This phase II trial compares the safety and effectiveness of a slow and steady (metronomic) pill combination of decitabine and cedazuridine with venetoclax to standard treatment of azacitidine and venetoclax in treating patients with acute myeloid leukemia that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory), high risk myelodysplastic syndrome or high risk or accelerated phase myeloproliferative neoplasms. 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. Azacitidine stops cells from making deoxyribonucleic acid and may kill cancer cells. It is a type of antimetabolite. Although current standard treatment with azacitidine and venetoclax can work, it often causes severe side effects, such as dangerously low blood counts. This can lead to infections and many patients may have to stop treatment. Giving slow and steady doses of the pill combination of decitabine and cedazuridine may be safe, tolerable, and/or effective compared to standard treatment with azacitidine and venetoclax in treating patients with relapsed or refractory acute myeloid leukemia, high risk myelodysplastic syndrome or high risk or accelerated phase myeloproliferative neoplasms.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07710534.
Locations matching your search criteria
United States
Virginia
Richmond
VCU Massey Comprehensive Cancer CenterStatus: Active
Contact: Keri Renee Maher
Phone: 703-863-2754
PRIMARY OBJECTIVE:
I. Compare safety and tolerability of the arms.
SECONDARY OBJECTIVES:
I. Characterize events of special interest defined as grade 3 or greater adverse events (AEs) with attention to prolonged cytopenias, febrile neutropenia, serious infection, and serious bleeding events for both arms.
II. Estimate the event free survival (EFS) for both arms.
III. Estimate minimal residual disease (MRD) negativity rates in acute myeloid leukemia (AML) for both arms.
IV. Estimate best response rates in AML for both arms.
V. Estimate duration of response (DoR) for both arms.
VI. Estimate overall survival (OS) for both arms.
VII. Estimate of early mortality rate at 30 and 60 days in the relapsed/refractory (R/R) AML cohort for both arms.
VIII. Estimate health care utilization metrics for both arms.
IX. Estimate of quality of life metrics for both arms.
X. Estimate proportion of patients proceeding to allogeneic hematopoietic cell transplant (allo-HCT) for both arms.
EXPLORATORY OBJECTIVE:
I. Compare clonal dynamics of clearance/emergence of disease clones by next-generation sequencing (NGS) and cytogenetic assessment, as it relates to response duration and relapse.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive decitabine and cedazuridine orally (PO) and venetoclax PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may also receive hydroxyurea and cytarabine in cycle 1 only, per investigator discretion. Additionally, patients undergo bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
ARM B: Patients receive azacitidine intravenously (IV) over 10-40 minutes on days 1-7 (or days 5-2 off-2 or 2-2 off-5) of each cycle per standard of care. Patients also receive venetoclax PO on days 1-14 or on days 1-28 of each cycle, depending on the results of bone marrow biopsy. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may also receive hydroxyurea and cytarabine in cycle 1 only, per investigator discretion. Additionally, patients undergo bone marrow biopsy and/or aspiration and blood sample collection throughout the study.
After completion of study treatment, patients are followed at 30 and 60 days then every 3 months for up to 2 years.
Lead OrganizationVCU Massey Comprehensive Cancer Center
Principal InvestigatorKeri Renee Maher
