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

Part of paid clinical trials in Duarte, California.

Sponsor
City of Hope Medical Center
Study ID
NCT06287944
Phase
PHASE1
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Actinium Ac 225-DOTA-Daratumumab — BIOLOGICAL
    Given IV
  • Biospecimen Collection — PROCEDURE
    Undergo blood sample collection
  • Bone Marrow Aspiration — PROCEDURE
    Undergo bone marrow biopsy and aspiration
  • Bone Marrow Biopsy — PROCEDURE
    Undergo bone marrow biopsy and aspiration
  • Computed Tomography — PROCEDURE
    Undergo CT
  • Daratumumab — BIOLOGICAL
    Given IV
  • Echocardiography — PROCEDURE
    Undergo echocardiography
  • Fludarabine — DRUG
    Given IV
  • Hematopoietic Cell Transplantation — PROCEDURE
    Undergo SCT
  • Indium In 111-DOTA-Daratumumab — BIOLOGICAL
    Given IV
  • Melphalan — DRUG
    Given IV
  • Multigated Acquisition Scan — PROCEDURE
    Undergo MUGA
  • Radionuclide Imaging — PROCEDURE
    Undergo nuclear scan
  • Single Photon Emission Computed Tomography — PROCEDURE
    Undergo SPECT scan
  • Sirolimus — DRUG
    Given sirolimus
  • Tacrolimus — DRUG
    Given tacrolimus
  • Total Marrow and Lymphoid Irradiation — RADIATION
    Undergo TMLI

Study Details

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.

Key Dates

Start date
Jul 1, 2025
Status verified
May 2026
Primary completion
May 19, 2028
Completion
May 19, 2028

Study Design

Enrollment
15 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment ( Actinium Ac 225-DOTA-Daratumumab)
    Patients receive daratumumab IV over 45 minutes followed by indium In 111-DOTA-daratumumab IV over 15 minutes and actinium Ac 225-DOTA-daratumumab IV over \~20-40 minutes on day -15. Patients receive TMLI BID on days -8 to -5, fludarabine IV on days -4 to -2 and melphalan IV on day -2, followed by HCT on day 0. Patients receive GVHD prophylaxis with sirolimus and tacrolimus starting on day -1. Patients also undergo CT during screening, nuclear scan and SPECT scans on study, bone marrow biopsy and aspiration, echocardiography, or MUGA, and blood sample collection during screening and throughout study.

Primary Outcome Measure

Incidence of adverse events (CTCAE) [ Time Frame: Up to 2 years post-transplant ]

Locations (1)

FacilityCityStateZIPSite coordinators
City of Hope Medical CenterDuarteCalifornia91010
Jeffrey Y. Wong
[email protected]
626-218-2247
Jeffrey Y. Wong (PRINCIPAL_INVESTIGATOR)

Find similar trials in Duarte, CA

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
City of Hope Medical Center· Duarte, CA

Related Studies