225Ac-DOTA-Anti-CD38 Daratumumab for High-Risk Leukemia and Myelodysplastic Syndrome
This study is testing a new treatment for high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). It combines a drug called 225Ac-DOTA-Anti-CD38 daratumumab with chemotherapy (fludarabine and melphalan) and radiation (total marrow and lymphoid irradiation) before a donor stem cell transplant. Daratumumab is a monoclonal antibody, which means it's a type of immune therapy that targets a protein called CD38 on cancer cells to help your immune system fight them. This Phase 1 study aims to find the safest and most effective dose of 225Ac-DOTA-Anti-CD38 daratumumab and understand its side effects. You might be eligible if you are 60 or older, or 18-59 with certain health conditions. The study plans to enroll 15 participants, but its current status is unclear.
- Study design
- This is a Phase 1 interventional study designed to test the safety and best dose of the treatment. It plans to enroll 15 participants.
- What's involved
- You would undergo blood sample collection, bone marrow biopsy and aspiration, and CT scans. The duration of these commitments is not specified.
- Compensation
- Not stated in the trial record.
- Follow-up
- You would be followed for adverse events for up to 2 years after the stem cell transplant.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
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
Recruiting
PHASE1Ages 18–70InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~15 participants
Updated 2026-07-31 on ClinicalTrials.gov
What's tested:Actinium Ac 225-DOTA-DaratumumabBiospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyDaratumumab
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events (CTCAE)
Measured over Up to 2 years post-transplant
+3 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Jeffrey Y Wong · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
≥ 70 years. Note: Patients ≥ 18 years and \< 70 years with active, relapsed or refractory, or high-risk acute leukemia or MDS as defined below.
Karnofsky performance status ≥ 70
Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories :
Acute myelogenous leukemia:
Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5,5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease, OR
Patients with a complete morphological remission (CR) with minimal residual disease (MRD)-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetic after at least 2 prior induction therapies, OR
Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment
Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories per Revised International Prognostic Scoring System- (IPSS-R)
Acute lymphocytic leukemia
Evidence of CD38 expression by flow cytometry AND one of the below
Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (\< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p, OR
Patients with a complete response (CR) with MRD-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetics after at least 2 prior induction therapies, OR
Patients with chemosensitive active disease defined as at least 25% reduction in their blast count after last treatment
Patients with myelofibrosis (primary or secondary, including post-polycythemia vera and post-essential thrombocythemia myelofibrosis) may be eligible for enrollment if they meet criteria for high-risk disease and are planned for allogeneic hematopoietic cell transplantation.
Eligible patients include those with:
Accelerated-phase or blast-phase myelofibrosis, defined as 10% to 19% blasts or ≥20% blasts, respectively, in peripheral blood or bone marrow
High-risk chronic-phase primary or secondary myelofibrosis, defined as disease meeting transplant-appropriate risk criteria by a validated MF prognostic model, including DIPSS intermediate-2 or high-risk; DIPSS-plus intermediate-2 or high-risk; MIPSS70 intermediate, high, or very high-risk; MIPSS70-plus or MIPSS70-plus version 2.0 intermediate, high, or very high-risk; GIPSS intermediate-2 or high-risk; or MYSEC-PM intermediate-2 or high-risk for post-polycythemia vera or post-essential thrombocythemia myelofibrosis. Patients may also qualify based on adverse clinical, cytogenetic, or molecular features supporting high-risk disease biology and transplant candidacy, including complex karyotype, monosomal karyotype, very high-risk karyotype, high molecular risk mutations, transfusion-dependent anemia, thrombocytopenia, circulating blasts, constitutional symptoms, or symptomatic splenomegaly despite standard therapy
Suboptimal response, progression, or intolerance to prior JAK inhibitor therapy, defined as failure to achieve adequate spleen or symptom response after an appropriate trial of therapy, generally at least 12 weeks at an appropriate or maximally tolerated dose when clinically feasible; loss of prior spleen or symptom response; worsening splenomegaly; persistent or worsening constitutional symptoms attributable to MF; worsening cytopenias or transfusion dependence; progression to accelerated-phase or blast-phase disease; emergence of adverse cytogenetic or molecular features; or inability to continue JAK inhibitor therapy due to treatment-related toxicity. A minimum duration of JAK inhibitor exposure is not required when the treating investigator determines that continued therapy is not clinically appropriate due to rapidly progressive disease, accelerated-phase or blast-phase transformation, clinically significant cytopenias, intolerance, or urgent need to proceed to allogeneic HCT. The rationale for early determination of JAK inhibitor failure or inability to continue JAK inhibitor therapy will be documented in the medical record.
Persistent disease burden, including persistent splenomegaly, circulating or marrow blasts, transfusion dependence, cytopenias attributable to MF, leukocytosis, thrombocytopenia, adverse cytogenetic or molecular features, extramedullary hematopoiesis, or progression despite standard therapy, may support high-risk classification but does not constitute a separate eligibility criterion unless the patient also meets the defined advanced-phase, validated risk-model, or JAK inhibitor failure criteria above.
All patients must demonstrate CD38 expression on disease-relevant cell populations (bone marrow and/or peripheral blood) as assessed by flow cytometry or an equivalent validated assay prior to enrollment.
A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml/minute (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Patients must have a serum bilirubin ≤ 2.0 mg/dl (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Patients must have a serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Patients must have a serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) ≥ 50% (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Diffusion capacity of the lung for carbon monoxide (DLCO) \> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Forced expiratory volume in 1 second (FEV1) \> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
DONOR SPECIFIC CRITERIA: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate mobilized peripheral blood stem cells (preferred) or bone marrow, or have a 10/10 (A, B, C, DR and DQ) allele matched unrelated donor. DQ or DP mismatch is allowed per discretion of the principal investigator. City of Hope (COH) standards of practice (SOP) (B.001.11) will be used for allogeneic donor evaluation, selection, and consent. Donor screening will be in compliance with all requirements of Food and Drug Administration (FDA) regulation 21 CFR Part 1271 including donor screening for COVID-19 exposure or infection
Exclusion
Patients who had a prior allogeneic transplant
Patients who have had prior radiotherapy
Patients who have received prior radiopharmaceutical therapy
Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning
Patients should have discontinued all previous intensive therapy, chemotherapy, or radiotherapy for 2 weeks prior to commencing therapy on this study. Note: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers
Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the investigator (treating physician) would place the recipient at unacceptable risk
Females only: Pregnant or breastfeeding
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
What this trial measures
- Incidence of adverse events (CTCAE)Up to 2 years post-transplant
Toxicity will be scored on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 scale. Toxicity will be recorded in each patient and will include the type, severity, and probable association with the study regimen.
- Incidence of adverse events (Bearman)Up to 2 years post-transplant
Toxicity will be scored on the Bearman Scale. Toxicity will be recorded in each patient and will include the type, severity, and probable association with the study regimen.
- Dose limiting toxicity (DLT)Up to 30 days post-stem cell infusion
DLT will be graded using the NCI CTCAE v5 scale.
- Maximum tolerated dose/recommended phase II dose (MTD/RP2D)Up to 30 days post stem cell infusion
MTD/RP2D will be defined as the highest dose where 6 patients have been treated and at most on patient experiences a DLT.