Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; in High-Risk MDS Added to ASTX727; and Alone in Low Risk MDS (A MyeloMATCH Treatment Substudy)

Sponsor
National Cancer Institute (NCI)
Study ID
NCT07153497
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Biospecimen Collection — PROCEDURE
    Undergo collection of blood samples
  • Bone Marrow Aspiration — PROCEDURE
    Undergo bone marrow aspiration
  • Bone Marrow Biopsy — PROCEDURE
    Undergo bone marrow biopsy
  • Decitabine and Cedazuridine — DRUG
    Given PO
  • Olutasidenib — DRUG
    Given PO
  • Venetoclax — DRUG
    Given PO

Study Details

This phase II MyeloMATCH treatment substudy tests the addition of olutasidenib to usual treatment in patients with higher-risk myelodysplastic syndrome (MDS) or patients with acute myeloid leukemia (AML) with a mutation in the IDH1 gene. Olutasidenib blocks the protein made by the mutated IDH1 gene. Blocking this protein may help keep cancer cells from growing. For patients with MDS, olutasidenib will be added to decitabine-cedazuridine (also called ASTX727). Decitabine is in a class of medications called hypomethylating agents and is the standard treatment for MDS. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The cedazuridine makes it possible to take the decitabine by mouth. Adding olutasidenib to the usual treatment for MDS (ASTX727) may increase the likelihood of going into remission. For patients with AML, olutasidenib and ASTX727 will be combined with venetoclax, a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Adding olutasidenib to the usual treatment for AML (ASTX727 and venetoclax) may increase the likelihood of going into remission. For low risk MDS, the substudy tests whether giving olutasidenib alone helps improve blood counts.

Key Dates

Start date
May 27, 2026
Status verified
Dec 2025
Primary completion
Apr 26, 2030
Completion
Apr 26, 2030

Study Design

Enrollment
132 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Cohort A, Arm 1 (ASTX727, venetoclax)
    Patients receive ASTX727 PO QD on days 1-5 of each cycle and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR, CRh, or CRi after cycle 4 continue treatment cycles every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial.
  • Experimental: Cohort A, Arm 2 (ASTX727, venetoclax, olutasidenib)
    Patients receive ASTX727 PO QD on days 1-5 of each cycle, venetoclax PO QD on days 1-28 of each cycle, and olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR, CRh, or CRi after cycle 4 continue treatment cycles every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial.
  • Experimental: Cohort B, Arm 3 (ASTX727, olutasidenib)
    Patients receive ASTX727 PO QD on days 1-5 of each cycle and olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR continue treatment cycles every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial.
  • Active Comparator: Cohort B, Arm 4 (ASTX727)
    Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients without CR after cycle 6 may then cross-over to Arm 3. Patients with CR, as well as patients without CR but deriving clinical benefit after cycle 6 continue treatment cycles every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial.
  • Experimental: Cohort C (olutasidenib)
    Patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit after cycle 6 continue treatment cycles every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy/aspiration and collection of blood samples throughout the trial.

Primary Outcome Measure

Minimal residual disease (MRD)-negative complete response (CR) + CR with partial hematological recovery (CRh) + CR with incomplete bone marrow recovery (CRi) (Cohort A) [ Time Frame: Up to 4 cycles post randomization (Cycles = 28 days) ]

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