Venetoclax and Vincristine Liposomal in Treating Patients With Relapsed or Refractory T-cell or B-cell Acute Lymphoblastic Leukemia

Recurrent Adult Acute Lymphoblastic Leukemia Clinical Trial

Official title: A Phase IB/II Study of Venetoclax (ABT-199) in Combination With Liposomal Vincristine in Patients With Relapsed or Refractory T-Cell or B-Cell Acute Lymphoblastic Leukemia

Status Recruiting

Clinical Trial Summary

This phase Ib/II clinical trial studies the side effects and best dose of venetoclax and how well it works when given together with vincristine liposomal in treating patients with T-cell or B-cell acute lymphoblastic leukemia that has come back or does not respond to treatment. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vincristine liposomal, 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. Giving venetoclax together with vincristine liposomal may work better in treating patients with acute lymphoblastic leukemia.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of venetoclax in combination with vincristine liposomal (liposomal vincristine) in patients with relapsed or refractory T-cell and B-cell acute lymphoblastic leukemia (ALL). (Phase I) II. Safety assessment and toxicity characterization after treatment of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory T-cell and B-cell ALL. (Phase I) III. To determine the preliminary efficacy of venetoclax in combination with liposomal vincristine to induce complete remission (CR) by day 70 in patients with relapsed or refractory T-cell and B-cell ALL. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival, overall survival and toxicity after the combination treatment in patients with relapsed or refractory T-cell and B-cell ALL. (Phase II)

TERTIARY OBJECTIVES:

I. To determine if genetic signature as determined by next generation sequencing can predict response to combination. (Phase II) II. To determine if immunophenotype of ALL is associated with response to combination. (Phase II) III. To determine if the BH3 profile is associated with response to combination. (Phase II) IV. To determine if relative expression of BCL-2 measure by flow cytometry is associated with response to combination. (Phase II)

OUTLINE: This is a phase Ib, dose-escalation study of venetoclax, followed by a phase II study.

Patients receive venetoclax orally (PO) once daily (QD) on days 1-42 of course 1 and days 43-70 of course 2. Patients also receive vincristine liposomal intravenously (IV) weekly for 4 weeks starting on day 14 of course 1.

After completion of study treatment, patients are followed up every 6 months for 5 years. ;

Related Conditions & MeSH terms

• B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoblasts 5 Percent or More of Bone Marrow Nucleated Cells
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia
• T Acute Lymphoblastic Leukemia

• NCT number: NCT03504644
• Study type: Interventional
• Source: Eastern Cooperative Oncology Group
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 13, 2018
• Completion date: December 31, 2028