This phase II trial tests whether cladribine, low dose cytarabine, venetoclax, and azacitidine work in treating higher risk myelodysplastic syndrome chronic myelomonocytic leukemia or myelodysplastic syndrome/myeloproliferative neoplasms. Chemotherapy drugs, such as cladribine, cytarabine and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving cladribine, cytarabine, venetoclax, and azacitidine work better in controlling higher risk myelodysplastic syndrome chronic myelomonocytic leukemia or myelodysplastic syndrome/myeloproliferative neoplasms.
Additional locations may be listed on ClinicalTrials.gov for NCT05365035.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Guillermo Montalban Bravo
Phone: 713-794-3604
PRIMARY OBJECTIVE:
I. To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk myelodysplastic syndrome (MDS) with excess blasts and higher-risk chronic myelomonocytic leukemia (CMML) or other MDS/myeloproliferative neoplasms (MPNs).
SECONDARY OBJECTIVES:
I. To evaluate responses by 2015 International Working Group (IWG) MDS/MPN response criteria in patients with MDS/MPN and by 2023 IWG response criteria in all patients.
II. To assess overall survival (OS), duration of response, leukemia-free survival (LFS), and relapse-free survival (RFS).
III. To evaluate proportion of transplant-candidate patients bridged to allogeneic stem-cell transplant.
IV. Correlative studies including correlation of response with disease subtype and genomic profile.
IV. To evaluate changes in clonal composition and variant allele frequency (VAF) of identified mutations with therapy.
OUTLINE:
INDUCTION: Patients receive cladribine intravenously (IV) over 1-2 hours on days 1-3 or 1-4, cytarabine subcutaneously (SC) twice daily (BID) on days 1-5 or 1-7, and venetoclax orally (PO) once daily (QD) on days 1-7 or 1-10 of cycle 1. Cycle 1 treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. Patients with bone marrow blasts < 5% after Cycle 1 may proceed to Consolidation/Maintenance, while patients with >= 5% after Cycle 1 may receive cladribine IV over 1-2 hours on days 1-3, cytarabine SC BID on days 1-5, and venetoclax PO QD on days 1-7 of cycle 2. Cycle 2 treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. Patients without a response (< 5% blasts) after a second Induction cycle discontinue study treatment.
CONSOLIDATION/MAINTENANCE: Patients receive alternating cycles of azacitidine SC over 30-60 minutes on days 1-7 and venetoclax PO QD on days 1-7 every 2 cycles and then cladribine IV over 1-2 hours on days 1-3, cytarabine SC BID on days 1-5, and venetoclax PO QD on days 1-7 every 2 cycles. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
Patients also undergo echocardiograph (ECHO) or multigated acquisition scan (MUGA) at baseline, bone marrow biopsy and aspiration, and collection of blood samples at baseline and on study.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorGuillermo Montalban Bravo
