* Participants who have an unacceptable risk for a major surgical procedure such as participants with high risks for major cerebro-cardiovascular (such as those who had doxorubicin exposure as based on screening echocardiogram and ECG) and pulmonary complications and those with estimated perioperative mortality greater than 15% per ACS NSQIP Surgical Risk calculator.\n* Participants receiving other investigational therapies\n* Participant pregnancy\n* Active systemic infections, coagulation disorders, or other major medical illnesses such as uncontrolled diabetes mellitus, uncontrolled hypertension (persistently grade 2 or worse), active severe cerebro-cardio-pulmonary diseases, and acute major organ dysfunction.\n* Acute intraabdominal conditions such as obstruction or peritonitis at the time of the evaluation or surgery.\n* Evidence at screening of or currently active CNS metastasis within 6 months of RT; participants with history of treated brain metastases with intracranial recurrence within 6 months prior to treatment. Note: Participants with any signs or symptoms suggestive of previously undiagnosed brain metastasis at screening or with a history of brain metastasis should receive imaging at screening; otherwise, imaging is not required.\n* HIV-positive participants with CD4 below 200 or who are not on anti-retroviral therapy\n* Participants who have a history of another primary malignancy from which the participant has been disease-free for \\\u003C 3 years at the time of enrollment.",{"count":664,"type":22},32,[62],"Background:\n\nAdrenocortical carcinoma (ACC) is a rare cancer of the adrenal glands. ACC often returns after tumors are removed with surgery. Less than 35% of people with ACC survive 5 years after diagnosis.\n\nObjective:\n\nTo test a new type of external beam RT before surgery in people with ACC.\n\nEligibility:\n\nPeople aged 18 years and older with ACC that came back after treatment but may be safely removed with surgery.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have imaging scans. A small sample of tumor tissue may be collected if one is not available. They will undergo laparoscopy: Small incisions will be made in the abdomen so that a thin tube with a light and camera can be inserted to view the organs.\n\nRT comes from a machine that aims radiation at tumors. Participants will receive preoperative RT in daily fractions over approximately 2-3 weeks, followed by a planned surgical resection about 4 weeks after the completion of RT. Visits will last 30 to 60 minutes.\n\nParticipants will undergo surgery to remove their tumors about 4 weeks after they finish RT. They will stay in the hospital 1 to 3 weeks after surgery.\n\nParticipants will have follow-up visits for 10 years after surgery.",[668,669,670,671,672],"Adrenocortical Carcinoma (ACC)","Recurrent Adrenocortical Carcinoma (ACC)","Recurrent Abdominal Adrenocortical Carcinoma (ACC)","Carcinoma, Adrenocortical","Carcinoma, Adrenal Cortical",[674,675,676,677,678,679,680,681,682,683],"external beam radiation therapy (EBRT)","abdominal adrenocortical carcinoma (ACC)","preoperative radiation","Mitotane","Maximum Tolerated Dose (MTD)","Surgical Resection","in-field intraabdominal progression-free survival (PFS)","out-of-field intraabdominal progression-free survival (PFS)","DNA damage repair markers","oxidative stress response",{"date":42,"type":43},{"date":45,"type":22},{"date":687,"type":22},"2040-12-01",{"name":49,"class":50},""]