A Phase 3, Randomized, Open-Label Study Evaluating Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma
The purpose of this study is to evaluate whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy.
18 Years and up
Accepting Healthy Volunteers?
1. Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al, 2016)
- DLBCL not otherwise specified (ABC/GCB)
- HGBL with or without MYC and BCL2 and/or BCL6 rearrangement
- DLBCL arising from FL
- T-cell/histiocyte rich large B-cell lymphoma
- DLBCL associated with chronic inflammation
- Primary cutaneous DLBCL, leg type
- Epstein-Barr virus (EBV) + DLBCL
2. 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
3. Individuals must have received adequate first-line therapy including at a minimum:
- Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
- An anthracycline containing chemotherapy regimen
4. No known history or suspicion of central nervous system involvement by lymphoma
5. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
6. Adequate bone marrow function as evidenced by:
- Absolute neutrophil count (ANC) ≥ 1000/uL
- Platelet ≥ 75,000/uL
- Absolute lymphocyte count ≥ 100/uL
7. 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:
1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
2. Received more than one line of therapy for DLBCL
3. History of autologous or allogeneic stem cell transplant
4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-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.
6. Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
7. 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
8. Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
9. 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
10. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
11. History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years
12. History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7
Note: Other protocol defined Inclusion/Exclusion criteria may apply