ACTIVE_NOT_RECRUITING

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

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Conditions

Chronic Myelomonocytic LeukemiaMyelodysplastic SyndromeMyelodysplastic Syndrome With Excess BlastsMyelodysplastic/Myeloproliferative NeoplasmMyeloproliferative Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Venetoclax In Combination With ASTX727, an All-ORal TherapY for Chronic Myelomonocytic Leukemia and Other MDS/MPN With Excess Blasts (VICTORY-MDS/MPN): a Randomized, Phase 2 Trial

Quick Facts

Study Start:2023-06-27
Study Completion:2026-08-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05600894

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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
  2. * White blood cell (WBC) \< 25,000/mm\^3. Treatment with hydroxyurea is permitted to lower the WBC to reach this criterion
  3. * 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
  4. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
  5. * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome)
  6. * 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
  7. * Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2
  8. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  9. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  10. * 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
  11. * 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
  12. * 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
  13. * 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
  14. * Ability to swallow pills
  1. * Patients with need for emergent disease-directed therapy excluding hydroxyurea
  2. * 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
  3. * Patients currently or previously receiving an investigational agent or device within 4 weeks of the first dose of treatment
  4. * 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
  5. * 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
  6. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727 or venetoclax
  7. * Patients with uncontrolled intercurrent illness (e.g. requiring intravenous therapy) at the discretion of the investigator
  8. * 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
  9. * Post-menopausal is defined as:
  10. * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  11. * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 years of age
  12. * Radiation-induced oophorectomy with last menses \> 1 year ago
  13. * Chemotherapy-induced menopause with \> 1 year interval since last menses
  14. * Surgical sterilization (bilateral oophorectomy or hysterectomy)
  15. * 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
  16. * Patients with any other medical condition for which the expected survival is below 12 months
  17. * 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
  18. * Patients with uncontrolled infection at the time of study entry

Contacts and Locations

Principal Investigator

Rory M Shallis
PRINCIPAL_INVESTIGATOR
Yale University Cancer Center LAO

Study Locations (Sites)

Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
United States
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, 92627
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
Los Angeles General Medical Center
Los Angeles, California, 90033
United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
United States
Yale University
New Haven, Connecticut, 06520
United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
United States
Northwestern University
Chicago, Illinois, 60611
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
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
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
United States
NYP/Weill Cornell Medical Center
New York, New York, 10065
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
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Rory M Shallis, PRINCIPAL_INVESTIGATOR, Yale University Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-27
Study Completion Date2026-08-31

Study Record Updates

Study Start Date2023-06-27
Study Completion Date2026-08-31

Terms related to this study

Additional Relevant MeSH Terms

  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome
  • Myelodysplastic Syndrome With Excess Blasts
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm