Two-Drug cocktail aims to beat back rare bone marrow cancers

NCT ID NCT05600894

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Aug 20, 2026 · Updated 4 times

Summary

This study tests whether adding venetoclax to ASTX727 (a two-in-one pill) works better than ASTX727 alone for people with chronic myelomonocytic leukemia or related bone marrow cancers with too many immature cells. About 132 adults will be randomly assigned to one of the two treatments. The goal is to see if the combination leads to more complete remissions and longer survival.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 132 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jun 2023

Expected to finish

Aug 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * A diagnosis of an MDS/MPN "overlap" syndrome with \>= 5% marrow blasts (including monocytic blast equivalent in case of CMML). Hydroxyurea may be used to control counts up until the start of therapy * White blood cell (WBC) \< 25,000/mm\^3. Treatment with hydroxyurea is permitted to lower the WBC to reach this criterion * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ASTX727 in combination with venetoclax in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN OR =\< 5.0 x institutional ULN for patients with liver metastases * Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2 * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Hormonal therapy for prior or concurrent malignancy is allowed * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) and/or family member available will also be eligible * Ability to swallow pills Exclusion Criteria: * Patients with need for emergent disease-directed therapy excluding hydroxyurea * More than one cycle of previous MDS/MPN-directed therapy, or MDS-directed therapy including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine, excluding hydroxyurea. Prior use of erythropoietin stimulating agents (ESA) and thrombopoietic agents is allowed, but must be discontinued 4 weeks prior to study treatment * Patients currently or previously receiving an investigational agent or device within 4 weeks of the first dose of treatment * Patients with symptomatic uncontrolled central nervous system (CNS) disease. Imaging to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days * Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment and are unwilling to discontinue consumption of these throughout the receipt of study drug * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727 or venetoclax * Patients with uncontrolled intercurrent illness (e.g. requiring intravenous therapy) at the discretion of the investigator * Pregnant women are excluded from this study because venetoclax and ASTX727 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax. These potential risks may also apply to other agents used in this study. Patients must be post-menopausal or with evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1 * Post-menopausal is defined as: * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 years of age * Radiation-induced oophorectomy with last menses \> 1 year ago * Chemotherapy-induced menopause with \> 1 year interval since last menses * Surgical sterilization (bilateral oophorectomy or hysterectomy) * Women of child-bearing potential must agree to use adequate contraception (hormonal birth control or abstinence) prior to study entry and for the duration of study participation, and for 6 months following completion of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception (latex or synthetic condom or abstinence) prior to the study, for the duration of study participation, and 3 months after completion of venetoclax and ASTX727 administration * Patients with any other medical condition for which the expected survival is below 12 months * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or assessment of the investigational regimen * Patients with uncontrolled infection at the time of study entry

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Conditions

The condition(s) this trial relates to.

chronic myelomonocytic leukemia myelodysplastic syndrome myelodysplastic syndrome with excess blasts Myelodysplastic Syndromes myelodysplastic/myeloproliferative disease myelodysplastic/myeloproliferative neoplasm Myeloproliferative Disorders myeloproliferative neoplasm

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Chronic myelomonocytic leukemia Myelodysplastic syndrome Myelodysplastic syndrome with excess blasts Myelodysplastic/myeloproliferative neoplasm Myeloproliferative neoplasm

Contacts and locations

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States
Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States
Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States
Los Angeles General Medical Center

Los Angeles, California, 90033, United States
Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States
Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States
Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States
Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States
NYP/Weill Cornell Medical Center

New York, New York, 10065, United States
Northwestern University

Chicago, Illinois, 60611, United States
Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States
UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States
UC Irvine Health Cancer Center-Newport

Costa Mesa, California, 92627, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States
UCI Health Laguna Hills

Laguna Hills, California, 92653, United States
UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States
UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States
USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States
University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada
University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States
University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States
University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States
University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States
University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States
University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States
Yale University

New Haven, Connecticut, 06520, United States

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