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

Myelodysplastic Syndromes Clinical Trial

Official title: 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

Clinical Trial 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).

Clinical Trial 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 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. ;

Related Conditions & MeSH terms

• Anemia, Refractory, with Excess of Blasts
• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

• NCT number: NCT05365035
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Guillermo Bravo, MD
• Phone: (713) 794-3604
• Email: gmontalban1@mdanderson.org
• Status: Recruiting
• Phase: Phase 2
• Start date: September 23, 2022
• Completion date: February 1, 2025