protocolSection identificationModule nctId: NCT06287944, orgStudyIdInfo id: 23694, secondaryIdInfos id: NCI-2024-01131, type: REGISTRY, domain: CTRP (Clinical Trial Reporting Program), secondaryIdInfos id: 23694, type: OTHER, domain: City of Hope Medical Center, secondaryIdInfos id: P30CA033572, type: NIH, link: https://reporter.nih.gov/quickSearch/P30CA033572, briefTitle: 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, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-06-18, primaryCompletionDateStruct date: 2027-02-24, completionDateStruct date: 2027-02-24, studyFirstPostDateStruct date: 2024-03-01, lastUpdatePostDateStruct date: 2024-03-01, sponsorCollaboratorsModule leadSponsor name: City of Hope Medical Center, class: OTHER, collaborators name: National Cancer Institute (NCI), descriptionModule briefSummary: 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/or effective as conditioning treatment for donor stem cell transplant in patients with high-risk AML, ALL, and MDS., conditionsModule conditions: Acute Lymphoblastic Leukemia, conditions: Acute Myeloid Leukemia, conditions: Myelodysplastic Syndrome, designModule studyType: INTERVENTIONAL, phases: PHASE1, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 15, type: ESTIMATED, armsInterventionsModule interventions name: Actinium Ac 225-DOTA-Daratumumab, interventions name: Biospecimen Collection, interventions name: Bone Marrow Aspiration, interventions name: Bone Marrow Biopsy, interventions name: Computed Tomography, interventions name: Daratumumab, interventions name: Echocardiography, interventions name: Fludarabine, interventions name: Hematopoietic Cell Transplantation, interventions name: Indium In 111-DOTA-Daratumumab, interventions name: Melphalan, interventions name: Multigated Acquisition Scan, interventions name: Radionuclide Imaging, interventions name: Single Photon Emission Computed Tomography, interventions name: Sirolimus, interventions name: Tacrolimus, interventions name: Total Marrow and Lymphoid Irradiation, outcomesModule primaryOutcomes measure: Incidence of adverse events (CTCAE), primaryOutcomes measure: Incidence of adverse events (Bearman), primaryOutcomes measure: Dose limiting toxicity (DLT), primaryOutcomes measure: Maximum tolerated dose/recommended phase II dose (MTD/RP2D), secondaryOutcomes measure: Overall survival (OS), secondaryOutcomes measure: Event-free survival (EFS), secondaryOutcomes measure: Cumulative incidence of relapse/progression (CIR), secondaryOutcomes measure: Graft versus host disease and relapse free survival (GRFS), secondaryOutcomes measure: Complete remission (CR) proportion, secondaryOutcomes measure: Non-relapse mortality (NRM), secondaryOutcomes measure: Incidence of infection, secondaryOutcomes measure: Neutrophil recovery rate, secondaryOutcomes measure: Incidence of grade 2-4 and 3-4 acute graft-versus-host disease (GVHD), secondaryOutcomes measure: Incidence of chronic GVHD (cGVHD), eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: City of Hope Medical Center, city: Duarte, state: California, zip: 91010, country: United States, contacts name: Jeffrey Y. Wong, role: CONTACT, phone: 626-218-2247, email: jwong@coh.org, contacts name: Jeffrey Y. Wong, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 34.13945, lon: -117.97729, hasResults: False