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.
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
≥ 70 years. Note: Patients ≥ 18 years and < 70 years with active, relapsed or refractory, or high-risk acute leukemia or MDS as defined below.
Karnofsky performance status ≥ 70
Patients who had a prior allogeneic transplant
Patients who have had prior radiotherapy
Patients who have received prior radiopharmaceutical therapy
Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning
City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator