NCT07437950

Comparing Different Treatment Lengths for Venetoclax in Older People With Newly Diagnosed Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)

A Randomized Phase II Trial of ASTX727 With Standard Duration Versus Shorter Duration of Venetoclax in Genomically Heterogenous AML Among Adults Aged 60 or Older and Less Fit for Intensive Therapy: A MyeloMATCH Substudy

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 126 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

This phase II MyeloMATCH treatment trial compares ASTX727 with standard duration versus shorter duration of venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML). ASTX727 is a combination of decitabine and cedazuridine. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. 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. Shorter duration venetoclax may be as effective as standard duration venetoclax when given with ASTX727 for the treatment of newly diagnosed AML.

Detailed description

PRIMARY OBJECTIVES: I. To compare whether the proportion of participants with a measurable residual disease (MRD) negative complete remission (CR) at 180 days (6 months) is not more than 12% worse between participants randomized to venetoclax for 14 days versus 28 days per cycle (non-inferiority assessment). II. If 14 days of venetoclax is found to be non-inferior to 28 days, to test whether the proportion of participants with an MRD-negative CR at 180 days (6 months) after randomization is significantly higher in the 14 days per cycle compared to the 28-days per cycle (superiority assessment). SECONDARY OBJECTIVES: I. In each arm, to estimate the frequency and severity of toxicities. II. In each arm, to estimate CR rates, CR with incomplete count recovery (CRi) (CRi, with and without MRD) rates, event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) for each of the regimens. III. In each arm, to use the disease characteristics from MATCHBox to describe mechanisms of resistance (and disease sensitivity) across the treatment arms. IV. In each arm, to tabulate the number of cycles competed, percent of cycles with at least one dose reduction, and percent of cycles with at least one treatment delay at 180 days (6 months) after randomization. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive decitabine and cedazuridine (ASTX727) orally (PO) once daily (QD) on days 1-5 and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study. ARM 2: Patients receive ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up periodically for up to 5 years.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2026-10-14
• Primary completion: 2029-05-31
• Completion: 2029-05-31
• First posted: 2026-02-27
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study