Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Lymphocytic Leukemia, Chronic

Treatments: Drug: Chlorambucil; Drug: Venetoclax; Drug: Obinutuzumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02242942

BO25323

CLL14

2014-001810-24 (EudraCT Number)

Details and patient eligibility

About

This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in participants with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The time on study treatment was approximately one year and the follow-up period will be up to 9 years.

Enrollment: 445 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
• CLL requiring treatment according to IWCLL criteria
• Total Cumulative Illness Rating Scale (CIRS score) greater than (>) 6
• Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
• Adequate liver function
• Life expectancy > 6 months
• Agreement to use highly effective contraceptive methods per protocol

Exclusion criteria

• Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richter's transformation or pro-lymphocytic leukemia)
• Known central nervous system involvement
• Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
• An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
• Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• Inadequate renal function
• History of prior malignancy, except for conditions as listed in the protocol if participants have recovered from the acute side effects incurred as a result of previous therapy
• Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks of registration
• Participants with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Hypersensitivity to chlorambucil, obinutuzumab, or venetoclax or to any of the excipients
• Pregnant women and nursing mothers
• Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
• Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
• Requires the use of warfarin, marcumar, or phenprocoumon
• Received agents known to be strong and moderate Cytochrome P450 3A inhibitors or inducers within 7 days prior to the first dose of study drug

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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445 participants in 3 patient groups

Safety Run-in Obinutuzumab + Venetoclax

Experimental group

Description:

Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Obinutuzumab + Chlorambucil

Experimental group

Description:

Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.

Treatment:

Drug: Obinutuzumab

Drug: Chlorambucil

Obinutuzumab + Venetoclax

Experimental group

Description:

Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax