NCT03513562

Venetoclax and Ibrutinib in Treating in Participants With Chronic Lymphocytic Leukemia and Ibrutinib Resistance Mutations

Phase 2 Study of Venetoclax Added to Ibrutinib to Eliminate Ibrutinib Resistance Mutations in CLL

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Ohio State University Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well venetoclax and ibrutinib work in treating participants with chronic lymphocytic leukemia and have developed genetic mutations after previously being treated with ibrutinib. Venetoclax and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. Determine if the addition of venetoclax to ibrutinib therapy can eliminate ibrutinib resistance mutations. SECONDARY OBJECTIVES: I. Determine the rate of minimal residual disease negative complete remission to combination ibrutinib and venetoclax therapy. II. Determine progression-free survival after the addition of venetoclax to ibrutinib. III. Determine overall survival after the addition of venetoclax to ibrutinib. IV. Describe the toxicity profile of venetoclax in combination with ibrutinib in this patient population. EXPLORATORY OBJECTIVES I. Describe changes in variant allele frequency (VAF) of known ibrutinib resistance mutations after the addition of venetoclax. II. Perform BH3 profiling and correlate with response to combination venetoclax and ibrutinib therapy. III. Determine if increased expression of MCL-1 and BCL-XL is a potential mechanism of resistance to venetoclax when given in combination with ibrutinib. IV. Determine potential mechanisms of resistance to ibrutinib and venetoclax combination treatment by whole exome and ribonucleic acid (RNA) sequencing. OUTLINE: This is a dose escalation study of venetoclax. Participants receive venetoclax orally (PO) daily on days 1-28 and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 or 24 courses in the absence of disease progression or unacceptable toxicity. Participants with minimal residual disease (MRD) negativity after 12 or 24 courses discontinue treatment, while participants with MRD positivity continue treatment with venetoclax in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up every 3 months for 2 years and then every 6 months thereafter.

Conditions

• Chronic Lymphocytic Leukemia
• Ibrutinib Resistance

Interventions

Type	Name	Description
DRUG	Ibrutinib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2019-03-26
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2018-05-01
• Last updated: 2026-02-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study