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

NCT07437950 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2026-01049MM1OA-S04U10CA180888
• Study Type: interventional
• Target: 126
• Locations: 2 countries
• Sites: 34

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)

  Will compare the proportion of participants who achieve an MRD negative CR at 180 days between the two arms, including standard-of-care arm with 28 day duration of venetoclax in combination with ASTX727 versus experimental arm with 14 day duration of venetoclax in combination with ASTX727, using hierarchical testing to first assess that 14 days of venetoclax is not more than 12% worse than 28 days of venetoclax and if found to be non-inferior, test whether 14 days of venetoclax results in higher MRD negative CR at 180 days compared to the 28-day arm. 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 (8)

• 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 (AEs)

  Up to 5 years

• Rates of CR, CRi with and without MRD

  Up to 5 years

Study Arms (2)

Arm 1 (ASTX727 with standard duration venetoclax)

ACTIVE COMPARATOR

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 treatment discontinuation. 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 treatment discontinuation. 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)

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)

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)

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/m\^2 of cytarabine, and/or leukapheresis, with a maximum limit of 1 month of exposure
• 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 28 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

Study Sites (34)

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814, United States

RECRUITING

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, 83854, United States

RECRUITING

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, 83864, United States

RECRUITING

Illinois CancerCare-Bloomington

Bloomington, Illinois, 61704, United States

RECRUITING

Illinois CancerCare-Canton

Canton, Illinois, 61520, United States

RECRUITING

Illinois CancerCare-Carthage

Carthage, Illinois, 62321, United States

RECRUITING

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526, United States

RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

RECRUITING

Illinois CancerCare-Eureka

Eureka, Illinois, 61530, United States

RECRUITING

Illinois CancerCare-Galesburg

Galesburg, Illinois, 61401, United States

RECRUITING

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, 61443, United States

RECRUITING

Illinois CancerCare-Macomb

Macomb, Illinois, 61455, United States

RECRUITING

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, 61350, United States

RECRUITING

Illinois CancerCare-Pekin

Pekin, Illinois, 61554, United States

RECRUITING

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

RECRUITING

Illinois CancerCare-Peru

Peru, Illinois, 61354, United States

RECRUITING

Illinois CancerCare-Princeton

Princeton, Illinois, 61356, United States

RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

RECRUITING

Springfield Clinic

Springfield, Illinois, 62702, United States

RECRUITING

Springfield Memorial Hospital

Springfield, Illinois, 62781, United States

RECRUITING

Illinois CancerCare - Washington

Washington, Illinois, 61571, United States

RECRUITING

LSU Health Baton Rouge-North Clinic

Baton Rouge, Louisiana, 70805, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118, United States

RECRUITING

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154, United States

RECRUITING

Trinity Health Saint Joseph Mercy Oakland Hospital

Pontiac, Michigan, 48341, United States

RECRUITING

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

RECRUITING

Centro Comprensivo de Cancer de UPR

San Juan, 00927, Puerto Rico

RECRUITING

San Juan City Hospital

San Juan, 00936, Puerto Rico

RECRUITING

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: September 25, 2026
• Primary Completion (Estimated): September 22, 2034
• Study Completion (Estimated): September 22, 2034
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

US (32); PR (2)