R/R large B-cell lymphoma.
Conditions
Interventions
Trial group:Axicabtagene Ciloleucel Injection (automated process production), 2.0×10^6 anti-CD19 CAR-T cells/kg body weight, single intravenous infusion
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years old; 2. Signed informed consent form; 3. Histologically confirmed large B-cell lymphoma (LBCL), including the following subtypes defined by WHO 2016 classification: diffuse large B-cell lymphoma, not otherwise specified (activated B-cell type / germinal center B-cell type); high-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangements; diffuse large B-cell lymphoma transformed from follicular lymphoma; T-cell/histiocyte-rich large B-cell lymphoma; diffuse large B-cell lymphoma associated with chronic inflammation; primary cutaneous diffuse large B-cell lymphoma, leg type; EBV-positive diffuse large B-cell lymphoma. 4. Adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) who failed first-line immuno-chemotherapy or relapsed within 12 months after first-line immuno-chemotherapy: (1) Refractory disease is defined as failure to achieve complete response after first-line treatment; subjects intolerant to first-line treatment will be excluded. 1) The best response to first-line treatment is progressive disease (PD); 2) The best response is stable disease (SD) after at least 4 cycles of first-line treatment (e.g., 4 cycles of R-CHOP); 3) The best response is partial response (PR) after at least 6 cycles of treatment with biopsy-proven residual lesions, or disease progression within = 1.0 × 10^9 /L; (2) Platelet count (PLT) >= 75 × 10^9 /L; (3) Absolute lymphocyte count >= 0.1 × 10^9 /L; (4) Creatinine clearance rate (estimated by the Cockcroft-Gault formula) > 60 mL/min; (5) Serum alanine transaminase (ALT) / aspartate transaminase (AST) = 50%, no pericardial effusion confirmed by echocardiography, and no clinically significant abnormalities on electrocardiogram (ECG); (8) Absence of clinically significant pleural effusion; (9) Blood oxygen saturation > 92% under non-oxygen inhalation condition. 12. For female subjects of childbearing potential, serum pregnancy test is negative (females with surgical sterilization or post-menopause for at least 2 years are considered non-fertile). Male and female subjects of childbearing potential agree to adopt highly effective contra
Exclusion criteria
Exclusion criteria: 1. History of other malignant tumors, except for non-melanoma skin tumors, carcinoma in situ (e.g., cervical, bladder, breast) or follicular lymphoma that have not relapsed for more than 3 years. 2. Previous history of Richter’s transformation of chronic lymphocytic leukemia (CLL) and primary mediastinal large B-cell lymphoma. 3. Prior autologous or allogeneic hematopoietic stem cell transplantation. 4. Prior receipt of more than one line of treatment for diffuse large B-cell lymphoma. 5. Prior receipt of CD19-targeted therapy. 6. Received systemic immune stimulants (including but not limited to interferon and IL-2) within 6 weeks or 5 drug half-lives (whichever is shorter) before the infusion of Axicabtagene Ciloleucel Injection. 7. Prior receipt of chimeric antigen receptor-modified cell therapy or other genetically modified T-cell therapy. 8. History of severe immediate hypersensitivity reactions to aminoglycosides, tocilizumab, or any study drugs required in this trial. 9. Uncontrolled or suspected fungal, bacterial, viral or other infections requiring intravenous treatment. Patients with uncomplicated urinary tract infection or uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 10. History of immunodeficiency, including human immunodeficiency virus (HIV) infection; positive Treponema pallidum antibody (TP-Ab); hepatitis B infection (positive hepatitis B surface antigen [HBsAg] with quantitative hepatitis B virus DNA [HBV-DNA] above the lower limit of quantification); hepatitis C infection (positive hepatitis C virus antibody [HCV-Ab] with quantitative hepatitis C virus RNA [HCV-RNA] above the lower limit of quantification). 11. Presence of active tuberculosis infection. 12. Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, indwelling urinary catheter, biliary drainage tube, pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are permitted. 13. Detectable malignant cells in cerebrospinal fluid (CSF), brain metastases, or a history of previously detected malignant CSF cells or brain metastases. 14. Current or prior benign central nervous system (CNS) diseases, such as seizure disorders, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune diseases. 15. Atrial or ventricular lymphoma infiltration in subjects. 16. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, New York Heart Association (NYHA) Class II or higher congestive heart failure, or other clinically significant cardiac diseases within 12 months prior to enrollment. 17. Anticipated or potential emergency conditions requiring urgent treatment within 6 weeks due to rapid tumor progression (e.g., intestinal obstruction, great vessel or airway compression). 18. Autoimmune diseases requiring systemic administration of immunosuppressants or immunomodulators within the past 2 years. 19. Diagnosis of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans organizing pneumonia), drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonitis indicated on chest CT. A history of radiation pneumonitis (fibrosis) within the radiation field is allowed. 20. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment. 21. Any concomitant disease that may affect or interfere with safet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Optimal objective response rate;Cytokine release syndrome (CRS) ;Adverse Events (AEs) and Serious Adverse Events (SAEs);Pharmacokinetics;Pharmacodynamics (PD); | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response rate (CRR); Duriation of response (DOR);Progression-frees survival (PFS);Overall survival(OS); | — |
Countries
China
Contacts
Public ContactTing Niu
West China Hospital, Sichuan University
Outcome results
None listed