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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
Sponsor: City of Hope Medical Center
Summary
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.
Official title: 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
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
15
Start Date
2025-07-01
Completion Date
2028-05-19
Last Updated
2025-07-29
Healthy Volunteers
No
Interventions
Actinium Ac 225-DOTA-Daratumumab
Given IV
Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Computed Tomography
Undergo CT
Daratumumab
Given IV
Echocardiography
Undergo echocardiography
Fludarabine
Given IV
Hematopoietic Cell Transplantation
Undergo SCT
Indium In 111-DOTA-Daratumumab
Given IV
Melphalan
Given IV
Multigated Acquisition Scan
Undergo MUGA
Radionuclide Imaging
Undergo nuclear scan
Single Photon Emission Computed Tomography
Undergo SPECT scan
Sirolimus
Given sirolimus
Tacrolimus
Given tacrolimus
Total Marrow and Lymphoid Irradiation
Undergo TMLI
Locations (1)
City of Hope Medical Center
Duarte, California, United States