Novel Combination Therapy in the Treatment of Relapsed and Refractory Aggressive B-Cell Lymphoma

The purpose of this study is to find out what effects new combinations of treatment will have this disease. New promising treatment strategies will be added to this study as they are available to be compared against the standard treatment.

Inclusion Criteria: * Patients with histologic diagnosis for one of the following histologies according to the World Health Organization: documented at initial diagnosis or at relapse: * Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell lymphoma, T-cell rich B-cell lymphoma); * Previous indolent lymphoma (follicular lymphoma, marginal zone lymphoma, including extranodal MALT lymphoma, lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at most recent relapse (biopsy proof of transformation is mandatory); * Unclassifiable B-cell lymphoma with indeterminate features between diffuse large B-cell lymphoma and Burkitt lymphoma. * Biopsy proof of disease at initial diagnosis is mandatory. A repeat biopsy in primary refractory disease is preferred but not mandatory to confirm progressive disease. A biopsy at relapse is preferred but not mandatory. Participating centres must designate a local reference expert pathologist who will confirm the diagnosis for the patients enrolled at that centre. * Patients must be CD20+ in order to be eligible for the study. * Clinically and/or radiologically measurable disease (one site bidimensionally measurable). Measurements/ evaluations must be done within 28 days prior to randomization. * Prior FDG-PET scan, if done at baseline, must be positive (known FDG-avid lymphoma) * Patients with de novo aggressive B-cell lymphoma must have relapsed or progressed, or have refractory disease, after 1 prior line of therapy (R-CHOP chemotherapy or equivalent). Patients with histological transformation from low grade lymphoma may have had up to 3 prior treatment regimens. Patients with transformed low grade lymphoma treated with a non-anthracycline regimen may be enrolled at investigator discretion. * Patient age is ≥16 years. Patients older than 65 years of age are not recommended for this study. * ECOG performance status of 0, 1 or 2. * Patient must be considered fit for intensive chemotherapy and ASCT, and an appropriate candidate to receive second-line salvage chemotherapy and ASCT. * Life expectancy \> 90 days. * Laboratory Requirements: (must be done within 14 days of randomization) Hematology: * Granulocytes (AGC) ≥ 1.0 x 10\^9/L (independent of growth factor support) * Platelets ≥ 100 x 10\^9/L (50 x 10\^9/L if bone marrow involvement by lymphoma, independent of transfusion support) Biochemistry: * AST and ALT ≤ 3x ULN (if both are done, both must be \