NCT05365035

A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomonocytic leukemia (CMML).

Detailed description

Primary Objectives: * To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk MDS with excess blasts and higher-risk CMML. * MDS relapsed cohort (Cohort A, N=20): MDS with Int-2 or High risk IPSS and \>5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles * CMML relapsed cohort (Cohort B, N=10): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles * MDS HMA-naïve cohort (Cohort C, N=20): MDS with Int-2 or High risk by IPSS and \>10% blasts OR diagnosis * CMML HMA-naïve cohort (Cohort D, N=10): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of \>5cm below costal margin, platelets \<100x109/L, Hgb level \<10g/dL, WBC \>13x109/L, clonal cytogenetic abnormality (other than monosomy Y). Secondary Objectives: * To evaluate responses by 2015 IWG MDS/MPN response criteria in patients with MDS/MPN and by 2023 IWG response criteria in all patients (Appendix). * To assess overall survival (OS), duration of response, leukemia-free survival (LFS), and relapse-free survival (RFS). * To evaluate proportion of transplant-candidate patients bridged to allogeneic stem-cell transplant. * Correlative studies including correlation of response with disease subtype and genomic profile. * To evaluate changes in clonal composition and VAF of identified mutations with therapy.

Conditions

• Myelodysplastic Syndromes
• Myeloproliferative Chronic Myelomonocytic Leukemia

Interventions

Type	Name	Description
DRUG	Cladribine	Given by Vein (IV)
DRUG	Cytarabine	Given under the skin; subcutaneous injection (SQ)
DRUG	Venetoclax	Given by PO
DRUG	Azacitidine	Given by IV or subcutaneous injection (SQ)

Timeline

• Start date: 2022-09-23
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2022-05-06
• Last updated: 2025-12-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study