A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Condition: Leukemia, Lymphocytic, Chronic, B-Cell
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ibrutinib; Venetoclax; Chlorambucil; Obinutuzumab; Ibrutinib (as Subsequent Therapy)
Intervention description: Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.; Participants will receive venetoclax in combination with ibrutinib for a total of 12 cycles, beginning at Cycle 4. For the first 5 weeks of venetoclax treatment, the treatment dose will be ramped up from 20 to 400 mg.; Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.; Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.; Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.
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: 211.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess progression-free survival (PFS) from treatment with
      ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as
      assessed by an Independent Review Committee (IRC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants who are: (a) greater than or equal to (>=) 65 years old or, (b) 18
             to 64 years old and have at least 1 of the following:

               1. Cumulative Illness Rating Scale (CIRS) score > 6

               2. Creatinine clearance (CrCl) estimated less than (<) 70 milliliter per minute
                  (mL/min) using Cockcroft-Gault equation

          -  Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
             that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria

          -  Measurable nodal disease (by computed tomography [CT]), defined as at least one lymph
             node > 1.5 centimeter (cm) in longest diameter

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or
             equal to (<=) 2

          -  Active CLL/SLL requiring treatment per the iwCLL criteria

        Exclusion Criteria:

          -  Prior anti-leukemic therapy for CLL or SLL

          -  Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation
             detected at a threshold of >10 percent (%) variable allele frequency (VAF)

          -  Major surgery within 4 weeks of first dose of study treatment

          -  Known bleeding disorders (example, von Willebrand's disease or hemophilia)

          -  Central nervous system (CNS) involvement or suspected Richter's syndrome