A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)
Condition: Lymphocytic Leukemia, Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Fludarabine; Obinutuzumab; Bendamustine; Cyclophosphamide
Intervention description: Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.; Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.; Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.; Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.
Intervention MeSH terms: Cyclophosphamide; Bendamustine Hydrochloride; Fludarabine; Obinutuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, 2-arm, nonrandomized, multicenter, Phase Ib study will investigate the
      safety and efficacy of obinutuzumab (RO5072759; GA101) administered in combination with
      chemotherapy (bendamustine or fludarabine + cyclophosphamide [FC] regimens) in participants
      with previously untreated cluster of differentiation 20 (CD20)-positive B-CLL. Participants
      will be enrolled to receive a maximum of 6 cycles of obinutuzumab (1000 milligrams [mg]
      intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus
      bendamustine (90 milligrams per meter square [mg/m^2] IV, on Days 2 and 3 of Cycle 1 and Days
      1 and 2 of Cycles 2 - 6) on 28 day cycles or a maximum of 6 cycles of obinutuzumab (1000 mg
      IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus FC (fludarabine
      25 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2 - 6;
      cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2
      - 6) on 28 day cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of CD20-positive B-CLL

          -  Rai Stage III/IV or Binet Stage C disease

          -  Rai Stage I/II or Binet Stage B disease that requires treatment

          -  Adequate baseline bone marrow function, unless there is clear evidence of extensive
             bone marrow involvement with tumor infiltration, myelodysplasia, or hypocellularity

          -  No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Life expectancy of greater than (>) 6 months

        Exclusion Criteria:

          -  Treatment with any other investigational agent or participation in another clinical
             trial within 28 days prior to the start of Cycle 1

          -  Transformation of CLL to aggressive B-cell malignancy

          -  Creatinine clearance less than equal to (<=) 60 milliliters per minute (mL/min),
             calculated according to the formula of Cockcroft and Gault

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the
             upper limit of normal (ULN)

          -  Total bilirubin greater than equal to (>=) 3 x ULN

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

          -  History of sensitivity to mannitol (if bendamustine is to be administered)

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease or pulmonary disease

          -  Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding
             fungal infections of nail beds) or any major episode of infection requiring treatment
             with IV antibiotics or hospitalization (related to the completion of the course of
             antibiotics) within 4 weeks before the start of Cycle 1

          -  Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for
             diagnosis

          -  Known infection with human immunodeficiency virus (HIV) seropositive status

          -  Presence of positive test results for hepatitis B (hepatitis B virus [HBV] surface
             antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C
             (hepatitis C virus [HCV] antibody serology testing). Participants with chronic HBV
             infection, occult HBV infection, or past HBV infection will be excluded. Participants
             who have received IV immunoglobulin within 3 months of enrollment and who are anti-HBc
             positive but HBV deoxyribonucleic acid (DNA) negative will be considered for inclusion
             on the study by the Medical Monitor on a case-by-case basis. Participants positive for
             HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV
             ribonucleic acid (RNA).

          -  Women who are pregnant or lactating

          -  Fertile men or women of childbearing potential unless 1) surgically sterile or 2)
             using an adequate measure of contraception such as oral contraceptives, intrauterine
             device, or barrier method of contraception in conjunction with spermicidal jelly

          -  Concurrent (or within 7 days prior to the first dose of study treatment) systemic
             corticosteroid use except low-dose corticosteroid therapy used to treat an illness
             other than lymphoma