Minimal Residual DiseasePhase 1/2NCT03537599
Daratumumab and Donor Lymphocyte Infusion in Treating Participants With Relapsed Acute Myeloid Leukemia After Stem Cell Transplant
A Phase 1/2 study testing Daratumumab, Donor Lymphocyte Infusion and Laboratory Biomarker Analysis in people with Minimal Residual Disease and Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, run by Sumithira Vasu at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Minimal Residual Disease, Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Recurrent Adult Acute Myeloid Leukemia
- What is being tested?
- Daratumumab, Donor Lymphocyte Infusion and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2020to 3 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- AML relapse following Allo-HSCT (Morphological relapse, or MRD positive verified by flow cytometry, cytogenetics, and molecular mutations)
- Relapsed/Refractory AML must not be candidates for available therapies known to be effective for treatment of their AML.
- MDS transformed to AML following Allo-HCT
- Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or unrelated donors or atleast a 5/10 haploidentical transplant.
- Engraftment must have occurred as defined by platelet (PLT) count > 20,000/µL and ANC
- 0.5
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- Eastern Cooperative Oncology Group (ECOG) performance status < 3
- Creatinine clearance > 40 ml/min (calculated or measured)
- Aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN), alanine aminotransferase (ALT) < 3 x ULN
- Total bilirubin < 1.5 x ULN
- Off calcineurin inhibitors for at least 2 weeks
- Prednisone dose ≤ 20 mg/day
- Patients with proliferative disease can be cytoreduced with cytotoxic chemotherapy at Investigator discretion, but there should be at least a 14 day window between start of cytoreductive therapy and start of daratumumab
- Blast count ˂20K/day (hydrea use is allowed)
Who cannot join
- No demonstrable evidence of donor chimerism (˂ 55% donor CD3 or CD33 chimerism)
- Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms (MRD status must be verified by surface marker and mutational analyses)
- Active graft-versus-host disease (GvHD) grades II-IV; prior acute GVHD could have occurred but resolved at time of initiation of daratumumab
- Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
- Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI therapy
- Active central nervous system (CNS) disease testicular disease
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- 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).
- Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
- History of grade IV anaphylactic reaction to monoclonal antibody therapy
- Active autoimmune disease prior to transplant
- Concurrent use of any other investigational drugs
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Phase I/II Clinical Trial of Daratumumab and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia Post-Allogeneic Hematopoietic Stem Cell Transplant
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- 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.
- Conditions
- Minimal Residual Disease, Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia
- Being tested
- Daratumumab, Donor Lymphocyte Infusion, Laboratory Biomarker Analysis
- Medical subject headings
- Neoplasm, Residual, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabBiological
Also called Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Given IV
Donor Lymphocyte InfusionProcedure or surgery
Also called DLI, Donor Leukocyte Infusion
Given via infusion
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (DLI, daratumumab) | Experimental | 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. Receives: Biological: Daratumumab; Procedure: Donor Lymphocyte Infusion; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Feasibility Defined as the Establishment of the Appropriate Dose Level of Donor Lymphocyte Infusion When Given With a Fixed Dose of Daratumumab
Measured: Up to 6 months
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: Up to 6 months
Minimal Residual Disease (MRD) Conversion Rates
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start10 Jan 2020
- Primary completion4 Aug 2021
- Study completion3 Feb 2022
Why it stopped: Poor acccrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Minimal Residual DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumithira Vasu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sumithira Vasu, Ohio State University Comprehensive Cancer Center
- Investigators
- Sumithira Vasu, MBBS, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537599
- Sponsor's protocol ID
- OSU-17102
- Other IDs
- NCI-2018-00616
- Status last verified
- May 2025
- First submitted
- 15 May 2018
- Last updated
- 21 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of Daratumumab and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia Post-Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT03537599
- Acronym / sponsor ID
- OSU-17102
- Conditions
- Minimal Residual Disease, Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor acccrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Sumithira VasuUniversity, hospital or other
- Study start
- 10 Jan 2020 (actual)
- Primary completion
- 4 Aug 2021 (actual)
- Study completion
- 3 Feb 2022 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Posted 21 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (DLI, daratumumab) | Experimental | Biological: Daratumumab, Procedure: Donor Lymphocyte Infusion, Other: Laboratory Biomarker AnalysisParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- AML relapse following Allo-HSCT (Morphological relapse, or MRD positive verified by flow cytometry, cytogenetics, and molecular mutations)
- Relapsed/Refractory AML must not be candidates for available therapies known to be effective for treatment of their AML.
- MDS transformed to AML following Allo-HCT
- Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or unrelated donors or atleast a 5/10 haploidentical transplant.
- Engraftment must have occurred as defined by platelet (PLT) count > 20,000/µL and ANC
Key exclusion criteria (11 listed)
- No demonstrable evidence of donor chimerism (˂ 55% donor CD3 or CD33 chimerism)
- Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms (MRD status must be verified by surface marker and mutational analyses)
- Active graft-versus-host disease (GvHD) grades II-IV; prior acute GVHD could have occurred but resolved at time of initiation of daratumumab
- Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
- Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaratumumabAlso: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Given IV | Biological | Treatment (DLI, daratumumab) |
| Donor Lymphocyte InfusionAlso: DLI, Donor Leukocyte InfusionGiven via infusion | Procedure or surgery | Treatment (DLI, daratumumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (DLI, daratumumab) |
Primary outcome
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
4 secondary outcomes
Rates of Complete Remission
Time frame: Up to 6 months
Post-relapse Progression-free Survival
Time frame: At 6 months
Post-relapse Overall Survival
Time frame: Up to 6 months
Minimal Residual Disease (MRD) Conversion Rates
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sumithira Vasu, MBBS principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Daratumumab, Donor Lymphocyte Infusion and Laboratory Biomarker Analysis in people with Minimal Residual Disease and Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes, run by Sumithira Vasu at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.