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

Genentech

Status and phase: Completed; Phase 1

Conditions: Lymphocytic Leukemia, Chronic

Treatments: Drug: Venetoclax; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01685892

2012-002038-34 (EudraCT Number)

GP28331

Details and patient eligibility

About

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).

Enrollment: 82 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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82 participants in 6 patient groups

Dose-Finding: Schedule A: Relapsed/Refractory CLL

Experimental group

Description:

All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Dose-Finding: Schedule B: Relapsed/Refractory CLL

Experimental group

Description:

In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Dose-Finding: Schedule A: Previously Untreated CLL

Experimental group

Description:

All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Dose-Finding: Schedule B: Previously Untreated CLL

Experimental group

Description:

In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Safety Expansion: Relapsed/Refractory CLL

Experimental group

Description:

In participants with relapsed/refractory CLL a recommended dose of venetoclax 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.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Safety Expansion: Previously Untreated CLL

Experimental group

Description:

In participants with previously untreated CLL a recommended dose of venetoclax 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.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax