Lymphocytic Leukemia, Chronic
Conditions
Brief summary
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).
Interventions
DRUGObinutuzumab
Participants will receive IV infusion of obinutuzumab 100 milligrams (mg) on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
DRUGVenetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Sponsors
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLTs) | 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 | 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
| Measure | Time frame |
|---|---|
| Area Under the Concentration-Time Curve (AUC) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Maximal Plasma Concentration (Cmax) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Minimum Plasma Concentration (Cmin) of Venetoclax | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Cmax of Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Cmin of Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
| Percentage of Participants with Confirmed Complete Response (CR) as Determined by Standard CLL Response Criteria | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Percentage of Participants with Adverse Events | 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 | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Overall Survival | 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 | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of B-Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of T-Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Number of Natural Killer (NK) Cells | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Change from Baseline in Serum Immunoglobulin Level | 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 | Baseline up to end of study (up to approximately 5 years and 5 months) |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab | Baseline up to Cycle 6 (1 Cycle=28 days) |
Countries
United Kingdom, United States
Outcome results
None listed