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
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 16 days from day -15 to day 0
Participants receive intravenous daratumumab, indium In 111-DOTA-daratumumab, and actinium Ac 225-DOTA-daratumumab on day -15, followed by total marrow and lymphoid irradiation twice daily from days -8 to -5, fludarabine intravenously from days -4 to -2, melphalan intravenously on day -2, then undergo hematopoietic cell transplantation on day 0. Participants start graft-versus-host disease prophylaxis with sirolimus and tacrolimus on day -1.
Multiple visits including day -15, days -8 to -5, days -4 to -2, day -2, day -1, and day 0
Duration - Up to 2 years post-transplant
Participants are followed up for safety monitoring including adverse events, engraftment, graft-versus-host disease, infections, and survival outcomes. Follow-up visits occur twice weekly for the first 100 days post-transplant, then twice monthly up to 6 months post-transplant, followed by monthly visits until immunosuppressive therapy is discontinued without evidence of graft-versus-host disease, and then at least yearly for up to 2 years.
Twice weekly visits for first 100 days, twice monthly visits up to 6 months, monthly visits thereafter, and yearly visits up to 2 years
Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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