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OncoMatch/Clinical Trials/NCT06287944

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

Is NCT06287944 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments for acute lymphoblastic leukemia.

Phase 1RecruitingCity of Hope Medical CenterNCT06287944Data as of May 2026

Treatment: Actinium Ac 225-DOTA-Daratumumab · Daratumumab · Fludarabine · Indium In 111-DOTA-Daratumumab · Melphalan · Sirolimus · TacrolimusThis 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.

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Extracted eligibility criteria

Cancer type

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Myelodysplastic Syndrome

Biomarker criteria

Required: MLL rearrangement

t(v;11q23): MLL rearranged

Required: BCR t(9;22)

t(9;22) (q34;q11.2)

Required: IKZF1 iAMP21

iAMP21

Required: TP53 abnormal 17p

abnormal 17p

Excluded: FLT3 FLT3-NPM1+

intermediate risk groups accept patients with FLT3-NPM1+ disease [excluded]

Prior therapy

Max 3 prior lines

Cannot have received: allogeneic transplant

Patients who had a prior allogeneic transplant

Cannot have received: radiation therapy to the lung, liver, and kidney

All patients with prior radiation treatment to the lung, liver, and kidney

Cannot have received: radiopharmaceutical therapy

Patients who have received prior radiopharmaceutical therapy

Lab requirements

Kidney function

creatinine clearance ≥ 60 ml/min

Liver function

serum bilirubin ≤ 2.0 mg/dl; SGOT ≤ 2.5x ULN; SGPT ≤ 2.5x ULN

Cardiac function

ejection fraction ≥ 50% by echocardiogram or MUGA

creatinine clearance ≥ 60 ml/min; serum bilirubin ≤ 2.0 mg/dl; SGOT ≤ 2.5x ULN; SGPT ≤ 2.5x ULN; ejection fraction ≥ 50%; DLCO > 50% predicted; FEV1 > 50% predicted

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • City of Hope Medical Center · Duarte, California

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