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

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.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

BIOLOGICAL

Actinium Ac 225-DOTA-Daratumumab

Given IV

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

PROCEDURE

Computed Tomography

Undergo CT

BIOLOGICAL

Daratumumab

Given IV

PROCEDURE

Echocardiography

Undergo echocardiography

DRUG

Fludarabine

Given IV

PROCEDURE

Hematopoietic Cell Transplantation

Undergo SCT

BIOLOGICAL

Indium In 111-DOTA-Daratumumab

Given IV

DRUG

Melphalan

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

PROCEDURE

Radionuclide Imaging

Undergo nuclear scan

PROCEDURE

Single Photon Emission Computed Tomography

Undergo SPECT scan

DRUG

Sirolimus

Given sirolimus

DRUG

Tacrolimus

Given tacrolimus

RADIATION

Total Marrow and Lymphoid Irradiation

Undergo TMLI

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Jeffrey Y Wong · City of Hope Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-01

Primary Completion

2028-05-19

Completion

2028-05-19

FDA Drug

Yes

Countries

• United States

Study Locations