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

NCT07437950 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-01049MM1OA-S04U10CA180888
• Study Type: interventional
• Target: 126
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Minimal residual disease (MRD) negative complete remission (CR)

  Defined as from date of randomization the first of the following failure events: death from any cause, off protocol therapy without MRD negative CR, relapse from MRD negative CR, off protocol therapy without assessment of CR, off protocol therapy without assessment of MRD. Will be analyzed using intent-to-treat principles among eligible participants.

  At 180 days

Secondary Outcomes (7)

• Event free survival

  From randomization to first of: date off protocol therapy without complete remission (CR), CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh), relapse from CR, CRi, or CRh, or death from any cause, up to 5 years

• Relapse free survival

  From the date of achievement of a remission until the date of relapse or death from any cause, up to 5 years

• Overall survival

  From day of randomization on study until death from any cause, up to 5 years

• Incidence of adverse events

  Up to 5 years

• Mechanisms of resistance

  Up to 5 years

Study Arms (2)

Arm 1 (ASTX727 with standard duration venetoclax)

EXPERIMENTAL

Patients receive ASTX727 PO 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Decitabine and Cedazuridine; Drug: Venetoclax

Arm 2 (ASTX727 with shorter duration venetoclax)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Decitabine and Cedazuridine; Drug: Venetoclax

Interventions

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX 727, ASTX-727, ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inaqovi, Inqovi

Arm 1 (ASTX727 with standard duration venetoclax); Arm 2 (ASTX727 with shorter duration venetoclax)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm 1 (ASTX727 with standard duration venetoclax); Arm 2 (ASTX727 with shorter duration venetoclax)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm 1 (ASTX727 with standard duration venetoclax); Arm 2 (ASTX727 with shorter duration venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Arm 1 (ASTX727 with standard duration venetoclax); Arm 2 (ASTX727 with shorter duration venetoclax)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have been assigned to this clinical trial via MATCHBox prior to registration to this study.
• Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
• Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by
• Having ≥ 20% blasts in the bone marrow and/or peripheral blood or
• Having recurrent AML-specific genetic abnormalities with ≥ 10% blasts in the bone marrow aspirate and/or peripheral blood
• Participants with acute promyelocytic leukemia (APL) with PML-RARA are not eligible
• Participants must not have FLT3 mutations (ITD or TKD)
• Participants must not have TP53 mutations
• Participants must not be receiving or planning to receive any other investigational agents while on protocol therapy
• Participants must not have received prior therapy for AML, myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) with the exception of hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, colony-stimulating factors, erythropoiesis-stimulating agents, thrombopoietin receptor agonist, lenalidomide, immunosuppressive therapy, intrathecal chemotherapy, a cumulative dose of up to 1 g/m2 of cytarabine, and/or leukapheresis.
• Note: White blood cell (WBC) must be \< 25 x 10\^9/L prior to start of treatment. Hydroxyurea, leukapheresis, and cytarabine ≤ 1g/m2 are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped prior to initiation of protocol therapy
• Participant must be ≥ 60 years old at the time of registration
• Participant must have been declared unfit for intensive therapy by the treating physician at the time of registration to MYELOMATCH
• Participant must have Zubrod Performance Status of 0-3 within 14 days prior to registration
• Participant must have a complete medical history and physical exam within 28 days prior to registration

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Specimen Handling; decitabine and cedazuridine drug combination; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Uma M Borate

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: February 27, 2026
• Study Start (Estimated): October 14, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: May 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share