Actively Recruiting
Phase I Study of 225Ac-DOTA-Anti-CD38 Daratumumab with Fludarabine, Melphalan, and Total Marrow and Lymphoid Irradiation as Conditioning for Stem Cell Transplant in High-Risk Acute Leukemia and Myelodysplastic Syndrome
Led by City of Hope Medical Center · Updated on 2026-05-18
15
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a new combination treatment for patients with high-risk acute myeloid leukemia AML, acute lymphoblastic leukemia ALL, and myelodysplastic syndrome MDS. This phase I trial studies the safety, side effects, best dose, and potential effectiveness of a radioactive antibody called 225Ac-DOTA-Anti-CD38 daratumumab combined with chemotherapy drugs and targeted radiation as a conditioning treatment before donor stem cell transplant. The treatments aim to prepare the body to accept donor cells and target cancer cells more precisely. Participants receive daratumumab intravenously followed by related radioactive compounds early in the treatment process. They then undergo total marrow and lymphoid irradiation TMLI twice daily for several days, combined with chemotherapy drugs fludarabine and melphalan given intravenously. On day 0, patients receive a stem cell transplant, and preventive medications for graft-versus-host disease GVHD start before transplant. The study includes detailed imaging scans and biopsies before and during treatment to monitor effects. Throughout the trial, participants have regular evaluations including blood tests, bone marrow biopsies, heart and lung function tests, and various scans. After transplant, they are followed closely with frequent visits for the first 100 days, then less often up to two years to track side effects, transplant success, survival, and disease status. Researchers monitor adverse events, transplant-related complications, and overall outcomes to determine the best dose and safety of this new conditioning approach.
CONDITIONS
Brief Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must provide documented informed consent
- Age 60 years or older; patients 18 to under 60 with a comorbidity index of 2 or more are also eligible
- Karnofsky performance status of 70 or higher
- Confirmed diagnosis of acute myeloid leukemia, acute lymphoblastic leukemia, or high-intermediate and high-risk myelodysplastic syndrome as detailed by specific criteria
- Creatinine clearance of 60 ml/minute or higher within 30 days before starting treatment
- Serum bilirubin 2.0 mg/dl or less within 30 days before starting treatment
- Liver enzymes (SGOT and SGPT) 2.5 times the upper limit of normal or less within 30 days before starting treatment
- Ejection fraction of 50% or higher by echocardiogram or MUGA within 30 days before starting treatment
- Lung diffusion capacity (DLCO) and forced expiratory volume (FEV1) greater than 50% predicted within 30 days before starting treatment
- Agreement by males and females of childbearing potential to use effective birth control or abstain from heterosexual activity during and for 6 months after treatment
- Must have an HLA-identical sibling donor or a 10/10 matched unrelated donor willing to donate stem cells
You will not qualify if you...
- Prior allogeneic stem cell transplant
- Prior radiotherapy or radiopharmaceutical therapy
- More than 3 previous remission-inducing treatment regimens for leukemia or MDS
- Receiving other investigational agents or intensive chemotherapy/radiation within 2 weeks before conditioning
- Active uncontrolled infections or illnesses
- History of allergic reactions to similar compounds as study agents
- Other active cancers except non-melanoma skin cancer
- Medical or psychiatric conditions that impair treatment compliance or increase risk
- Pregnant or breastfeeding females
- Inability to comply with study procedures or safety concerns as judged by the investigator
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