Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia

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PRIMARY OBJECTIVES: I. To identify the dose of venetoclax (Bcl-2 inhibitor GDC-0199) that can be safely administered in combination with obinutuzumab and ibrutinib for the treatment of relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). II. To evaluate the feasibility, sa...

PRIMARY OBJECTIVES: I. To identify the dose of venetoclax (Bcl-2 inhibitor GDC-0199) that can be safely administered in combination with obinutuzumab and ibrutinib for the treatment of relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). II. To evaluate the feasibility, safety, and tolerability of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL. III. To determine the minimal residual disease (MRD)-negative complete response (CR) rate after 12 cycles of treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL. SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) and complete response rate (CR) of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL. II. To estimate progression free survival (PFS) after treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL. III. To conduct pharmacokinetic and pharmacodynamic studies of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL. IV. To examine pre-treatment and serial biomarkers associated with response and mechanisms of resistance to venetoclax, obinutuzumab and ibrutinib when given in combination for relapsed/refractory or previously untreated patients with CLL. OUTLINE: This is a phase Ib, dose-escalation study of Bcl-2 inhibitor GDC-0199 followed by a phase II study. Patients receive obinutuzumab intravenously (IV) on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 months for 2 years, and then every 6 months thereafter.

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