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)

Sponsor
National Cancer Institute (NCI)
Study ID
NCT06954987
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Allogeneic Hematopoietic Stem Cell Transplantation — PROCEDURE
    Given IV
  • Biospecimen Collection — PROCEDURE
    Undergo blood, urine and buccal swab collection
  • Bone Marrow Biopsy — PROCEDURE
    Undergo bone marrow biopsy
  • Busulfan — DRUG
    Given IV
  • Chest Radiography — PROCEDURE
    Undergo chest x-ray
  • Computed Tomography — PROCEDURE
    Undergo CT scan
  • Echocardiography Test — PROCEDURE
    Undergo echocardiography
  • Fludarabine — DRUG
    Given IV
  • Melphalan — DRUG
    Given IV
  • Multigated Acquisition Scan — PROCEDURE
    Undergo MUGA
  • Placebo Administration — DRUG
    Given PO
  • Positron Emission Tomography — PROCEDURE
    Undergo PET scan
  • Total-Body Irradiation — RADIATION
    Undergo total body irradiation
  • Venetoclax — DRUG
    Given PO

Study Details

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.

Key Dates

Start date
Jul 17, 2026
Status verified
Feb 2026
Primary completion
May 15, 2028
Completion
May 15, 2028

Study Design

Enrollment
244 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Conditioning 1A (matched donors with venetoclax)
    Patients 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.
  • Placebo Comparator: Conditioning 1B (matched donor with placebo)
    Patients 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.
  • Experimental: Conditioning 2A (haplo/mismatched donor with venetoclax)
    Patients 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.
  • Placebo Comparator: Conditioning 2B (haplo/mismatched unrelated and placebo)
    Patients 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.
  • Experimental: Maintenance I (venetoclax)
    Patients 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.
  • Placebo Comparator: Maintenance II (placebo)
    Patients 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.

Primary Outcome Measure

Event free survival (EFS) [ Time Frame: From randomization to minimal residual disease (MRD) persistence, MRD relapse, morphologic relapse, or death from any cause, assessed up to day +100 ]

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