A Study of Venetoclax in Combination With Bendamustine + Rituximab or Bendamustine + Obinutuzumab in Participants With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia (CLL)

Genentech

Status and phase: Completed; Phase 1

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Bendamustine; Drug: Venetoclax; Drug: Obinutuzumab; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01671904

GO28440

2012-002351-42 (EudraCT Number)

Details and patient eligibility

About

This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of venetoclax (GDC-0199, ABT-199) administered in combination with bendamustine and rituximab (BR) (MabThera/Rituxan) or bendamustine and obinutuzumab (BG) to participants with first-line (1L)/previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). The study will explore two venetoclax combination regimens in participants with 1L CLL: BR+venetolax (V) and BG+V. Participants with R/R CLL will be administered BR+V.

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of relapsing/refractory or previously untreated CLL
• Eastern Cooperative Oncology Group (ECOG) performance score of less than equal to (</=) 1
• Adequate bone marrow function
• Adequate coagulation, renal and hepatic function
• Hematological values within the limits independent of growth factor support or transfusion unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)

Exclusion criteria

• Participants received an allogeneic stem cell transplant
• Known human immunodeficiency virus (HIV) positivity
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
• Positive test results for chronic hepatitis B infection and hepatitis C virus (HCV)
• Received any anti-cancer therapy including chemotherapy or radiotherapy, steroid therapy for anti-neoplastic intent, and investigational therapy, including targeted small molecule agents within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy
• Significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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84 participants in 3 patient groups

1L CLL BR+V

Experimental group

Description:

Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Venetoclax

1L CLL BG+V

Experimental group

Description:

Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and obinutuzumab (BG). Participants received six 28-day cycles of BG+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician.

Treatment:

Drug: Bendamustine

Drug: Venetoclax

Drug: Obinutuzumab

R/R CLL BR+V

Experimental group

Description:

Participants with relapsed/refractory (R/R) CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with R/R CLL continued single-agent venetoclax until disease progression, death, or unacceptable toxicity.

Treatment:

Drug: Rituximab

Drug: Bendamustine

Drug: Venetoclax