A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Obinutuzumab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Bendamustine; Rituximab
Intervention description: Obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.; Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.; Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.; Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.; Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.; Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.; Rituximab 375 milligrams per square meter (mg/m^2) IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.
Intervention MeSH terms: Prednisone; Cyclophosphamide; Bendamustine Hydrochloride; Rituximab; Doxorubicin; Vincristine; Obinutuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1401.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, randomized study will assess the efficacy and safety of obinutuzumab
      (RO5072759) in combination with chemotherapy compared to rituximab (MabThera/Rituxan) with
      chemotherapy followed by obinutuzumab or rituximab maintenance in participants with untreated
      advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, participants
      achieving response (Complete response [CR] or partial response [PR]) will undergo a
      maintenance period continuing on the randomized antibody treatment alone every 2 months until
      disease progression for a total of 2 years. Anticipated time on study treatment is up to
      approximately 2.5 years. After maintenance or observation, participants will be followed for
      5 years until progression. After progression, participants will be followed for new
      anti-lymphoma therapy and overall survival until the end of the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cluster of differentiation 20 (CD20)-positive indolent B-cell non-Hodgkin's lymphoma
             (follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma)

          -  Stage III or IV disease, or Stage II bulky disease (defined as tumor diameter greater
             than or equal to [>/=] 7 centimeters [cm])

          -  For participants with follicular lymphoma: requirement for treatment according to
             Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria

          -  For participants with symptomatic splenic, nodal, or non-gastric extranodal marginal
             zone lymphoma: disease that is de novo or has relapsed following local therapy (i.e.
             surgery or radiotherapy) and requires therapy as assessed by the investigator

          -  At least one bi-dimensionally measurable lesion (greater than [>] 2 cm in its largest
             dimension by computed tomography [CT] scan or magnetic resonance imaging [MRI])

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          -  Adequate hematologic function

        Exclusion Criteria:

          -  Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of
             transformation to a high-grade or diffuse large B-cell lymphoma

          -  Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's
             macroglobulinaemia

          -  Ann Arbor Stage I disease

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

          -  Known hypersensitivity to any of the study drugs or sensitivity to murine products, or
             history of sensitivity to mannitol

          -  For participants with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma
             with chemotherapy, immunotherapy, or radiotherapy

          -  For participants with non-follicular lymphoma: prior treatment with chemotherapy or
             immunotherapy

          -  Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle
             1

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results

          -  For participants who will be receiving cyclophosphamide, doxorubicin, vincristine, and
             prednisone (CHOP): left ventricular ejection fraction (LVEF) less than (<) 50% by
             multiple-gated acquisition (MUGA) scan or echocardiogram

          -  History of prior other malignancy with the exception of curatively treated basal or
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time
             prior to study

          -  Known active infection, or major episode of infection within 4 week prior to the start
             of Cycle 1

          -  Vaccination with a live vaccine within 28 days prior to randomization

          -  Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for
             diagnosis

          -  Abnormal laboratory values as defined by protocol for creatinine, creatinine
             clearance, aspartate transaminase (AST) or alanine transaminase (ALT), total
             bilirubin, international normalized ration (INR), partial thromboplastin time (PTT) or
             activated partial thromboplastin time (aPPT), unless these abnormalities are due to
             underlying lymphoma

          -  Positive test results for human immunodeficiency virus (HIV), human T-lymphotropic
             virus 1 (HTLV1), hepatitis C or chronic hepatitis B

          -  Pregnant or lactating women

          -  Life expectancy <12 months

          -  Participation in another clinical trial with drug intervention within 28 days prior to
             start of Cycle 1 and during study