NCT04655755

Venetoclax in Combination With ASTX727 for the Treatment of Treatment-Naive High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

A Phase I/II Study of Venetoclax in Combination With ASTX727 (Cedazuridine/Decitabine) in Treatment-Naïve High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of venetoclax in combination with cedazuridine and decitabine (ASTX727) in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia who have not received prior treatment (treatment-naive). Chemotherapy drugs, such as venetoclax, cedazuridine, and decitabine, 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.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety and tolerability (phase 1) and overall response rate (ORR) (phase 2) of venetoclax in combination with ASTX727 in patients with treatment-naive high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with bone marrow excess blasts \> 5%. SECONDARY OBJECTIVES: I. Rate of complete remission (CR). II. Rate of marrow/morphologic complete remission (mCR). III. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses). IV. Rate of red blood cell (RBC) transfusion independence. V. Rate of platelet (PLT) transfusion independence. VI. Rate of cytogenetic response. VII. Rate of bone marrow blast response. VIII. Time to transformation to acute myeloid leukemia (AML). IX. Duration of response (DOR). X. Overall survival (OS). XI. Progression-free survival (PFS). XII. Disease-free survival (DFS). XIII. Time to next MDS treatment (TTNT). XIV. Event-free survival (EFS). EXPLORATORY OBJECTIVE: I. To investigate the effects of therapy on MDS and to identify biological markers of response to venetoclax and/or its combination with ASTX727. OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II study. Patients receive venetoclax orally (PO) once daily (QD) on days 1-14. Patients also receive ASTX727 PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.

Conditions

• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2021-01-19
• Primary completion: 2026-07-20
• Completion: 2026-07-20
• First posted: 2020-12-07
• Last updated: 2026-02-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study