Overview

This trial is active, not recruiting.

Condition lymphocytic leukemia, chronic
Treatments obinutuzumab, venetoclax (gdc-0199; abt-199)
Phase phase 1
Targets BCL-2, CD20
Sponsor Genentech, Inc.
Collaborator AbbVie (prior sponsor, Abbott)
Start date November 2012
End date May 2019
Trial size 81 participants
Trial identifier NCT01685892, 2012-002038-34, GP28331, NCT02339181

Summary

This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of venetoclax (GDC-0199; ABT-199) administered in combination with obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia. All participants (relapsed/refractory and previously untreated) will receive 6 cycles of obinutuzumab and venetoclax. After completing combination treatment, previously untreated participants will receive single agent venetoclax for at least 6 additional months (the anticipated time on treatment for previously untreated participants is at least 12 months). After completing combination treatment, relapsed/refractory participants will continue single agent venetoclax until disease progression.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.
(Experimental)
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.
(Experimental)
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.
(Experimental)
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.
(Experimental)
In participants with relapsed/refractory CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.
(Experimental)
In participants with previously untreated CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.
obinutuzumab GA101; RO5072759
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
venetoclax (gdc-0199; abt-199) ABT-199; GDC-0199
Multiple doses of venetoclax are administered orally once daily.

Primary Outcomes

Measure
Maximum Tolerated Dose (MTD)
time frame: Approximately 30 months

Secondary Outcomes

Measure
Percentage of Participants with Complete Response (CR)
time frame: Approximately 30 months
Objective Response (OR)
time frame: Approximately 30 months
Duration of OR
time frame: Approximately 30 months
Overall Survival (OS)
time frame: Approximately 30 months
Progression-Free Survival (PFS)
time frame: Approximately 30 months
Pharmacokinetics: Minimum Plasma Concentration (Cmin)
time frame: Approximately 30 months
Pharmacokinetics: Time to Maximum Concentration (Tmax)
time frame: Approximately 30 months
Pharmacokinetics: Maximal Plasma Concentration (Cmax)
time frame: Approximately 30 months
Safety: Percentage of Participants with Adverse Events (AEs)
time frame: Approximately 30 months
Safety: Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Laboratory Tests and Vital Signs
time frame: Approximately 30 months
Safety: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs)
time frame: Approximately 30 months
Change in Number of B-Cells
time frame: Approximately 30 months
Change in Number of T-Cells
time frame: Approximately 30 months
Change in Number of Natural Killer (NK) Cells
time frame: Approximately 30 months
Change in Serum Immunoglobulin Level
time frame: Approximately 30 months
Pharmacokinetics: Area Under the Concentration Time Curve (AUC)
time frame: Approximately 30 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Diagnosis of relapsing/refractory or previously untreated chronic lymphocytic leukemia - Eastern Cooperative Oncology Group (ECOG) performance score of /= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer - Men must remain abstinent or use a condom plus an additional contraceptive method that together results in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab. Exclusion Criteria: - Infection with human immunodeficiency virus, hepatitis B, or hepatitis C - Uncontrolled autoimmune hemolytic anemia or thrombocytopenia - Investigational or anti-cancer therapy within 5 half-lives of first drug administration - History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease

Additional Information

Official title A Phase Ib Multicenter Dose-Finding and Safety Study Of Venetoclax and Obinutuzumab in Patients With Relapsed or Refractory or Previously Untreated Chronic Lymphocytic Leukemia
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Genentech, Inc..