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

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 \<3x UNL) * Serum total bilirubin ≤ 1.5x ULN (≤ 5x ULN if Gilberts Disease) * Serum Creatinine ≤ 1.5x ULN (or estimated GFR of ≥ 40 mL/min/1.73m2 using Cockcroft Gault formula). Women must be post-menopausal, surgically sterile or use reliable forms of contraception while on study. Women of child bearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. These restrictions apply for 12 months (1 year) after the last dose of study drug. * Women of childbearing potential must have a pregnancy test taken (either by serum beta-human chorionic gonadotropin \[B-hCG\]) or urine) and proven negative within 14 days prior to randomization. Women who are pregnant or breastfeeding are ineligible for this study. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. Patients must be accessible for treatment and follow up. Patients randomized on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up. In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient randomization. Exclusion Criteria: * Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumours curatively treated with no evidence of disease for ≥ 3 years. * Active and uncontrolled central nervous system involvement, meningeal or parenchymal. Patients with CNS disease at initial presentation and who are in a CNS CR at the time of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if there is clinical suspicion of active CNS disease. * Major surgery performed within 10 days of randomization. * Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with Hepatitis B serology suggestive of infection are eligible if they are HBV DNA negative and concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus are eligible. * Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of randomization. * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. * Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up. * Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety, interfere with the absorption or metabolism of selinexor tablets, or preclude safe administration of the planned protocol treatment or required follow-up, including (for example): * active, uncontrolled bacterial, fungal, or viral infection; * clinically significant cardiac dysfunction or cardiovascular disease. * Pregnant or lactating females, or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study. * Patients are not eligible if they have a known hypersensitivity to the study drugs or their components.