[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Therapeutic Advances in Childhood Leukemia Consortium\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":101},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,40,70],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":4},"100646824","phase-2-trial-of-revumenib-plus-fla-chemotherapy-for-children-with-relapsed-or-refractory-nup98-rearranged-aml-100646824",false,"NCT07686107","Trial of Revumenib Plus FLA Chemotherapy for Children With Relapsed or Refractory NUP98-rearranged AML.\"","T2023-004 Phase 2 Trial of Revumenib (SNDX-5613) in Combination With FLA Chemotherapy for Children With Relapsed or Refractory NUP98-rearranged Acute Myeloid Leukemia","Inclusion Criteria:\n\nAge Patients must be \\> 1 year and \\\u003C 22 years of age at time of enrollment.\n\nDiagnosis Patients must have NUP98-r AML (according to WHO Classification of Hematolymphoid Tumors (5th Edition)) that is either refractory to or is in first relapse following initial therapy. Documentation of prior known NUP98-r AML is sufficient.\n\nDefinition of relapsed disease:\n\n* Recurrent disease with ≥ 5% leukemic blasts by morphology in the bone marrow after having achieved morphologic remission (morph-CR). Patients who have received any other re-induction therapy following relapse will not be eligible.\n* Morph-CR is defined as attainment of an M1 bone marrow (\\\u003C 5% morphologic leukemic blasts) no evidence of circulating leukemic blasts or extramedullary disease and with recovery of peripheral blood counts (ANC ≥ 500\u002FµL and platelet count ≥ 50,000\u002FµL).\n\nDefinition of primary refractory disease:\n\nRefractory disease with ≥ 5% leukemic blasts by morphology in the bone marrow after one attempt at remission induction, which may consist of up to two different therapy courses (e.g., COG AAML1831 de novo therapy including Induction I and Induction II). Patients must not have received more than one remission induction remission attempt.\n\nWhite Blood Cell Count:\n\nWhite blood cell count must be \\\u003C25,000 cells\u002FuL at the time of enrollment on the study. Cytoreduction with leukapheresis, hydroxyurea, and\u002For cytarabine (up to a total dose of 500 mg\u002Fm\\^2) prior to enrollment is allowed.\n\nPerformance Level Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (\\> 50 Lansky or Karnofsky score). Use Karnofsky for patients \\> 16 years of age and Lansky for patients ≤ 16 years of age (Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\nCNS Disease Patients may have status of CNS1, CNS2, or asymptomatic CNS3 disease. Patients with symptomatic CNS 3 disease are ineligible.\n\nHIV-Infection HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial, provided antiretroviral therapy does not have clinically significant drug-drug interactions with revumenib.\n\nPrior Therapy:\n\nPatients must have recovered from all prior treatment-related toxicities to grade ≤1 or the patient's baseline and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.\n\n1. Cytotoxic Chemotherapy: Must not have received within 14 days of entry onto this study, except for hydroxyurea or cytarabine\n\n   NOTE: Cytoreduction with hydroxyurea and cytarabine (up to a total dose of 500 mg\u002Fm2) must be discontinued prior to the start of protocol therapy.\n2. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before enrollment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.\n3. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors).\n4. Hematopoietic Growth Factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for short acting growth factor.\n5. Radiation Therapy (RT):\n\n   * 14 days have elapsed for local palliative RT (small port);\n   * ≥ 84 days must have elapsed if prior craniospinal RT or if 50% radiation of pelvis;\n   * ≥ 42 days must have elapsed if other substantial BM radiation.\n6. Stem Cell Infusions:\n\n   * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without TBI) or boost infusion (any stem cell product; not including DLI);\n   * No evidence of graft versus host disease (GVHD).\n7. Cellular Therapy: ≥ 28 days after the completion of DLI (donor lymphocyte infusion) or any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.).\n\nNOTE: Potential subjects who have received an intervention intended to treat their primary malignancy which does not fall into one of the above categories will require a minimum 30 day washout from that intervention and the patient must be discussed with the Study Chair or designee who may determine a longer washout period as necessary.\n\nNOTE: Intrathecal chemotherapy: No waiting period is required for patients having received any combination of intrathecal therapy (cytarabine, methotrexate, and\u002For corticosteroids).\n\nOrgan Function Requirements\n\nAdequate Renal Function Defined as:\n\nPatient must have a calculated creatinine clearance or radioisotope GFR ≥ 60ml\u002Fmin\u002F1.73m2.\n\nAdequate Liver Function Defined as:\n\n* Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5x institutional upper limit of normal for age (unless attributable to leukemic involvement), and\n* SGPT (ALT) and SGOT (ALT) must be ≤3x institutional upper limit of normal. Patients with ALT and AST ≥ 3x ULN attributable to leukemic involvement of the liver are eligible as long as both are ≤5x ULN.\n\nAdequate Cardiac Function at Screening, Defined as:\n\n* Ejection fraction (EF) of ≥ 50% or if EF unavailable, shortening fraction (SF) ≥ 28% by echocardiogram. AND\n* Corrected QT (using Fridericia's correction \\[QTcF\\]) interval \\\u003C 450 msecs. See Appendix II for directions on calculating QTcF.\n\nNOTE: There are no specific electrolyte parameters for eligibility. However, it should be noted that, to limit QTc prolongation risk, patients must maintain adequate potassium and magnesium levels to initiate and continue revumenib on protocol therapy. See section 4.1.2.1 for electrolyte monitoring.\n\n.\n\nReproductive Function\n\n* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 72 hours prior to enrollment.\n* Female patients with infants must agree not to breastfeed their infants while on this study and for one week after the last revumenib dose.\n* Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for up to 4 months (16 weeks) after the last dose of revumenib.\n\nExclusion Criteria:\n\nIsolated Extramedullary Disease: Patients with isolated extramedullary disease are ineligible.\n\nPrior diagnosis of acute lymphoblastic leukemia: Patients experiencing lineage switch to AML will not be eligible for this study.\n\nCNS3 Disease with clinical signs or neurologic symptoms suggestive of CNS leukemia at time of relapse, such as facial nerve palsy, brain\u002Feye involvement or hypothalamic syndrome.\n\nInfection: Patients with documented active, uncontrolled infection at the time of study enrollment.\n\nPatients are excluded if they have:\n\n* Positive blood culture within 48 hours of study enrollment;\n* Fever above 38.2⁰C within 48 hours of study enrollment with clinical signs of infection. NOTE: Fever that is determined to be due to tumor burden does NOT exclude patients if there are documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.\n* A positive fungal culture within 30 days of study enrollment.\n* Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections does not exclude patients.\n\nCardiac: Patients with a history of congenital prolonged QT syndrome, congestive heart failure, or uncontrolled arrhythmia in the past 6 months prior to study enrollment.\n\nGastrointestinal issues: Patients with gastrointestinal issues of the upper gastrointestinal tract that might affect oral drug absorption.\n\nPrior menin inhibitor therapy\n\nPatients with active GVHD are ineligible to enroll. Patients who are receiving systemic cyclosporine, tacrolimus, or other agents to prevent or treat either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible to enroll on the trial. Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible.\n\nConcomitant Medications CYP3A4 Inhibitors\u002FInducers: Systemically administered moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors should be discontinued for at least 5 half-lives or 7 days prior to enrollment (whichever is later) with the following exceptions: itraconazole, ketoconazole, posaconazole, or voriconazole.\n\nCorticosteroids: Patients who are receiving systemic corticosteroids are not eligible except when given as physiologic dosing (prednisone equivalent of ≤ 10 mg\u002Fday if ≥18 years and ≤ 10 mg\u002Fm2\u002Fday for patients \\\u003C 18 years is allowed).\n\nInvestigational Drugs: Patients who are receiving another investigational drug (for a time frame less than the 5 half-life periods of the respective investigational drug) are not eligible.\n\nQTc Prolonging Agents: Medications with a known risk of Torsades de Pointes (TdP) are prohibited, with the exception of drugs that are used as standard supportive therapies (listed below). Medications with a possible or conditional risk of TdP are allowed. Consult CredibleMeds® at https:\u002F\u002Fcrediblemeds.org\u002F for risk classifications.\n\nMedications with a known risk of TdP used as standard supportive therapies that are allowed for concomitant use: azithromycin, ciprofloxacin, fluconazole, levofloxacin, methadone (allowed if chronic, scheduled use \\> 2 weeks prior to revumenib initiation; do not initiate methadone during protocol treatment), ondansetron, pentamidine, and propofol.\n\nSee Appendix II for Cardiac Monitoring Guidelines Patients with a contraindication or unable to tolerate at least one of the following medications utilized for antifungal prophylaxis: itraconazole, ketoconazole, posaconazole, or voriconazole.\n\nPatients will be excluded if they have a known allergy to any of the drugs used in the study.\n\nPatients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.\n\nPatients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.\n\nPatients with cirrhosis based on PELD and Child-Pugh scoring systems with moderate to severe hepatotoxicity are excluded.","ALL","1 Year","22 Years",{"count":20,"type":21},24,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The goal of this clinical trial is to learn if Revumenib in combination with Fludarabine and Cytarabine can treat children with NUP98-rearranged relapsed or refractory Acute Myeloid Leukemia. The main question it aims to answer is:\n\nWhat is the Best Overall Response Rate by morphologic response criteria after up to two cycles of revumenib in combination with fludarabine and cytarabine (FLA) chemotherapy?\n\nParticipants will receive up to two cycles of Revumenib in combination with fludarabine and cytarabine with intrathecal triple therapy. Participant may also receive a stem cell transplant followed by Revumenib monotherapy if it is necessary.\n\nUp to 27 children and young adults will be enrolled.",[27],"Leukemia, Myeloid, Acute","NOT_YET_RECRUITING","2026-07-20",{"date":31,"type":32},"2026-07-22","ACTUAL",{"date":34,"type":21},"2026-08-31",{"date":36,"type":21},"2030-12-31",{"name":38,"class":39},"Therapeutic Advances in Childhood Leukemia Consortium","OTHER",{"id":41,"slug":42,"hasResults":11,"nctId":43,"briefTitle":44,"officialTitle":45,"acronym":4,"eligibilityCriteria":46,"healthyVolunteers":11,"sex":16,"minAge":47,"maxAge":48,"enrollmentInfo":49,"targetDuration":4,"studyType":22,"phases":51,"briefSummary":53,"conditions":54,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":69},"100504540","phase-1-a-phase-iii-study-of-trametinib-and-azacitidine-for-patients-with-newly-diagnosed-juvenile-myelomonocytic-leukemia-100504540","NCT05849662","A Phase I\u002FII Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia","Risk Stratified Treatment for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia: A Phase I\u002FII Non-randomized Study of Trametinib and Azacitidine With or Without Chemotherapy (IND #164058)","Inclusion Criteria:\n\nAge\n\n• Patients must be ≥ 1 month and ≤21 years of age at enrollment.\n\nDiagnosis • Patients must meet the 2022 International Consensus Classification criteria for JMML. The diagnosis is made based on the following criteria:.\n\nClinical and hematologic features (the first 2 features are present in most cases; the last 2 are required):\n\n* Peripheral blood monocyte count ≥ 1 × 109\u002FL\\*\n* Splenomegaly†\n* Blast percentage in PB and BM \\\u003C 20%\n* Absence of BCR::ABL1\n\n  * This monocyte threshold is not reached in approximately 7% of cases. †Splenomegaly is absent in 3% of cases at presentation.\n\nII. Genetic studies (1 finding required):\n\n* Somatic mutation in PTPN11‡ or KRAS‡ or NRAS‡ or RRAS or RRAS2‡\n* Clinical diagnosis of neurofibromatosis type 1 or germline NF1 mutation and loss of heterozygosity of NF1 or somatic biallelic loss of NF1\n* Germline CBL mutation and loss of heterozygosity of CBL, or somatic mutation(s) in CBL§\n\n  * Germline mutations (indicating Noonan syndrome) need to be excluded. §Occasional cases with heterozygous splice site mutations.\n\nPerformance Level\n\n* Karnofsky \\> 50% for patients ≥ 16 years of age\n* Lansky \\> 50% for patients \\\u003C 16 years of age.\n\nPrior Therapy\n\n* No prior leukemia directed therapy is permitted with the exception of:\n\n  1. Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of trametinib.\n  2. Cytoreduction with 6-mercaptopurine (6-MP) 6-MP can be initiated and continued for up to 72 hours prior to the start of trametinib.\n  3. Intrathecal (IT) cytarabine, IT methotrexate or triple IT therapy (cytarabine, methotrexate and hydrocortisone) within 7 days of enrollment as part of a diagnostic evaluation.\n\n     No prior hematopoietic stem cell transplant is permitted.\n\n     Adequate Renal Function Defined as:\n* Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73m2 OR a normal serum creatinine based on age\u002Fgender in the chart below:\n\nMaximum Serum Creatinine (mg\u002FdL):\n\n* 1 month to \\\u003C 6 months old - Male: 0.4, Female 0.4\n* 6 months to \\\u003C1 year old - Male 0.5, Female 0.5\n* 1 to \\\u003C 2 years old - Male: 0.6, Female: 0.6\n* 2 to \\\u003C 6 years old - Male:0.8, Female: 0.8\n* 6 to \\\u003C 10 years old - Male: 1, Female: 1\n* 10 to \\\u003C 13 years old - Male: 1.2, Female: 1.2\n* 13 to \\\u003C 16 years old - Male: 1.5, Female: 1.4\n* ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.\n\nAdequate Liver Function Defined as:\n\n* Direct bilirubin \\\u003C 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) \\\u003C 5 x ULN for age.\n* The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia and will not be evaluable for hepatotoxicity. This must be reviewed and approved by the study chair or vice chair.\n\nAdequate Cardiac Function Defined as:\n\n* Ejection fraction of \\> or = to 50% by echocardiogram, OR\n* Ejection fraction of \\> or = to 50% by radionuclide angiogram (MUGA).\n\nReproductive Function\n\n* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.\n* Female patients with infants must agree not to breastfeed their infants while on this study.\n* Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.\n\nExclusion Criteria:\n\n* Patients cannot have a known allergy to any of the drugs used in the study.\n* Patients cannot have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs\u002Fsymptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.\n* Patients cannot have a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.\n* Patients cannot have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.\n* Patients cannot have a clinical or molecular diagnosis of Noonan syndrome. Note: patients with either neurofibromatosis type 1 or Casitas B-lineage lymphoma (CBL) syndrome (also known as Noonan-like syndrome), are eligible to enroll. Patients with Down syndrome are excluded from the study.\n* Patient cannot have had prior use of hematopoietic growth factors, biologics (anti-neoplastic agent), or XRT.\n* Patients cannot be taking any medications for treatment of left ventricular systolic dysfunction.\n* Patients cannot have a history of or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).\n* Patients cannot have had prior use of any MEK inhibitor.","1 Month","21 Years",{"count":50,"type":21},58,[52,24],"PHASE1","This clinical trial will test the safety and efficacy of combining trametinib and azacitidine in patients with juvenile myelomonocytic leukemia (JMML). Newly diagnosed lower-risk JMML patients will receive trametinib and azacitidine. High-risk JMML patients will receive trametinib, azacitidine, fludarabine, and cytarabine.",[55,56,57,58,59],"Leukemia, Juvenile Myelomonocytic","JMML","JCML","Neurofibromatosis 1","CBL Syndrome","RECRUITING","2026-04-10",{"date":63,"type":32},"2026-04-15",{"date":65,"type":32},"2024-10-11",{"date":67,"type":21},"2029-12",{"name":38,"class":39},19,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":48,"enrollmentInfo":77,"targetDuration":4,"studyType":22,"phases":79,"briefSummary":80,"conditions":81,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":92,"lastUpdatePostDateStruct":93,"startDateStruct":95,"completionDateStruct":97,"leadSponsor":99,"locationsCount":100},"100475887","phase-1-tagraxofusp-in-pediatric-patients-with-relapsed-or-refractory-cd123-expressing-hematologic-malignancies-100475887","NCT05476770","Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies","A Phase I Study of Tagraxofusp With or Without Chemotherapy in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies","Inclusion Criteria:\n\nAge\n\n* Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment.\n\nDiagnosis\n\n* Relapsed and\u002For refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma).\n* Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution.\n\nDisease Status:\n\nMonotherapy, Part 1\n\n* Second or greater relapse; or\n* Refractory after 2 or more chemotherapy cycles; or\n* First relapse after primary chemotherapy-refractory disease; or\n* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles\n\nCombination therapy, Part 2\n\n* First or greater relapse; or\n* Refractory after 2 or more chemotherapy cycles; or\n* BPDCN in first relapse or refractory after 1 or more chemotherapy cycles\n\nFor relapsed\u002Frefractory leukemia, patients must have:\n\n* \\>5% blasts in the bone marrow aspirate or biopsy by morphology or flow cytometry\n* Patients with 1% - 5% blasts are eligible for Part 2, Cohort C (only), if A single bone marrow sample with flow cytometry and at least one other test (e.g. karyotype, FISH, PCR, or NGS) shows ≥ 1% leukemic blasts and\u002For flow cytometry demonstrates a stable or rising level of disease on two serial bone marrows.\n\nFor relapsed\u002Frefractory non-Hodgkin or Hodgkin lymphoma, patients must have:\n\n* Histologic verification of relapse\n* Measurable disease documented by radiographic criteria or bone marrow\n* Patients in Part 1 may have sites of non-CNS extramedullary disease, but no CNS disease. Patients in Part 2 may have CNS disease and\u002For other non-CNS extramedullary disease. No cranial irradiation is allowed during the protocol therapy.\n* Patients with Down syndrome are eligible to participate in Part 1 only.\n\nPerformance Level\n\n* Karnofsky \\> 50% for patients \\> 16 years of age and Lansky \\> 50% for patients ≤ 16 years of age (See Appendix I for Performance Scales). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\nPrior Therapy\n\n* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion\u002Fexclusion criteria.\n\nMyelosuppressive chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 day must have elapsed since the completion of myelosuppressive therapy. However, individuals may receive any of the following medications within 14 days without a \"wash-out period\":\n\n* Hydroxyurea: Hydroxyurea can be initiated and\u002For continued for up to 24 hours prior to the start of protocol therapy.\n* \"Maintenance-style\" therapy: therapy including vincristine (dosed a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed a maximum of one-time weekly), intrathecal therapy (dosed a maximum of one-time weekly) and\u002For dexamethasone (dosed at ≤3 mg\u002Fm2\u002Fdose twice daily) or prednisone (dosed at ≤20 mg\u002Fm2\u002Fdose twice daily) can be continued for up to 24 hours prior to entering the study.\n* Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.\n* Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).\n* Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.\n* Monoclonal antibodies: Maximum of 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody.\n* Immunotherapy: At least 30 days from last infusion of chimeric antigen receptor T cell (CART) therapy or tumor vaccine.\n* Radiation Therapy (XRT):\n\n  1. ≥ 84 days must have passed, from the end of therapy, if patient received prior total body irradiation (TBI).\n  2. ≥ 42 days must have passed, from the end of therapy, if patient received craniospinal irradiation (CSI).\n  3. ≥ 14 days must have passed after whole brain radiotherapy or stereotactic radiation therapy.\n  4. No washout period is required for:\n\n  i. Extramedullary site other than CNS that is a maximum 10 x 10 cm total radiation non-CNS field. If the field is \\> 10 x 10 cm, a 14-day washout period is required. ii. Local ocular radiotherapy as long as subject has measurable\u002Fevaluable disease outside the radiation port.\n* Patients that have received other non-tagraxofusp CD123 targeting agents are eligible. Patients that have previously received tagraxofusp are not eligible.\n\nOrgan Function Requirements\n\nAdequate Bone Marrow Function Defined as:\n\n* Patients should not be known to be refractory to red blood cell or platelet transfusions.\n* Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be ≥20,000\u002Fmm3 to initiate therapy (may receive platelet transfusions).\n\nAdequate Renal Function Defined as:\n\n* Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73m2 OR a normal serum creatinine based on age\u002Fgender in the chart below:\n\nMaximum Serum Creatinine (mg\u002FdL):\n\n* 1 to \\\u003C 2 years old - Male: 0.6, Female: 0.6\n* 2 to \\\u003C 6 years old - Male:0.8, Female: 0.8\n* 6 to \\\u003C 10 years old - Male: 1, Female: 1\n* 10 to \\\u003C 13 years old - Male: 1.2, Female: 1.2\n* 13 to \\\u003C 16 years old - Male: 1.5, Female: 1.4\n* ≥ 16 years old - Male: 1.7, Female: 1.4\n\nThe threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.\n\nAdequate Liver Function Defined as:\n\n* Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x institutional upper limit of normal for age\n* SGPT (ALT) and SGOT (AST) must be less than 3x institutional upper limit of normal.\n* Serum albumin ≥3.2 g\u002FdL (albumin infusion independent).\n\nAdequate Cardiac Function Defined as:\n\n* Shortening fraction of ≥27% by echocardiogram, or\n* Ejection fraction of ≥ 50% by gated radionuclide study\u002Fechocardiogram.\n\nAdequate Pulmonary Function Defined as:\n\n* Pulse oximetry \\> 94% on room air (\\> 90% if at high altitude)\n* No evidence of dyspnea at rest and no exercise intolerance.\n\nReproductive Function\n\n* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.\n* Female patients with infants must agree not to breastfeed their infants while on this study.\n* Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 12 weeks after the last dose of tagraxofusp.\n\nExclusion Criteria\n\nDisease Status:\n\n* Patients with CNS disease are not eligible for Part 1.\n* Patients with isolated CNS disease are not eligible for Part 1 or Part 2.\n* Patients with isolated non-CNS disease are eligible for Part 1 and Part 2.\n\nConcomitant Medications\n\n* Corticosteroids - Patients receiving corticosteroids for disease control who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.\n* Investigational Drugs - Patients who are currently receiving another investigational drug are not eligible. The definition of \"investigational\" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia)\n* Anti-cancer Agents - Patients who are currently receiving or may receive while on therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible \\[with the exceptions being laid out in the inclusion criteria under 'Prior Therapy'\\]. Intrathecal chemotherapy (at the discretion of the primary oncologist) may be given up to one week prior to the initiation of study treatment (day 1 therapy).\n* Anti-GVHD or agents to prevent organ rejection post-transplant - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 4 weeks must have elapsed after the last dose of GVHD meds.\n\nInfection Criteria - Patients are excluded if they have:\n\n* Positive blood culture within 48 hours of study enrollment;\n* Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.\n* A positive fungal culture within 30 days of study enrollment.\n* Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed.\n* Patients will be excluded if they have a known allergy to any of the drugs used in the study.\n* Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.\n* Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.",{"count":78,"type":21},54,[52],"Tagraxofusp is a protein-drug conjugate consisting of a diphtheria toxin redirected to target CD123 has been approved for treatment in pediatric and adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This trial aims to examine the safety of this novel agent in pediatric patients with relapsed\u002Frefractory hematologic malignancies.\n\nThe mechanism by which tagraxofusp kills cells is distinct from that of conventional chemotherapy. Tagraxofusp directly targets CD123 that is present on tumor cells, but is expressed at lower or levels or absent on normal hematopoietic stem cells. Tagraxofusp also utilizes a payload that is not cell cycle dependent, making it effective against both highly proliferative tumor cells and also quiescent tumor cells.\n\nThe rationale for clinical development of tagraxofusp for pediatric patients with hematologic malignancies is based on the ubiquitous and high expression of CD123 on many of these diseases, as well as the highly potent preclinical activity and robust clinical responsiveness in adults observed to date.\n\nThis trial includes two parts: a monotherapy phase and a combination chemotherapy phase. This design will provide further monotherapy safety data and confirm the FDA approved pediatric dose, as well as provide safety data when combined with chemotherapy.\n\nThe goal of this study is to improve survival rates in children and young adults with relapsed hematological malignancies, determine the recommended phase 2 dose (RP2D) of tagraxofusp given alone and in combination with chemotherapy, as well as to describe the toxicities, pharmacokinetics, and pharmacodynamic properties of tagraxofusp in pediatric patients.\n\nAbout 54 children and young adults will participate in this study. Patients with Down syndrome will be included in part 1 of the study.",[82,83,16,84,85,86,87,88,89,90,91],"Hematologic Malignancy","AML","BPDCN","MDS","Lymphoblastic Lymphoma","Lymphoma, B-Cell","Lymphoma, T-Cell","Hodgkin Lymphoma","Mixed Phenotype Acute Leukemia","Acute Undifferentiated Leukemia","2024-12-04",{"date":94,"type":32},"2024-12-06",{"date":96,"type":32},"2022-11-11",{"date":98,"type":21},"2027-11-11",{"name":38,"class":39},31,""]