Venetoclax or Placebo in Combination With Reduced-Intensity Conditioning Hematopoietic Cell (Bone Marrow/Blood Stem Cell) Transplant and as Maintenance Therapy After Transplant in Patients With Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
A Two Cohort, Randomized, Double-Blind, Placebo-Controlled, Phase II Multi-Center Signal-Finding Study of Venetoclax Combined With Reduced-Intensity Conditioning Followed by Allogeneic Hematopoietic Cell Transplantation Then Venetoclax Maintenance in Adult Patients With Acute Myeloid Leukemia in First Complete Remission: A MyeloMATCH Sub-Study
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interventional
244
0 countries
N/A
Brief Summary
This phase II MyeloMATCH treatment trial compares the effect of adding venetoclax or placebo to reduced intensity conditioning chemotherapy with fludarabine and busulfan or melphalan, with or without total body irradiation, followed by hematopoietic stem cell transplant and either venetoclax or placebo maintenance therapy after transplant, for the treatment of patients with acute myeloid leukemia (AML). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving chemotherapy and total body irradiation before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Adding venetoclax to conditioning therapy before, and giving it as maintenance therapy after, a hematopoietic stem cell transplant may be a more effective treatment option than the usual approach in patients with AML.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2026
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 1, 2025
CompletedFirst Posted
Study publicly available on registry
May 2, 2025
CompletedStudy Start
First participant enrolled
July 17, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
May 15, 2028
Study Completion
Last participant's last visit for all outcomes
May 15, 2028
May 13, 2026
February 1, 2026
1.8 years
May 1, 2025
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Event free survival (EFS)
MRD positivity is defined as \>= 0.1% leukemic blasts by MyeloMatch flow cytometry. Day 100 is defined as 100 days (day +100 +/- 10 days) after hematopoietic cell infusion (day 0). The day 100 EFS rates will be compared between venetoclax versus placebo arms using a using a two-sided log-rank test.
From randomization to minimal residual disease (MRD) persistence, MRD relapse, morphologic relapse, or death from any cause, assessed up to day +100
Secondary Outcomes (11)
MRD conversion rate
At day +30
EFS
From the time of randomization to relapse or death, assessed at 12 months
Overall survival
From randomization to death from any cause, assessed up to 10 years
Relapse free survival
From randomization or re-randomization to morphologic relapse or death from any cause, assessed up to 10 years
Non relapse mortality
From randomization to death from any cause other than morphologic relapse, assessed up to 10 years
- +6 more secondary outcomes
Study Arms (6)
Conditioning 1A (matched donors with venetoclax)
EXPERIMENTALPatients receive venetoclax PO QD on days -10 to -2, fludarabine IV on days -6 or -5 to -2 and busulfan IV on days -3 to -2 or BID on days -5 to -2 or melphalan IV on day -2. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Conditioning 1B (matched donor with placebo)
PLACEBO COMPARATORPatients receive placebo PO QD on days -10 to -2, fludarabine IV on days -6 or -5 to -2 and busulfan IV on days -3 to -2 or BID on days -5 to -2 or melphalan IV on day -2. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Conditioning 2A (haplo/mismatched donor with venetoclax)
EXPERIMENTALPatients receive venetoclax PO QD on days -10 to -2, melphalan IV on day -6, fludarabine IV on days -5 to -2 and undergo total body irradiation once on day -1. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Conditioning 2B (haplo/mismatched unrelated and placebo)
PLACEBO COMPARATORPatients receive placebo PO QD on days -10 to -2, melphalan IV on day -6, fludarabine IV on days -5 to -2 and undergo total body irradiation once on day -1. Patients then receive hematopoietic cell transplant IV on day 0. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray, echocardiography or MUGA during screening, and bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Maintenance I (venetoclax)
EXPERIMENTALPatients receive venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year post transplant (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Maintenance II (placebo)
PLACEBO COMPARATORPatients receive placebo PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year post transplant (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy and blood, urine and buccal swab collection throughout the study. Patients may also undergo PET scan and/or CT scan throughout the study.
Interventions
Undergo echocardiography
Given IV
Given IV
Given PO
Undergo total body irradiation
Given PO
Undergo MUGA
Undergo blood, urine and buccal swab collection
Undergo bone marrow biopsy
Given IV
Given IV
Undergo CT scan
Undergo PET scan
Undergo chest x-ray
Eligibility Criteria
You may qualify if:
- Patients must be registered to the Master Screening and Reassessment Protocol (MSRP) and assigned to this protocol by the MATCHBox Treatment Verification Team
- STEP 1: History of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria in first complete remission with morphologic complete remission (CR) or CR with incomplete hematologic recovery (CRi) defined as less than 5% bone marrow blasts by morphology with no circulating leukemic myeloblasts and no known extramedullary disease
- STEP 1: MRD status by MDNet must have been performed
- STEP 1 COHORT 1: Human leukocyte antigen (HLA)-matched donor defined as one of the following:
- Sibling donor must be a 6/6 match at HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using deoxyribonucleic acid \[DNA\]-based typing)
- Related donor other than sibling must be an 8/8 match for HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing
- Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing
- Age 40-75 years
- STEP 1 COHORT 1: Not recommended for a myeloablative regimen by treating investigator
- STEP 1 COHORT 2: Haploidentical or HLA-mismatched unrelated donor defined as one of the following:
- Haploidentical donors: Related donor must be a haploidentical 3/6, 4/6, or 5/6 match at HLA-A and -B (intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing)
- HLA-mismatched unrelated donors: Unrelated donor must be a 6/8 or 7/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing, ideally age \< 35
- Age 18-75 years
- STEP 1 COHORT 2: Not recommended for a myeloablative regimen by treating investigator
- STEP 1: Prior venetoclax therapy is allowed unless there is evidence of progression or no response (failure to achieve remission) to venetoclax-based regimen \< 2 months prior to registration
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew J Wieduwilt
Alliance for Clinical Trials in Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- This is a randomized, double-blind trial. Sites will be blinded to treatment assignment.
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2025
First Posted
May 2, 2025
Study Start (Estimated)
July 17, 2026
Primary Completion (Estimated)
May 15, 2028
Study Completion (Estimated)
May 15, 2028
Last Updated
May 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.