Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Condition: B-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Intervention: Axicabtagene Ciloleucel; Fludarabine; Cyclophosphamide
Intervention description: A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells; Administered according to package insert; Administered according to package insert
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Axicabtagene ciloleucel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in
      participants with high-risk large B-cell lymphoma.

      After the end of KTE-C19-112 (ZUMA-12), participants who received an infusion of axicabtagene
      ciloleucel will complete the remainder of the 15-year follow-up assessments in a separate
      long-term follow-up study, KT-US-982-5968.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Histologically confirmed large B-cell lymphoma

          -  High-grade large B-cell lymphoma

          -  Individuals must have a positive interim positron emission tomography (PET) per
             Cheson, 2014 (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of
             chemoimmunotherapy

          -  No evidence, suspicion and/or history of central nervous system (CNS) involvement of
             lymphoma

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Absolute neutrophil count ≥ 1000/μL

          -  Platelet count ≥ 75,000/μL

          -  Absolute lymphocyte count ≥ 100/μL

          -  Adequate renal, hepatic, pulmonary, and cardiac function defined as:

               -  Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min

               -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5
                  upper limit of normal (ULN)

               -  Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome

          -  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

          -  History of Richter's transformation of chronic lymphocytic leukemia or primary
             mediastinal B-cell lymphoma

          -  History of autologous or allogeneic stem cell transplant

          -  Prior CD19-targeted therapy

          -  Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy

          -  Presence or suspicion of fungal, bacterial, viral, or other infection that is
             uncontrolled or requiring IV antimicrobials for management

          -  History of human immunodeficiency virus (HIV) infection or acute or chronic active
             hepatitis B or C infection

          -  Presence of any indwelling line or drain dedicated central venous access catheters,
             such as a Port-a-Cath or Hickman catheter, are permitted

          -  Individuals 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

          -  History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
             other clinically significant cardiac disease within 12 months of enrollment

          -  History of autoimmune disease 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

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.