Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia
Condition: Lymphocytic Leukemia, Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Chlorambucil; Venetoclax; Obinutuzumab
Intervention description: Chlorambucil 0.5 milligrams per kilogram (mg/kg) orally at Day 1 and Day 15 at of each 28 day cycle for 12 cycles.; Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.; Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Intervention MeSH terms: Venetoclax; Obinutuzumab; Chlorambucil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 445.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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