NCT02250937

Venetoclax and Sequential Busulfan, Cladribine, and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Allogeneic Transplantation Using Venetoclax, Timed Sequential Busulfan,Cladribine, and Fludarabine Conditioning in Patients With AML and MDS

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 2 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial studies how well venetoclax and sequential busulfan, cladribine, and fludarabine phosphate before donor stem cell transplant work in treating patients with acute myelogenous leukemia or myelodysplastic syndrome. Giving chemotherapy before a donor peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.

Detailed description

PRIMARY OBJECTIVE: I. To compare progression free survival of two schedules of venetoclax, timed sequential busulfan, cladribine and fludarabine conditioning regimen in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: I. Compare overall survival between the two schedules. II. Compare non relapse mortality between the two schedules. III. Compare neutrophil and platelet engraftment between the two schedules. IV. Compare acute and chronic graft-versus-host disease (GVHD) between the two schedules. V. Compare cumulative incidence of relapse between the two schedules. VI. Compare grade III/IV toxicity between the two schedules. TERTIARY OBJECTIVES: I. To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To study immune recovery and cytokines (both in plasma and cells). IV. To study BCL-2 family expression, stem cell surface markers and intracellular signaling markers in AML cells at the time of relapse. OUTLINE: PREPARATIVE REGIMEN: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3 and busulfan intravenously (IV) over 3 hours on days -13 and -12. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3. ARM II: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0. After completion of study treatment, patients are followed up for 2.5 years.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic PBSCT
DRUG	Busulfan	Given IV
DRUG	Cladribine	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo allogeneic PBSCT
OTHER	Pharmacological Study	Correlative studies
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2014-10-27
• Primary completion: 2027-10-31
• Completion: 2027-10-31
• First posted: 2014-09-26
• Last updated: 2026-04-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study