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

NCT03513562 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-17387NCI-2018-00410
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Lymphocytic Leukemia; Ibrutinib Resistance

Outcome Measures

Primary Outcomes (1)

• Rate of mutation negative status after 12 courses of combination therapy of ibrutinib and venetoclax

  The rate of mutation negative status will be the percentage of patients who have negative testing for ibrutinib resistance mutations in the peripheral blood and bone marrow after 12 courses of combination ibrutinib and venetoclax treatment. Mutation negative status is defined as 1% variant allele frequency by the clinical grade test for mutation.

  Up to 3 years

Secondary Outcomes (4)

• Rate of minimal residual disease negative complete remission after 12 courses of venetoclax and ibrutinib

  Up to 3 years

• Progression-free survival after adding venetoclax to ibrutinib

  From start date of combination therapy up to 3 years

• Overall survival after beginning venetoclax in combination with ibrutinib

  From start date of combination therapy up to 3 years

• Discontinuation rate due to adverse events with combination venetoclax and ibrutinib treatment.

  Up to 3 years

Study Arms (1)

Treatment (venetoclax, ibrutinib)

EXPERIMENTAL

Participants receive venetoclax PO daily on days 1-28 and ibrutinib PO 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 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.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Venetoclax

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (venetoclax, ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (venetoclax, ibrutinib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta

Treatment (venetoclax, ibrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting criteria established in the World Health Organization (WHO) classification of hematologic disorders or International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Currently taking ibrutinib and first took ibrutinib \> 3 months ago
• Presence of a known ibrutinib resistance mutation at ≥ 4% variant allele frequency OR \< 4% with two separate measurements at least 4 weeks apart with increasing variant allele frequency
• Adequate bone marrow function independent of growth factor support at screening unless clearly due to marrow involvement by CLL and/or disease-related immune thrombocytopenia; if cytopenias are due to disease in the bone marrow any degree of cytopenias are allowed; patients with active uncontrolled autoimmune cytopenias are excluded
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• Platelets ≥ 40,000/mm\^3
• Prothrombin time/partial thromboplastin time (PT/PTT) ≤ 1.5 x upper limit of normal (ULN) (unless receiving anticoagulation)
• Total bilirubin ≤ 1.5 x ULN (excepting Gilbert's syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ≤ ULN
• Creatinine clearance ≥ 40 mL/min/1.73m\^2
• Using 24-hour creatinine clearance or modified Cockcroft-Gault equation
• All patients must practice a highly effective method of birth control
• Able to take an absorb pill form oral medications

You may not qualify if:

• Inability to continue taking ibrutinib for any reason
• Treatment with chemotherapy, immunotherapy, radiotherapy, targeted small molecule inhibitors, biologic agents, and/or an investigational therapy for 5 half-lives prior to first study dose of venetoclax; treatment with a biologic agent, such as a monoclonal antibody, for 30 days prior to study treatment; treatment with ibrutinib is allowed
• Need for anticoagulation with a vitamin K antagonist (warfarin); other anticoagulants and antiplatelet agents are allowed
• Treatment with a moderate or strong cytochrome P450 3A4 (CYP3A) inhibitor or inducer within 7 days prior to first dose of venetoclax or need for treatment with a strong CYP3A inhibitor or inducer during the period or the study; patients who have a need for treatment with a moderate CYP3A inhibitor or inducer during venetoclax dose escalation will also be excluded
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
• History of lymphoma (Richter's syndrome) unless in complete remission \> 2 years without relapse
• Known active involvement of the central nervous system by lymphoma or leukemia
• Known infection with the human immunodeficiency (HIV) virus
• A cardiovascular disability status of New York Heart Association Class ≥ 2, defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain
• Positive hepatitis serology:
• Patients with positive hepatitis B surface antigen (HBsAg) consistent with prior vaccination to HBV (i.e., hepatitis B immune status/anti-hepatitis B surface antibody \[anti-HBs+\], anti-HBc-) may participate
• Patients suspected to have false positive serologic studies because of intravenous (IV) immunoglobulin administration are potentially eligible without need for further monitoring if they have negative PCR studies for viral DNA/RNA after discussion with the principal investigator
• Patients with positive hepatitis C serology are excluded unless they have negative hepatitis C virus (HCV) ribonucleic acid (RNA) testing after receiving HCV-specific treatment and the case is discussed with the principal investigator
• Female patients who are pregnant, breast-feeding, or planning to become pregnant
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kerry Rogers, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 1, 2018
• Study Start: March 26, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)