A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+Obinutuzumab (GA101) in Participants With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN)
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Obinutuzumab; Bendamustine
Intervention description: IV infusion.; IV infusion.
Intervention MeSH terms: Bendamustine Hydrochloride; Obinutuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 413.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: follicular; follicular lymphoma

Summary:

      This open-label, multicenter, randomized Phase III study will investigate the efficacy,
      safety, pharmacokinetics and pharmacoeconomics of obinutuzumab (RO5072759, GA101) combined
      with bendamustine followed by continued obinutuzumab treatment (maintenance monotherapy)
      compared with bendamustine alone treatment in participants with rituximab-refractory indolent
      Non-Hodgkin's lymphoma (iNHL). The end of study was defined to when safety follow-up for all
      patients had been completed (2 years' safety follow-up from last dose).
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of histologically documented, B-lymphocyte antigen cluster of differentiation
             20 plus (CD20+), iNHL

          -  Refractory to any previous regimen containing rituximab (defined by participants who
             did not respond or who progressed during or up to 6 months after treatment with
             rituximab or a rituximab-containing regimen)

          -  Previously treated with a maximum of four unique chemotherapy containing treatment
             regimens

          -  All participants must have at least one bi-dimensionally measurable lesion (greater
             than [>]1.5 centimeters (cm) in its largest dimension by computed tomography [CT]
             scan)

        Exclusion Criteria:

          -  Prior use of any monoclonal antibody (other than anti-CD20) within 3 months prior to
             the start of Cycle 1, prior treatment with obinutuzumab was not allowed

          -  Chemotherapy or other investigational therapy within 28 days prior to the start of
             Cycle 1

          -  Prior treatment with bendamustine (within 2 years of the start of Cycle 1)

          -  Prior allogeneic stem cell transplant

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

          -  History of sensitivity to mannitol

          -  Central nervous system lymphoma or prior diffuse large B-cell lymphoma (DLBCL),
             histological evidence of transformation to high grade or diffuse large B-cell lymphoma

          -  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

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) or any major episode of infection requiring
             treatment with intravenous antibiotics or hospitalization within 4 weeks

          -  Participants with a history of confirmed progressive multifocal leukoencephalopathy
             (PML)

          -  Vaccination with a live vaccine a minimum of 28 days prior to randomization

          -  Recent major surgery (within 4 weeks), other than for diagnosis

          -  Presence of positive test results for Hepatitis B surface antigen (HBsAg); antibody to
             hepatitis B core antigen [anti-HBc]) with detectable viral load (positive hepatitis B
             virus [HBV] deoxyribo-nucleic acid [DNA]) or Hepatitis C

          -  Participants with chronic hepatitis B or seropositive occult (HBV) infection

          -  Participants with seronegative occult HBV infection or past HBV infection (defined as
             anti-HBc positive and HBV DNA negative) could be eligible if they were willing to be
             followed according to the protocol for HBV DNA testing

          -  Participants positive for Hepatitis C virus (HCV) antibody were eligible only if
             polymerase chain reaction(PCR) was negative for HCV Ribonucleic acid (RNA)

          -  Known history of human immunodeficiency virus (HIV) seropositive status

          -  Positive test results for human T-lymphotropic virus type I (HTLV 1) virus in endemic
             countries

          -  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

          -  Ongoing corticosteroid use >30 milligrams per day (mg/day) prednisone or equivalent