Study to Evaluate Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory (R/R) Aggressive B-Cell NHL

Inclusion Criteria

• Biopsy proven aggressive B-cell Non-Hodgkin Lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), follicular lymphoma Grade 3B, PMBCL, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent non-Hodgkin's Lymphoma (NHL), (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin Lymphoma. The following histologies are not eligible:
• Lymphoblastic lymphoma
• Burkitt lymphoma
• Mantle cell lymphoma Any histologies not specifically mentioned must be discussed with medical monitor.
• Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
• Biopsy proven confirmation of relapsed disease.
• Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of progressive metabolic disease (PMD), no metabolic response (NMR), partial metabolic response (PMR) as centrally assessed by PET-/ CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PMD as centrally assessed. A pre-salvage scan is required to be submitted to the central reader if a subject had only 1 cycle of pre-salvage chemotherapy.
• Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
• Eastern Cooperative Oncology Group performance status less than or equal to 2
• Intention to proceed to high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplant (HSCT)
• Laboratory parameters:

Hematology:

• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
• Platelets ≥ 75 x 10^9/L

Chemistry:

• Creatinine clearance ≥ 50 mL/min
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
• Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)

Exclusion Criteria

• CMR following S1 chemotherapy
• Treatment within 30 days prior to randomization with another investigational device or drug study (ies).
• Prior anti-CD19-directed therapies
• Prior HDT with autologous HSCT
• Prior allogeneic HSCT
• Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Evidence of CNS involvement by NHL
• Known infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti hepatitis C virus positive)
• History of malignancy other than B-NHL within the past 3 years with the exception of:
• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment
• Adequately treated non-melanoma skin cancer or lentigo maligna
• Adequately treated cervical carcinoma in situ
• Adequately treated breast ductal carcinoma in situ
• Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
• Known sensitivity to immunoglobulins or any of the components to be administered during dosing.
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required procedures.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Female subjects who are pregnant o