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Phase 2

ASTX727 & VenetoclaxVenetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05600894

Conditions

Chronic Myelomonocytic Leukemia

Myelodysplastic Syndrome

Myelodysplastic Syndrome With Excess Blasts

Myelodysplastic/Myeloproliferative Neoplasm

Myeloproliferative Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Decitabine and Cedazuridine

Venetoclax

Study Details

Brief summary:

This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Blasts are immature blood cells. 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. The combination of ASTX727 and venetoclax may be more effective in reducing the cancer signs and symptoms in patients with CMML, or MDS/MPN with excess blasts.

Conditions

Chronic Myelomonocytic Leukemia

Myelodysplastic Syndrome

Myelodysplastic Syndrome With Excess Blasts

Myelodysplastic/Myeloproliferative Neoplasm

Myeloproliferative Neoplasm

Study ID

NCT05600894

Start date

Jun 27, 2023

Status verified date

Apr, 2025

Completion date

Aug 31, 2025

Anticipated

Primary completion date

Aug 31, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

132 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

active comparator: 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.

Interventions

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

Primary outcome measure

Complete response rate [ Time Frame: Up to 4 cycles ]

Central Contacts and Locations

Locations

Mayo Clinic Hospital in Arizona

Recruiting

Phoenix, Arizona, United States, 85054

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Talha Badar

UC Irvine Health Cancer Center-Newport

Recruiting

Costa Mesa, California, United States, 92627

Contacts

Site Public Contact

877-827-8839

Principal Investigator:

Deepa Jeyakumar

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Deepa Jeyakumar

UCI Health Laguna Hills

Recruiting

Laguna Hills, California, United States, 92653

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Deepa Jeyakumar

Los Angeles General Medical Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451 uscnorrisinfo@med.usc.edu

Principal Investigator:

Abdullah Ladha

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Abdullah Ladha

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Deepa Jeyakumar

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Brian A. Jonas

Yale University

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Site Public Contact

203-785-5702 canceranswers@yale.edu

Principal Investigator:

Jan P. Bewersdorf

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Talha Badar

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

312-695-1301 cancer@northwestern.edu

Principal Investigator:

Jamile Shammo

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Olatoyosi M. Odenike

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Olatoyosi M. Odenike

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Olatoyosi M. Odenike

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Abdulraheem M. Yacoub

University of Maryland/Greenebaum Cancer Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Site Public Contact

800-888-8823

Principal Investigator:

Sandrine Niyongere

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Public Contact

410-955-8804 jhcccro@jhmi.edu

Principal Investigator:

Ivana Gojo

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

617-667-9925

Principal Investigator:

Malgorzata McMasters

Montefiore Medical Center-Einstein Campus

Recruiting

Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866 eskwak@montefiore.org

Principal Investigator:

Ioannis Mantzaris

Montefiore Medical Center-Weiler Hospital

Recruiting

Bronx, New York, United States, 10461

Contacts

Site Public Contact

718-379-6866 eskwak@montefiore.org

Principal Investigator:

Ioannis Mantzaris

Montefiore Medical Center - Moses Campus

Recruiting

Bronx, New York, United States, 10467

Contacts

Site Public Contact

718-379-6866 eskwak@montefiore.org

Principal Investigator:

Ioannis Mantzaris

NYP/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-746-1848

Principal Investigator:

Gail J. Roboz

UNC Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Site Public Contact

877-668-0683 cancerclinicaltrials@med.unc.edu

Principal Investigator:

Joshua F. Zeidner

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Rupali R. Bhave

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698 cancer@uchealth.com

Principal Investigator:

Emily K. Curran

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066 Jamesline@osumc.edu

Principal Investigator:

Shivani Handa

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698 cancer@uchealth.com

Principal Investigator:

Emily K. Curran

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777 ou-clinical-trials@ouhsc.edu

Principal Investigator:

Manu Pandey

University of Pittsburgh Cancer Institute (UPCI)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Annie P. Im

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100 cancerinfo@hci.utah.edu

Principal Investigator:

Ami Patel

University of Virginia Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Site Public Contact

434-243-6303 uvacancertrials@hscmail.mcc.virginia.edu

Principal Investigator:

Daniel R. Reed

Virginia Commonwealth University/Massey Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

CTOclinops@vcu.edu

Principal Investigator:

Keri R. Maher

University Health Network-Princess Margaret Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Site Public Contact

416-946-4501 clinical.trials@uhn.on.ca

Principal Investigator:

Marta Davidson

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Apr 24, 2025

Last verified

Apr, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-03. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2025-04-24. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.