Recruiting
Phase 2

ASTX727 & Venetoclax

Sponsor:

National Cancer Institute (NCI)

Code:

NCT07437950

Conditions

Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Decitabine and Cedazuridine

Venetoclax

Study Details

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

Study ID

NCT07437950

Start date

Apr 18, 2027

Status verified date

Aug, 2026

Completion date

Sep 22, 2034

Anticipated

Primary completion date

Sep 22, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Total bilirubin ≤ 3 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional ULN, unless considered elevated due to disease involvement (within 28 days prior to registration)
  • Participants must have a calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration. For creatinine clearance formula see the tools on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx
  • Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 3 or better
  • Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
  • Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
  • Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
  • Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
  • Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
  • Participants must have agreed to have specimens submitted for translational medicine for MRD under MYELOMATCH.

  • Enrollment to this treatment study requires prior enrollment into the myeloMATCH Master Protocol (MYELOMATCH). Participants enrolled in MYELOMATCH will submit bone marrow samples, peripheral blood samples, and buccal swabs to the Molecular Diagnostics Network (MDNet), the Clinical Laboratory Improvement Act (CLIA) laboratory network for myeloMATCH. Refer to MYELOMATCH for submission requirements and directions.
  • In addition to the MYELOMATCH specimens, there will be specimens obtained on treatment for this substudy. These specimens will be derived from procedures performed as part of standard assessments in the clinical care and management of AML with material being sent to the MDNet laboratories as specified. After performing the required tests on the specimens, the MDNet laboratories will send the residual material for biobanking and future research. Therefore, participants must be asked for their consent for the biobanking of specimens for future unspecified research. Participants may refuse this, but it is mandatory for sites to ask participants
  • Participants must be offered the opportunity to participate in specimen banking
  • NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
  • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Study Design

Enrollment

126 participants

Anticipated

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm 1 (ASTX727 with standard duration venetoclax)

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.

experimental: Arm 2 (ASTX727 with shorter duration venetoclax)

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bone Marrow Aspiration

Undergo bone marrow aspiration

Decitabine and Cedazuridine

Given PO

Venetoclax

Given PO

Primary outcome measure

  • Minimal residual disease (MRD) negative complete remission (CR) [ Time Frame: At 180 days ]

Central Contacts and Locations

Locations

Illinois CancerCare-Bloomington

Recruiting

Bloomington, Illinois, United States, 61704

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Canton

Recruiting

Canton, Illinois, United States, 61520

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Carthage

Recruiting

Carthage, Illinois, United States, 62321

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Cancer Care Specialists of Illinois - Decatur

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Decatur Memorial Hospital

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Eureka

Recruiting

Eureka, Illinois, United States, 61530

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Galesburg

Recruiting

Galesburg, Illinois, United States, 61401

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Kewanee Clinic

Recruiting

Kewanee, Illinois, United States, 61443

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Macomb

Recruiting

Macomb, Illinois, United States, 61455

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Ottawa Clinic

Recruiting

Ottawa, Illinois, United States, 61350

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Pekin

Recruiting

Pekin, Illinois, United States, 61554

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peoria

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peru

Recruiting

Peru, Illinois, United States, 61354

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Princeton

Recruiting

Princeton, Illinois, United States, 61356

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Southern Illinois University School of Medicine

Recruiting

Springfield, Illinois, United States, 62702

Contacts

Site Public Contact

217-545-7929

Principal Investigator:

Bryan A. Faller

Springfield Clinic

Recruiting

Springfield, Illinois, United States, 62702

Contacts

Site Public Contact

800-444-7541

Principal Investigator:

Bryan A. Faller

Springfield Memorial Hospital

Recruiting

Springfield, Illinois, United States, 62781

Contacts

Site Public Contact

217-528-7541pallante.beth@mhsil.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare - Washington

Recruiting

Washington, Illinois, United States, 61571

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

LSU Health Baton Rouge-North Clinic

Recruiting

Baton Rouge, Louisiana, United States, 70805

Contacts

Site Public Contact

225-765-7659research@ololrmc.com

Principal Investigator:

Harry G. Sequeira Gross

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Recruiting

Brighton, Michigan, United States, 48114

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology - Canton

Recruiting

Canton, Michigan, United States, 48188

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Recruiting

Chelsea, Michigan, United States, 48118

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Trinity Health Saint Mary Mercy Livonia Hospital

Recruiting

Livonia, Michigan, United States, 48154

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Trinity Health Saint Joseph Mercy Oakland Hospital

Recruiting

Pontiac, Michigan, United States, 48341

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Recruiting

Ypsilanti, Michigan, United States, 48197

Contacts

Site Public Contact

734-712-7251MCRCwebsitecontactform@stjoeshealth.org

Principal Investigator:

Tareq Al baghdadi

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Contacts

Site Public Contact

800-767-9355askroswell@roswellpark.org

Principal Investigator:

Eunice S. Wang

Gundersen Lutheran Medical Center

Recruiting

La Crosse, Wisconsin, United States, 54601

Contacts

Site Public Contact

608-775-2385cancerctr@gundersenhealth.org

Principal Investigator:

David E. Marinier

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 3, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-03.