Inclusion Criteria:

• Large B-cell lymphoma with one or more of the following features:
  • HGBL with MYC and BCL2 and/or BCL6 translocations (double-hit or triple-hit) as determined by investigator by fluorescent in situ hybridization; OR
  • Other histologically confirmed large B-cell lymphoma defined by WHO 2016 {Swerdlow 2016} with an IPI score of ≥ 3 at initial diagnosis or anytime between initial diagnosis and enrollment, including the following lymphoma types:
    • DLBCL-NOS, including GCB type and ABC type;
    • Intravascular large B-cell lymphoma;
    • T-cell/histiocyte-rich large B-cell lymphoma;
    • DLBCL associated with chronic inflammation;
    • Epstein-Barr virus + DLBCL-NOS;
    • HGBL-NOS.
• Subjects must have a positive interim PET per the Lugano Classification {Cheson 2014}(Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy as follows:
  • 2 cycles of an anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20 negative) and anthracycline-containing regimen (e.g., DA-EPOCH-R), with or without intrathecal chemotherapy, at the discretion of the investigator per local standard of care for double-hit or triple-hit lymphoma; OR
  • 2 cycles of an anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20 negative) and anthracycline-containing regimen (e.g., R-CHOP) at the discretion of the investigator per local standard of care for large B-cell lymphoma with IPI score of ≥ 3
• At least 2 weeks must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis.  No evidence, suspicion, and/or history of CNS involvement of lymphoma.
• Toxicities due to prior therapy must be stable and recovered to Grade 1 or less (except for clinically non-significant toxicities such as alopecia).
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
  • Absolute neutrophil count ≥ 1000/μL;
  • Platelet count ≥ 75,000/μL;
  • Absolute lymphocyte count ≥ 100/μL;
  • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min;
  • Serum alanine aminotransferase and aspartate aminotransferase ≤ 2.5 upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s syndrome;
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion (except trace or physiological) as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram findings;
  • No clinically significant pleural effusion;
  • Baseline oxygen saturation > 92% on room air.
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential

Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years.
• History of Richter’s transformation of chronic lymphocytic leukemia or PMBCL.
• History of autologous or allogeneic SCT.
• Prior CD19-targeted therapy.
• Prior CAR therapy or other genetically modified T-cell therapy
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management; simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the sponsor’s medical monitor.
• History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection; subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America guidelines or applicable country guidelines.
• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter); dedicated central venous access catheters, such as a Port-A-Cath® or Hickman® catheter, are permitted.
• Subjects with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma.
• History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Requirement for urgent therapy due to tumor mass effects (e.g., blood vessel compression, bowel obstruction, or transmural gastric involvement).
• Primary immunodeficiency.
• History of autoimmune disease (e.g., Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
• Women of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.  Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy or axicabtagene ciloleucel infusion, whichever is longer.
• In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.