A Study of Obinutuzumab [RO5072759 (GA101)] in Combination With CHOP Chemotherapy in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma (GATHER)

A Phase II, Open-Label, Multicenter Study of Efficacy, Safety, and Biomarkers in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma Treated With GA101 (RO5072759) in Combination With CHOP Chemotherapy

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.

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