nctId: NCT06287944 id: 23694 id: NCI-2024-01131 type: REGISTRY domain: CTRP (Clinical Trial Reporting Program) id: 23694 type: OTHER domain: City of Hope Medical Center 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 overallStatus: NOT_YET_RECRUITING date: 2024-06-18 date: 2027-02-24 date: 2027-02-24 date: 2024-03-01 date: 2024-03-01 name: City of Hope Medical Center class: OTHER name: National Cancer Institute (NCI) 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. conditions: Acute Lymphoblastic Leukemia conditions: Acute Myeloid Leukemia conditions: Myelodysplastic Syndrome studyType: INTERVENTIONAL phases: PHASE1 allocation: NA interventionModel: SINGLE_GROUP primaryPurpose: TREATMENT masking: NONE count: 15 type: ESTIMATED name: Actinium Ac 225-DOTA-Daratumumab name: Biospecimen Collection name: Bone Marrow Aspiration name: Bone Marrow Biopsy name: Computed Tomography name: Daratumumab name: Echocardiography name: Fludarabine name: Hematopoietic Cell Transplantation name: Indium In 111-DOTA-Daratumumab name: Melphalan name: Multigated Acquisition Scan name: Radionuclide Imaging name: Single Photon Emission Computed Tomography name: Sirolimus name: Tacrolimus name: Total Marrow and Lymphoid Irradiation measure: Incidence of adverse events (CTCAE) measure: Incidence of adverse events (Bearman) measure: Dose limiting toxicity (DLT) measure: Maximum tolerated dose/recommended phase II dose (MTD/RP2D) measure: Overall survival (OS) measure: Event-free survival (EFS) measure: Cumulative incidence of relapse/progression (CIR) measure: Graft versus host disease and relapse free survival (GRFS) measure: Complete remission (CR) proportion measure: Non-relapse mortality (NRM) measure: Incidence of infection measure: Neutrophil recovery rate measure: Incidence of grade 2-4 and 3-4 acute graft-versus-host disease (GVHD) measure: Incidence of chronic GVHD (cGVHD) sex: ALL minimumAge: 18 Years stdAges: ADULT stdAges: OLDER_ADULT facility: City of Hope Medical Center city: Duarte state: California zip: 91010 country: United States name: Jeffrey Y. Wong role: CONTACT phone: 626-218-2247 email: jwong@coh.org name: Jeffrey Y. Wong role: PRINCIPAL_INVESTIGATOR lat: 34.13945 lon: -117.97729 hasResults: False