A Study of Venetoclax in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia

Genentech, Inc.82 enrolled

Overview

This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics as well as the preliminary efficacy of venetoclax (GDC-0199; ABT-199) administered in combination with obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). The study is comprised of two stages for each participant population: a dose-finding stage and a safety-expansion stage. The dose-finding stage will explore multiple doses of venetoclax to be used in combination with a fixed dose of obinutuzumab. The dose-finding stage will also explore two schedules for drug administration, Schedule A (venetoclax introduced before obinutuzumab) and Schedule B (venetoclax introduced after obinutuzumab).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphocytic Leukemia, Chronic

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of relapsing/refractory or previously untreated chronic lymphocytic leukemia * Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 1 * Adequate bone marrow function * Adequate coagulation, renal and hepatic function * For all participants, agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1% per year during the treatment period and for at least 90 days (30 days for women) after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer Exclusion Criteria: * Participants who have undergone allogenic stem cell transplant are ineligible unless they meet the following criteria, a) participants who are off all immunosuppressive therapy, b) participants who have no signs and/or symptoms of acute or chronic graft versus host disease, or c) participants must have appropriate hematology counts * Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C * Uncontrolled autoimmune hemolytic anemia or thrombocytopenia * Investigational or anti-cancer therapy within 5 half-lives prior to the first dose of study drug * History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease

Locations (10)

UCSD Moores Cancer Center

La Jolla, California, United States

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, United States

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Oncology Associates of Oregon

Springfield, Oregon, United States

SCRI-Tennessee Oncology

Nashville, Tennessee, United States

The Methodist Hospital Research Institute; Academic Office of Clinical Trials

Houston, Texas, United States

St James University Hospital

Leeds, United Kingdom

Leicester Royal Infirmary NHS Trust

Leicester, United Kingdom

Barts and The London School of Medicine and Dentistry; Queen Mary, University of London

London, United Kingdom

Outcomes

Primary Outcomes

Percentage of Participants With Dose Limiting Toxicities (DLTs)

Time frame: Schedule (Sch) A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days)

Maximum Tolerated Dose (MTD) of Venetoclax in Combination with Obinutuzumab

Time frame: Sch A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days)

Secondary Outcomes

Percentage of Participants with Adverse Events

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Area Under the Concentration-Time Curve (AUC) of Venetoclax

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Maximal Plasma Concentration (Cmax) of Venetoclax

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Minimum Plasma Concentration (Cmin) of Venetoclax

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Cmax of Obinutuzumab

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Cmin of Obinutuzumab

Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

Percentage of Participants with Confirmed Complete Response (CR) as Determined by Standard CLL Response Criteria

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Percentage of Participants with Objective Response (Partial Response [PR] or CR [Including Cytopenic CR] as Determined by Standard CLL Response Criteria

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Duration of Objective Response as Determined by Standard CLL Response Criteria

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Overall Survival

Time frame: Baseline up to death or end of study (up to approximately 5 years and 5 months)

Progression-Free Survival as Determined by Standard CLL Response Criteria

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Change from Baseline in Number of B-Cells

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Change from Baseline in Number of T-Cells

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Change from Baseline in Number of Natural Killer (NK) Cells

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Change from Baseline in Serum Immunoglobulin Level

Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)