A Phase 1/2 interventional study of Daratumumab and Donor Lymphocyte Infusion in Minimal Residual Disease, Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes and Recurrent Adult Acute Myeloid Leukemia, sponsored by Sumithira Vasu. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-21.
Sponsored by Sumithira Vasu · Phase 1/2, Interventional, and Treatment
This phase I/II trial studies the side effects and best dose of donor lymphocyte infusions when given together with daratumumab and to see how well they work in treating participants with acute myeloid leukemia that has come back after a stem cell transplant. A donor lymphocyte infusion is a type of therapy in which lymphocytes (white blood cells) from the blood of a donor are given to a participant who has already received a stem cell transplant from the same donor. The donor lymphocytes may kill remaining cancer cells. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Giving daratumumab and donor white blood cells may work better in treating participants with acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. To evaluate safety and tolerability of daratumumab and escalating doses of donor lymphocyte infusions (DLI) in post-hematopoietic cell transplantation (HCT) patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed to AML (phase I).
II. To evaluate overall response rate to daratumumab and DLI in patients with post-HCT relapsed AML and MDS (phase II).
SECONDARY OBJECTIVES:
I. To assess overall response rates in minimal residual disease (MRD) positive patients and in patients with overt morphological relapse.
II. To assess MRD conversion rates from MRD positive to MRD negative. III. To determine the post-relapse 6-month overall response (OS) rates of patients with relapsed AML and MDS following allogeneic hematopoietic stem cell transplantation (allo-HSCT) who are treated with daratumumab.
IV. To determine the rates of graft-versus-host disease (GVHD) (both grades II-IV and III-IV) and autoimmune side effects of daratumumab.
V. To determine the post-relapse 6-month progression-free survival (PFS) rates of patients with relapsed AML and MDS following allo-HSCT who are treated with daratumumab.
EXPLORATORY OBJECTIVES:
I. To compare CD38 expression levels in myeloid blasts and interferon gamma (IFN-y) levels in plasma at the time of relapse before starting daratumumab and at progression or relapse after daratumumab.
II. To compare peripheral blood T cell number and subsets (CD3, CD4, CD8, (CD38 expression on regulatory T cells [T-regs], CD4 and CD8), T regs, B-regulatory cells, natural killer (NK) cell numbers and bone marrow T cell subsets at the time of relapse before starting daratumumab, at the time of partial/complete response to daratumumab, and at the time of progression or relapse after daratumumab.
III. To evaluate whether daratumumab has (i) direct anti-leukemia effects (ii) antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) and (III) immune modulation of autologous immune system (NK cells, T cells, T-regs, B-regulatory cells [B-regs], and myeloid-derived suppressor cells [MDSCS]) in AML.
IV. To evaluate the effect of daratumumab on exosome content and clearance along with other soluble factors in AML.
V. To evaluate serum interferon (IFN) levels pre-daratumumab, during and post-daratumumab.
VI. To evaluate whether fratricide occurs in patients treated with daratumumab.
OUTLINE: This is a phase I, dose escalation study of donor lymphocyte infusions followed by a phase II study.
Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity. Participants found to be in complete response (CR) at the end of 8 weeks may receive daratumumab IV once every 2 weeks for 8 weeks, and then once monthly for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up for 1 year.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 4 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Sumithira Vasu is the lead sponsor of 6 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Engraftment must have occurred as defined by platelet (PLT) count > 20,000/µL and ANC
Exclusion Criteria:
EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.; seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity.
Biological: Daratumumab · Procedure: Donor Lymphocyte Infusion · Other: Laboratory Biomarker Analysis
Given IV
Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Given via infusion
Also known as: DLI, Donor Leukocyte Infusion
Correlative studies
Safety and Feasibility Defined as the Establishment of the Appropriate Dose Level of Donor Lymphocyte Infusion When Given With a Fixed Dose of Daratumumab
Time frame: Up to 6 months
Rates of Complete Remission
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
Time frame: Up to 6 months
Post-relapse Progression-free Survival
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
Time frame: At 6 months
Post-relapse Overall Survival
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
Time frame: Up to 6 months
Minimal Residual Disease (MRD) Conversion Rates
Time frame: Up to 6 months
Expression of CD38 on Bone Marrow
CD38 expression on bone marrow is checked prior to transplant. Most patients are in remission prior to transplant. Patients who were initially treated at Ohio State University (OSU) will have banked leukemia samples at the time of diagnosis. Expression of CD38 on samples at diagnosis and prior to transplant by immunohistochemical staining will be performed.
Time frame: Up to 6 months
Expression of CD38 in Lymphocytes in Bone Marrow
Percentage of lymphocytes in bone marrow pre- and post-treatment with daratumumab will be studied. In addition to percentage, expression of CD38 on lymphocytes will be evaluated by immunohistochemistry (IHC).
Time frame: Baseline to 6 months
Phenotypic Studies to Evaluate T Cell Exhaustion/Function
This will be performed on bone marrow samples pre-and post-treatment with Daratumumab at the specified time points.
Time frame: Baseline to 6 months
Phenotypic Studies to Evaluate Activation Status of Natural Killer (NK) Cells
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
Time frame: Up to 6 months
T-cell, NK Cell, B-cell, and Myeloid-derived Suppressor Cells (MDSC) Infiltration in Bone Marrow
This will be evaluated on bone marrow samples pre-and post-treatment with daratumumab.
Time frame: Baseline to 6 months
Exosomes From Bone Marrow
This will be examined for both number and also content (protein, messenger ribonucleic acid \[mRNA\], and micro RNAs \[mIRs\]).
Time frame: Up to 6 months
Serial Assessment of Microenvironment
Will be assessed with with stromal cell cultures.
Time frame: Up to 6 months
Chimerism Analysis
Using single-nucleotide polymorphisms, relative contributions from donor vs. recipient in sorted CD3+ and CD33+ cells will be measured and expressed as a percentage.
Time frame: Up to 6 months
Immune Reconstitution
Dr.Gerard Lozanski has developed a panel called the Immunome to study reconstitution of T cells, NK cells and B cells post-transplant. Specific information regarding stages of activation of T cells is also available from this panel.
Time frame: Up to 6 months
Immune Response Post Daratumumab
Time frame: Up to 6 months
Phenotypic Studies to Evaluate T Cell Exhaustion
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
Time frame: Baseline to 6 months
Phenotypic Studies to Evaluate Activation Status of NK Cells
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
Time frame: Baseline to 6 months
Measurements of Cytokines Including But Not Limited to Interferon Gamma (IFN-y)
This will be measured at relapse, pre and post daratumumab treatment. Exosomes from bone marrow will be examined at these serial times for both number and also content (protein, messenger ribonucleic acid \[mRNA\], and micro RNA \[mIRs\]).
Time frame: Up to 6 months
| Milestone | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) |
|---|---|---|
| Started | 2 | 2 |
| Completed | 0 | 0 |
| Not completed | 2 | 2 |
| Withdrew: Disease progression | 2 | 1 |
| Withdrew: Death | 0 | 1 |
No measurements were reported for this outcome.
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
No measurements were reported for this outcome.
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
No measurements were reported for this outcome.
Kaplan-Meier estimates of survival and relapse will be made. Response will be measured using standard criteria. For pre/post-treatment comparisons in the correlative part of the study, a paired t-test will be applied. Two-tailed p values \<0.05 will be considered statistically significant in all analyses.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
CD38 expression on bone marrow is checked prior to transplant. Most patients are in remission prior to transplant. Patients who were initially treated at Ohio State University (OSU) will have banked leukemia samples at the time of diagnosis. Expression of CD38 on samples at diagnosis and prior to transplant by immunohistochemical staining will be performed.
No measurements were reported for this outcome.
Percentage of lymphocytes in bone marrow pre- and post-treatment with daratumumab will be studied. In addition to percentage, expression of CD38 on lymphocytes will be evaluated by immunohistochemistry (IHC).
No measurements were reported for this outcome.
This will be performed on bone marrow samples pre-and post-treatment with Daratumumab at the specified time points.
No measurements were reported for this outcome.
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
No measurements were reported for this outcome.
This will be evaluated on bone marrow samples pre-and post-treatment with daratumumab.
No measurements were reported for this outcome.
This will be examined for both number and also content (protein, messenger ribonucleic acid \[mRNA\], and micro RNAs \[mIRs\]).
No measurements were reported for this outcome.
Will be assessed with with stromal cell cultures.
No measurements were reported for this outcome.
Using single-nucleotide polymorphisms, relative contributions from donor vs. recipient in sorted CD3+ and CD33+ cells will be measured and expressed as a percentage.
No measurements were reported for this outcome.
Dr.Gerard Lozanski has developed a panel called the Immunome to study reconstitution of T cells, NK cells and B cells post-transplant. Specific information regarding stages of activation of T cells is also available from this panel.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
No measurements were reported for this outcome.
This will be performed on bone marrow samples pre-and post-treatment with daratumumab.
No measurements were reported for this outcome.
This will be measured at relapse, pre and post daratumumab treatment. Exosomes from bone marrow will be examined at these serial times for both number and also content (protein, messenger ribonucleic acid \[mRNA\], and micro RNA \[mIRs\]).
No measurements were reported for this outcome.
Collected over Adverse events were collected and monitored from the start of the study until study completion up to an average of 4 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort I (High Risk AML) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | 1/2 (50%) | 0/2 (0%) | 2/2 (100%) |
| Event | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 2/2 | 2/2 |
| BruisingInjury, poisoning and procedural complications | 0/2 | 2/2 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 0/2 | 2/2 |
| FatigueGeneral disorders | 1/2 | 2/2 |
| HyperglycemiaMetabolism and nutrition disorders | 2/2 | 1/2 |
| Infusion related reactionImmune system disorders | 2/2 | 2/2 |
| Lymphocyte count decreasedInvestigations | 2/2 | 2/2 |
| Neutrophil count decreasedInvestigations | 2/2 | 2/2 |
| Platelet count decreasedInvestigations | 2/2 | 2/2 |
| White blood cell decreasedBlood and lymphatic system disorders | 2/2 | 2/2 |
| Age, Continuous(years) | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | Total |
|---|---|---|---|
| Mean | 70 (67 to 73) | 62.5 (58 to 67) | 66.25 (58 to 73) |
| Sex: Female, Male(Participants) | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | Total |
|---|---|---|---|
| Female | 0 | 2 | 2 |
| Male | 2 | 0 | 2 |
| Ethnicity (NIH/OMB)(Participants) | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 2 | 2 | 4 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 2 | 1 | 3 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Region of Enrollment(patients) | Cohort I (High Risk AML) | Cohort 2 (AML/MDS-relapsed After Allo-HSCT) | Total |
|---|---|---|---|
| United States | 2 | 2 | 4 |
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Sumithira Vasu