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
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.
Description
PRIMARY OBJECTIVES: I. Describe toxicities attributable to actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-anti-CD38 daratumumab) radioimmunotherapy by dose level in patients treated under this regimen. II. Determine the maximum tolerated dose/recommended phase II dose (MTD/RP2D) of 225Ac-DOTA-anti-CD38 daratumumab radioimmunotherapy with fixed doses of organ sparing TMLI (12 Gy), fludarabine and melphalan (FM100) as conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) for treatment of high-risk acute myeloid leukemias, acute lymphoblastic leukemia or myelodysplastic syn…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Assent, when appropriate, will be obtained per institutional guidelines * ≥ 60 years. Note: Patients ≥ 18 years and \< 60 years with HCT-comorbidity index (CI) ≥ 2 are also included * Karnofsky performance status ≥ 70 * Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories : * Acute myelogenous leukemia: * Patients with de novo or secondary disease in unfavorable risk group including poor risk cyto…
Interventions
- BiologicalActinium Ac 225-DOTA-Daratumumab
Given IV
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow biopsy and aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
- ProcedureComputed Tomography
Undergo CT
- BiologicalDaratumumab
Given IV
- ProcedureEchocardiography
Location
- City of Hope Medical CenterDuarte, California