Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma

Key Inclusion Criteria

• Histologically proven large B-cell lymphoma (BCL) including the following types defined by World Health Organization (WHO) 2016.
• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified activated B-cell/ germinal center B-cell (ABC/GCB).
• High-grade B-cell lymphoma (HGBL) with or without myelocytomatosis oncogene (MYC) and BCL 2 and/or BCL 6 rearrangement.
• DLBCL arising from follicular lymphoma (FL).
• T-cell/histiocyte rich large B-cell lymphoma.
• DLBCL associated with chronic inflammation.
• Primary cutaneous DLBCL, leg type.
• Epstein-Barr virus (EBV) + DLBCL.
• Relapsed or refractory disease after first-line chemoimmunotherapy.
• Refractory disease defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.
• Progressive disease (PD) as best response to first-line therapy.
• Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP).
• Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy.
• Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy.
• Individuals must have received adequate first-line therapy including at a minimum:
• Anti-Cluster of Differentiation 20 antigen (CD20) monoclonal antibody unless investigator determines that tumor is CD20 negative, and
• An anthracycline containing chemotherapy regimen.
• No known history or suspicion of central nervous system involvement by lymphoma.
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
• Adequate bone marrow function as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1000/μl
• Platelet ≥ 75,000/μl
• Absolute lymphocyte count ≥ 100/μl
• Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
• Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min.
• Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 mg/dl
• Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an Echocardiogram (ECHO), and no clinically significant Electrocardiogram (ECG) findings.
• No clinically significant pleural effusion.
• Baseline oxygen saturation > 92% on room air.

Key Exclusion Criteria

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years.
• Received more than one line of therapy for DLBCL.
• History of autologous or allogeneic stem cell transplant.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or anti-hepatitis C virus (HCV) positive. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
• History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment.
• History of symptomatic deep vein thrombosis or pulmonary embol