[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100538216":3},{"organization":4,"armGroups":7,"interventions":30,"overallOfficials":206,"centralContacts":52,"locations":210,"responsibleParty":231,"collaborators":233,"id":237,"slug":238,"hasResults":239,"nctId":240,"briefTitle":241,"officialTitle":242,"acronym":52,"eligibilityCriteria":243,"healthyVolunteers":239,"sex":244,"minAge":245,"maxAge":246,"enrollmentInfo":247,"targetDuration":52,"studyType":250,"phases":251,"briefSummary":253,"conditions":254,"keywords":52,"overallStatus":212,"whyStopped":52,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":259,"startDateStruct":262,"completionDateStruct":264,"leadSponsor":266,"locationsCount":267},{"fullName":5,"class":6},"City of Hope Medical Center","OTHER",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"Treatment ( Actinium Ac 225-DOTA-Daratumumab)","EXPERIMENTAL","Patients receive daratumumab IV over 45 minutes followed by indium In 111-DOTA-daratumumab IV over 15 minutes and actinium Ac 225-DOTA-daratumumab IV over \\~20-40 minutes on day -15. Patients receive TMLI BID on days -8 to -5, fludarabine IV on days -4 to -2 and melphalan IV on day -2, followed by HCT on day 0. Patients receive GVHD prophylaxis with sirolimus and tacrolimus starting on day -1. Patients also undergo CT during screening, nuclear scan and SPECT scans on study, bone marrow biopsy and aspiration, echocardiography, or MUGA, and blood sample collection during screening and throughout study.",[13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29],"Biological: Actinium Ac 225-DOTA-Daratumumab","Procedure: Biospecimen Collection","Procedure: Bone Marrow Aspiration","Procedure: Bone Marrow Biopsy","Procedure: Computed Tomography","Biological: Daratumumab","Procedure: Echocardiography","Drug: Fludarabine","Procedure: Hematopoietic Cell Transplantation","Biological: Indium In 111-DOTA-Daratumumab","Drug: Melphalan","Procedure: Multigated Acquisition Scan","Procedure: Radionuclide Imaging","Procedure: Single Photon Emission Computed Tomography","Drug: Sirolimus","Drug: Tacrolimus","Radiation: Total Marrow and Lymphoid Irradiation",[31,39,48,53,59,73,83,89,95,108,114,131,148,160,176,187,199],{"type":32,"name":33,"description":34,"armGroupLabels":35,"otherNames":36},"BIOLOGICAL","Actinium Ac 225-DOTA-Daratumumab","Given IV",[9],[37,38],"225Ac-DOTA-Daratumumab","[225Ac]-DOTA-Daratumumab",{"type":40,"name":41,"description":42,"armGroupLabels":43,"otherNames":44},"PROCEDURE","Biospecimen Collection","Undergo blood sample collection",[9],[45,46,47],"Biological Sample Collection","Biospecimen Collected","Specimen Collection",{"type":40,"name":49,"description":50,"armGroupLabels":51,"otherNames":52},"Bone Marrow Aspiration","Undergo bone marrow biopsy and aspiration",[9],null,{"type":40,"name":54,"description":50,"armGroupLabels":55,"otherNames":56},"Bone Marrow Biopsy",[9],[57,58],"Biopsy of Bone Marrow","Biopsy, Bone Marrow",{"type":40,"name":60,"description":61,"armGroupLabels":62,"otherNames":63},"Computed Tomography","Undergo CT",[9],[64,65,66,67,68,69,70,71,72],"CAT","CAT Scan","Computed Axial Tomography","Computerized Axial Tomography","Computerized axial tomography (procedure)","Computerized Tomography","CT","CT Scan","tomography",{"type":32,"name":74,"description":34,"armGroupLabels":75,"otherNames":76},"Daratumumab",[9],[77,78,79,80,81,82],"Daratumumab Biosimilar HLX15","Daratumumab-fihj","Darzalex","HLX15","HuMax-CD38","JNJ-54767414",{"type":40,"name":84,"description":85,"armGroupLabels":86,"otherNames":87},"Echocardiography","Undergo echocardiography",[9],[88],"EC",{"type":90,"name":91,"description":34,"armGroupLabels":92,"otherNames":93},"DRUG","Fludarabine",[9],[94],"Fluradosa",{"type":40,"name":96,"description":97,"armGroupLabels":98,"otherNames":99},"Hematopoietic Cell Transplantation","Undergo SCT",[9],[100,101,102,103,104,105,106,107],"HCT","Hematopoietic Stem Cell Infusion","Hematopoietic Stem Cell Transplantation","HSCT","SCT","Stem Cell Transplant","stem cell transplantation","Stem Cell Transplantation, NOS",{"type":32,"name":109,"description":34,"armGroupLabels":110,"otherNames":111},"Indium In 111-DOTA-Daratumumab",[9],[112,113],"111In-DOTA-Daratumumab","[111In]-DOTA-Daratumumab",{"type":90,"name":115,"description":34,"armGroupLabels":116,"otherNames":117},"Melphalan",[9],[118,119,120,121,122,123,124,125,126,127,128,129,130],"Alanine Nitrogen Mustard","CB-3025","L-PAM","L-Phenylalanine Mustard","L-Sarcolysin","L-Sarcolysin Phenylalanine mustard","L-Sarcolysine","Melphalanum","Phenylalanine Mustard","Phenylalanine Nitrogen Mustard","Sarcoclorin","Sarkolysin","WR-19813",{"type":40,"name":132,"description":133,"armGroupLabels":134,"otherNames":135},"Multigated Acquisition Scan","Undergo MUGA",[9],[136,137,138,139,140,141,142,143,144,145,146,147],"Blood Pool Scan","Equilibrium Radionuclide Angiography","Gated Blood Pool Imaging","Gated Heart Pool Scan","MUGA","MUGA Scan","Multi-Gated Acquisition Scan","Radionuclide Ventriculogram Scan","Radionuclide Ventriculography","RNVG","SYMA Scanning","Synchronized Multigated Acquisition Scanning",{"type":40,"name":149,"description":150,"armGroupLabels":151,"otherNames":152},"Radionuclide Imaging","Undergo nuclear scan",[9],[153,154,155,156,157,158,159],"NM","Nuclear Medicine","nuclear medicine scan","radioimaging","Radionuclide Scanning","Scan","Scintigraphy",{"type":40,"name":161,"description":162,"armGroupLabels":163,"otherNames":164},"Single Photon Emission Computed Tomography","Undergo SPECT scan",[9],[165,166,167,168,169,170,171,172,173,174,175],"Medical Imaging, Single Photon Emission Computed Tomography","Single Photon Emission Tomography","Single-Photon Emission Computed","single-photon emission computed tomography","SPECT","SPECT imaging","SPECT SCAN","SPET","ST","tomography, emission computed, single photon","Tomography, Emission-Computed, Single-Photon",{"type":90,"name":177,"description":178,"armGroupLabels":179,"otherNames":180},"Sirolimus","Given sirolimus",[9],[181,182,183,184,185,186],"AY 22989","RAPA","Rapamune","Rapamycin","SILA 9268A","WY-090217",{"type":90,"name":188,"description":189,"armGroupLabels":190,"otherNames":191},"Tacrolimus","Given tacrolimus",[9],[192,193,194,195,196,197,198],"FK 506","FK-506","Fujimycin","Hecoria","Prograf","Protopic","Tacforius",{"type":200,"name":201,"description":202,"armGroupLabels":203,"otherNames":204},"RADIATION","Total Marrow and Lymphoid Irradiation","Undergo TMLI",[9],[205],"TMLI",[207],{"name":208,"affiliation":5,"role":209},"Jeffrey Y Wong","PRINCIPAL_INVESTIGATOR",[211],{"facility":5,"status":212,"city":213,"state":214,"zip":215,"country":216,"countryCode":217,"cosmosGeoPoint":218,"geoPoint":223,"contacts":224},"RECRUITING","Duarte","California","91010","United States","US",{"type":219,"coordinates":220},"Point",[221,222],-117.97729,34.13945,{"lat":222,"lon":221},[225,230],{"name":226,"role":227,"phone":228,"phoneExt":52,"email":229},"Jeffrey Y. Wong","CONTACT","626-218-2247","jwong@coh.org",{"name":226,"role":209,"phone":52,"phoneExt":52,"email":52},{"type":232,"investigatorFullName":52,"investigatorTitle":52,"investigatorAffiliation":52,"oldNameTitle":52,"oldOrganization":52},"SPONSOR",[234],{"name":235,"class":236},"National Cancer Institute (NCI)","NIH","100538216","phase-1-225ac-dota-anti-cd38-daratumumab-monoclonal-antibody-with-fludarabine-melphalan-and-total-marrow-and-lymphoid-irradiation-as-conditioning-treatment-for-donor-stem-cell-transplant-in-patients-with-high-risk-acute-myeloid-leukemia-acute-lymphoblastic-leukemia-and-myelodysplastic-syndrome-100538216",false,"NCT06287944","225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome","Phase I Study of Escalating Doses of 225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody Added to the Conditioning Regimen of Fludarabine, Melphalan and Organ Sparing Total Marrow and Lymphoid Irradiation (TMLI) as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* ≥ 70 years. Note: Patients ≥ 18 years and \\\u003C 70 years with active, relapsed or refractory, or high-risk acute leukemia or MDS as defined below.\n* Karnofsky performance status ≥ 70\n* Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories :\n\n  * Acute myelogenous leukemia:\n\n    * Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5,5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease, OR\n    * Patients with a complete morphological remission (CR) with minimal residual disease (MRD)-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetic after at least 2 prior induction therapies, OR\n    * Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment\n  * Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories per Revised International Prognostic Scoring System- (IPSS-R)\n  * Acute lymphocytic leukemia\n* Evidence of CD38 expression by flow cytometry AND one of the below\n\n  * Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (\\\u003C 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p, OR\n  * Patients with a complete response (CR) with MRD-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetics after at least 2 prior induction therapies, OR\n  * Patients with chemosensitive active disease defined as at least 25% reduction in their blast count after last treatment\n  * Patients with myelofibrosis (primary or secondary, including post-polycythemia vera and post-essential thrombocythemia myelofibrosis) may be eligible for enrollment if they meet criteria for high-risk disease and are planned for allogeneic hematopoietic cell transplantation.\n* Eligible patients include those with:\n\n  * Accelerated-phase or blast-phase myelofibrosis, defined as 10% to 19% blasts or ≥20% blasts, respectively, in peripheral blood or bone marrow\n  * High-risk chronic-phase primary or secondary myelofibrosis, defined as disease meeting transplant-appropriate risk criteria by a validated MF prognostic model, including DIPSS intermediate-2 or high-risk; DIPSS-plus intermediate-2 or high-risk; MIPSS70 intermediate, high, or very high-risk; MIPSS70-plus or MIPSS70-plus version 2.0 intermediate, high, or very high-risk; GIPSS intermediate-2 or high-risk; or MYSEC-PM intermediate-2 or high-risk for post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Patients may also qualify based on adverse clinical, cytogenetic, or molecular features supporting high-risk disease biology and transplant candidacy, including complex karyotype, monosomal karyotype, very high-risk karyotype, high molecular risk mutations, transfusion-dependent anemia, thrombocytopenia, circulating blasts, constitutional symptoms, or symptomatic splenomegaly despite standard therapy\n  * Suboptimal response, progression, or intolerance to prior JAK inhibitor therapy, defined as failure to achieve adequate spleen or symptom response after an appropriate trial of therapy, generally at least 12 weeks at an appropriate or maximally tolerated dose when clinically feasible; loss of prior spleen or symptom response; worsening splenomegaly; persistent or worsening constitutional symptoms attributable to MF; worsening cytopenias or transfusion dependence; progression to accelerated-phase or blast-phase disease; emergence of adverse cytogenetic or molecular features; or inability to continue JAK inhibitor therapy due to treatment-related toxicity. A minimum duration of JAK inhibitor exposure is not required when the treating investigator determines that continued therapy is not clinically appropriate due to rapidly progressive disease, accelerated-phase or blast-phase transformation, clinically significant cytopenias, intolerance, or urgent need to proceed to allogeneic HCT. The rationale for early determination of JAK inhibitor failure or inability to continue JAK inhibitor therapy will be documented in the medical record.\n  * Persistent disease burden, including persistent splenomegaly, circulating or marrow blasts, transfusion dependence, cytopenias attributable to MF, leukocytosis, thrombocytopenia, adverse cytogenetic or molecular features, extramedullary hematopoiesis, or progression despite standard therapy, may support high-risk classification but does not constitute a separate eligibility criterion unless the patient also meets the defined advanced-phase, validated risk-model, or JAK inhibitor failure criteria above.\n\n    \\*\\*See Appendix F: Defined Risk Scoring Systems in MF\n  * All patients must demonstrate CD38 expression on disease-relevant cell populations (bone marrow and\u002For peripheral blood) as assessed by flow cytometry or an equivalent validated assay prior to enrollment.\n\nClinical Laboratory and Organ Function Criteria (To be performed within 30 days prior to Day 1 of protocol therapy unless otherwise stated) or (acceptable windows for tests are indicated in the Study Calendar Section 10.0).\n\n* A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml\u002Fminute (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Patients must have a serum bilirubin ≤ 2.0 mg\u002Fdl (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Patients must have a serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Patients must have a serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) ≥ 50% (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Diffusion capacity of the lung for carbon monoxide (DLCO) \\> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Forced expiratory volume in 1 second (FEV1) \\> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n* DONOR SPECIFIC CRITERIA: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate mobilized peripheral blood stem cells (preferred) or bone marrow, or have a 10\u002F10 (A, B, C, DR and DQ) allele matched unrelated donor. DQ or DP mismatch is allowed per discretion of the principal investigator. City of Hope (COH) standards of practice (SOP) (B.001.11) will be used for allogeneic donor evaluation, selection, and consent. Donor screening will be in compliance with all requirements of Food and Drug Administration (FDA) regulation 21 CFR Part 1271 including donor screening for COVID-19 exposure or infection\n\nExclusion Criteria:\n\n* Patients who had a prior allogeneic transplant\n* Patients who have had prior radiotherapy\n* Patients who have received prior radiopharmaceutical therapy\n* Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning\n* Patients should have discontinued all previous intensive therapy, chemotherapy, or radiotherapy for 2 weeks prior to commencing therapy on this study. Note: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent\n* Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers\n* Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection\n* The recipient has a medical problem or neurologic\u002Fpsychiatric dysfunction which would impair his\u002Fher ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the investigator (treating physician) would place the recipient at unacceptable risk\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)","ALL","18 Years","70 Years",{"count":248,"type":249},15,"ESTIMATED","INTERVENTIONAL",[252],"PHASE1","This phase I trial tests the safety, side effects, best dose, and effectiveness of 225Ac-DOTA-Anti-CD38 daratumumab monoclonal antibody in combination with fludarabine, melphalan and total marrow and lymphoid irradiation (TMLI) as conditioning treatment for donor stem cell transplant in patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Radioimmunotherapy is treatment with a radioactive substance that is linked to a monoclonal antibody, such as daratumumab, that will find and attach to cancer cells. Radiation given off by the radioisotope my help kill the cancer cells. Chemotherapy drugs, such as fludarabine and melphalan, 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. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TMLI is a targeted form of body radiation that targets marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize therapy effect. Actinium Ac 225-DOTA-daratumumab combined with fludarabine, melphalan and TMLI may be safe, tolerable, and\u002For effective as conditioning treatment for donor stem cell transplant in patients with high-risk AML, ALL, and MDS.",[255,256,257],"Acute Lymphoblastic Leukemia","Acute Myeloid Leukemia","Myelodysplastic Syndrome","2026-07-30",{"date":260,"type":261},"2026-07-31","ACTUAL",{"date":263,"type":261},"2025-07-01",{"date":265,"type":249},"2028-05-19",{"name":5,"class":6},1]