A Study of Obinutuzumab [RO5072759 (GA101)] in Combination With CHOP Chemotherapy in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma (GATHER)
Condition: Lymphoma, B-Cell
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: obinutuzumab; cyclophosphamide; doxorubicin; prednisone; vincristine
Intervention description: 1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15.; 750 mg/m^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles.; 50 mg/m^2 IV, Day 1 of each 21-cycle, 6 cycles.; 100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles.; 1.4 mg/m^2 IV, Day 1 of each 21-day cycle, 6 cycles.
Intervention MeSH terms: Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; Obinutuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, multicenter study will evaluate the efficacy and safety of obinutuzumab
      [RO5072759 (GA101)] in combination with CHOP (Cyclophosphamide, Doxorubicin, Vincristine,
      Prednisone) chemotherapy in patients with advanced diffuse large B-cell lymphoma. Patients
      will receive 8 cycles of obinutuzumab (1000 mg intravenously on Day 1 of each 21-day cycle,
      during Cycle 1 obinutuzumab will also be infused on Days 8 and 15) in combination with CHOP
      chemotherapy on Day 1 of cycles 1 to 6. A substudy will investigate the drug-drug interaction
      of obinutuzumab with CHOP chemotherapy agents. For the substudy, an additional cohort of
      approximately 15 patients are planned to be enrolled at a subset of investigational sites.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients, ≥18 years of age

          -  Previously untreated cluster of differentiation antigen 20 (CD20)-positive diffuse
             large B-cell lymphoma

          -  Ann Arbour Stage III/IV and bulky II (mass >10 cm)

          -  At least one bi-dimensionally measurable lesion defined as >1.5 cm in its largest
             dimension by CT scan

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

          -  Left ventricular ejection fraction ≥50%

          -  Adequate hematologic function

        Exclusion Criteria:

          -  Transformed lymphoma (follicular IIIB) if previously treated with chemotherapy or
             immunotherapy

          -  Prior therapy for diffuse large B-cell lymphoma except for nodal biopsy or local
             irradiation

          -  Central nervous system (CNS) lymphoma, primary mediastinal large cell lymphoma,
             primary cutaneous lymphoma, primary effusion lymphoma

          -  Patients who received cytotoxic drugs or rituximab as part of their treatment for
             another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody

          -  Chemotherapy or other investigational therapy within 28 days prior to the start of
             Cycle 1

          -  Contraindication to any of the individual components of CHOP, including prior receipt
             of anthracyclines

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

          -  History of other malignancy, except for curatively treated basal or squamous cell
             carcinoma or melanoma of the skin or in situ carcinoma of the cervix, or malignancy
             treated with or without curative intent and in remission without treatment for ≥2
             years prior to enrolment

          -  Positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human
             T-cell leukemia virus (HTLV-1) infection

          -  Pregnant or lactating women