A Safety and Efficacy Study of Obinutuzumab Alone or in Combination With Chemotherapy in Participants With Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Bendamustine; Chlorambucil; Cyclophosphamide; Fludarabine; Obinutuzumab
Intervention description: Bendamustine: 90 milligram per millilitre square (mg/m^2) IV over 60 minutes once daily (QD) Day 1-2 in participants previously untreated or 70 mg/m^2 I.V. over 60 minutes QD Day 1-2 in participants with relapsed/refractory disease. In non-fit participants only, investigators may opt at their own discretion to use lower initial doses of bendamustine, i.e., bendamustine 70 mg/m^2 in previously untreated participants, and bendamustine 50 mg/m^2 in relapsed/refractory subjects (over 60 minutes qd Day 1-2 for each administration).; Chlorambucil 0.5 mg/kg p.o. qd on Day 1 and Day 15 in non-fit participants only.; Cyclophosphamide 250 mg/m^2 I.V. over 15-30 minutes qd Day 1-3 or Cyclophosphamide 250 mg/m^2 p.o. QD Day 1-3 in fit participants only.; Fludarabine 25 mg/m^2 I.V. over 30 minutes QD Day 1-3 or Fludarabine 40 mg/m^2 per os (p.o.) QD Day 1-3 in fit participants only.; Participants will receive obinutuzumab 1000 mg IV infusion on Days 1/2 (dose split over 2 consecutive days; 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1, and on Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle is of 28-days duration.
Intervention MeSH terms: Cyclophosphamide; Bendamustine Hydrochloride; Chlorambucil; Fludarabine; Obinutuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 979.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This multicenter, open-label, single-arm study will evaluate the safety and efficacy of
      obinutuzumab alone or in combination with chemotherapy in participants with previously
      untreated or relapsed/refractory chronic lymphocytic leukemia (CLL). This is a
      Post-Authorization Safety Study. Participants will receive 6 cycles of single-agent
      obinutuzumab or obinutuzumab in combination with chemotherapy at the investigator's
      discretion. Each participant will be followed until 30 months after the last participant has
      been enrolled. Total length of the study is anticipated to be approximately 5 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated documented CLL according to National Cancer
             Institute/international workshop on CLL (NCI/iwCLL) criteria OR relapsed and/or
             refractory documented CLL participants requiring treatment according to NCI/iwCLL
             criteria; participants with up to 3 relapses are eligible

          -  Refractory participants if last treatment was with single-agent therapy, single-agent
             chemotherapy, or single-agent antibody

          -  Participants with 17p-deletion and/or p53 mutation may be included at the
             investigator's discretion

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Life expectancy greater than (>) 6 months according to the investigator's opinion

          -  Adequate hematological function

        Exclusion Criteria:

          -  Participants who have received more than 3 previous CLL treatment lines

          -  Documented transformation of CLL to aggressive lymphoma (Richter's transformation)

          -  Participants who are refractory to immunochemotherapy

          -  Participants with abnormal laboratory values

          -  One or more individual organ/system impairment score of 4 as assessed by the
             cumulative illness rating scale (CIRS) definition, excluding the eyes, ears, nose,
             throat and larynx organ systems

          -  Participants with a history of progressive multifocal leukoencephalopathy (PML)

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

          -  Known hypersensitivity to the study drugs

          -  History of prior malignancy unless the malignancy has been treated with a curative
             intent and in remission without treatment for greater than or equal to (>/=) 5 years
             prior to enrollment and with the exception of curatively-treated basal cell carcinoma,
             squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low
             grade, early stage localized prostate cancer treated surgically with curative intent

          -  Regular treatment with corticosteroids during the 28 days prior to the start of Cycle
             1, Day 1, unless administered for indications other than CLL at a dose equivalent to
             less than or equal to (</=) 30 milligrams per day (mg/day) prednisone

          -  Regular treatment with immunosuppressive medications following previous organ
             transplantation

          -  Evidence of significant, uncontrolled concomitant diseases

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of the nail beds) or a major episode of infection
             requiring treatment with intravenous (IV) antibiotics or hospitalization within 28
             days prior to the start of Cycle 1, Day 1

          -  Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1

          -  Major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for
             diagnosis

          -  Positive for chronic hepatitis B, hepatitis C, human T-lymphotropic virus 1 (HTLV 1)
             or human immunodeficiency virus (HIV) infection

          -  Pregnant or lactating women

          -  Fertile men or women of childbearing potential

          -  Participation in another clinical trial with drug intervention within 28 days prior to
             start of Cycle 1, Day 1 and during the study