NCT04708054

Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 324 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

This phase II trial studies the effect of venetoclax together with busulfan, cladribine, and fludarabine in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing stem cell transplant. Chemotherapy drugs, such as venetoclax, busulfan, cladribine, and fludarabine, 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. Adding venetoclax to the current standard of care stem cell transplant regimen of busulfan, fludarabine, and cladribine may help to control high-risk acute myeloid leukemia or myelodysplastic syndrome.

Detailed description

Phase 2 Portion Primary Objective 1) To obtain preliminary evidence of efficacy as defined by 1-year progression free survival. Secondary Objectives To determine: 1. Safety of this regimen as per NCI toxicity criteria 2. Time to neutrophil and platelet engraftment 3. Incidence of acute and chronic GVHD 4. Relapse incidence 5. Non-relapse mortality 6. Overall survival 7. Graft versus host disease-relapse free survival (GRFS) Phase 3 Portion Primary Objective 1\) To compare progression free survival between two arms Arm 1 Standard of Care: fludarabine + IV busulfan (FluBu) versus Arm 2 Experimental: Venetoclax + Fractionated busulfan, cladribine, and fludarabine Secondary Objectives To compare following between two arms 1. Safety of this regimen as per NCI toxicity criteria 2. Time to neutrophil and platelet engraftment 3. Incidence of acute and chronic GVHD 4. Relapse incidence 5. Non-relapse mortality 6. Overall survival 7. Graft versus host disease-relapse free survival (GRFS)

Conditions

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Busulfan	Given IV
DRUG	Cladribine	Given IV
DRUG	Fludarabine Phosphate	Given IV
PROCEDURE	Hematopoietic Cell Transplantation	Undergo stem cell transplantation
DRUG	Thiotepa	Given IV
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2021-10-21
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2021-01-13
• Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study