Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm
NCT ID: NCT05600894
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
132 participants
INTERVENTIONAL
2023-06-27
2026-08-31
Brief Summary
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Detailed Description
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I. To evaluate the complete remission rates of ASTX727 and ASTX727 plus venetoclax in subjects with CMML and non-CMML MDS/MPN with excess (\>= 5%) blasts.
SECONDARY OBJECTIVES:
I. To evaluate the overall response rate (complete response \[CR\] + partial response \[PR\] + marrow response with erythroid response) of ASTX727 versus ASTX727 + venetoclax in this patient population.
II. To determine the overall survival, progression-free survival, allogeneic hematopoietic stem cell transplantation rate, clearance of the malignant clone, clonality at time of hematologic remission, number of red cell and platelet transfusions required and toxicity of ASTX727 versus ASTX727 + venetoclax.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (COMBINATION THERAPY): Patients receive ASTX727 orally (PO) once daily (QD) on days 1-5 of each cycle 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 also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
ARM II (MONO THERAPY): Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not have response to treatment may cross over to Arm I. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
After completion of study treatment, patients are followed up every 6 months for 5 years or until death, whichever occurs first.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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Arm I (ASTX727, venetoclax)
Patients receive ASTX727 PO QD on days 1-5 of each cycle 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 also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
Biospecimen Collection
Undergo collection of blood and buccal samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
Venetoclax
Given PO
Arm II (ASTX727)
Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not have response to treatment may cross over to Arm I. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
Biospecimen Collection
Undergo collection of blood and buccal samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
Interventions
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Biospecimen Collection
Undergo collection of blood and buccal samples
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
Venetoclax
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Rory M Shallis
Role: PRINCIPAL_INVESTIGATOR
Yale University Cancer Center LAO
Locations
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Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UCI Health Laguna Hills
Laguna Hills, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Yale University
New Haven, Connecticut, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
University of Virginia Cancer Center
Charlottesville, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Countries
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Other Identifiers
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NCI-2022-08797
Identifier Type: REGISTRY
Identifier Source: secondary_id
10538
Identifier Type: OTHER
Identifier Source: secondary_id
10538
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2022-08797
Identifier Type: -
Identifier Source: org_study_id