Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
Purpose
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.
Condition
- B-cell Lymphoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Axicabtagene Ciloleucel |
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered. |
|
More Details
- Status
- Completed
- Sponsor
- Kite, A Gilead Company