A Study of Automated Axicabtagene Ciloleucel for R/R Large B-cell Lymphoma.

A Single-arm, Multicenter Clinical Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel Injection Manufactured by an Automated Process in Patients With Relapsed/Refractory Large B-cell Lymphoma.

This study is a single-arm, multicenter, open-label clinical study evaluating the efficacy and safety of axicabtagene ciloleucel injection manufactured by an automated cell preparation process in adult subjects with relapsed or refractory large B-cell lymphoma (r/r LBCL) as second-line therapy.

This study is a single-arm, multicenter, open-label clinical study evaluating the efficacy and safety of axicabtagene ciloleucel injection manufactured by an automated cell preparation process in adult subjects with relapsed or refractory large B-cell lymphoma (r/r LBCL) as second-line therapy. A total of 12 adult subjects with r/r LBCL who are refractory to first-line immunochemotherapy or who relapse within 12 months after first-line immunochemotherapy will be enrolled. All subjects will undergo leukapheresis, bridging therapy, conditioning chemotherapy, and a single study drug infusion.

Inclusion Criteria:

1. Age 18 years or older at the time of informed consent
2. Has signed the informed consent form (ICF)
3. Histologically proven large B-cell lymphoma
4. Relapsed or refractory disease after first-line chemoimmunotherapy
5. The subject has at least one measurable lesion on imaging
6. No clinical or historical evidence suggestive of lymphoma involvement of the central nervous system (CNS)
7. A washout period of at least 2 weeks or 5 half-lives (whichever is shorter) from the last prior systemic therapy to the signing of the informed consent form.
8. Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1
9. ECOG performance status of 0 or 1
10. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
11. Female subjects of childbearing potential must have a negative serum pregnancy test . Male and female subjects of childbearing potential must agree to use highly effective contraception during the study and for 6 months post-infusion.

Exclusion Criteria:

1. Prior history of other malignancies, with the exception of non-melanoma skin tumors, carcinoma in situ , or follicular lymphoma that have been free of recurrence for more than 3 years.
2. History of Richter's transformation of CLL or PMBCL
3. History of autologous or allogeneic stem cell transplant
4. Received more than one line of therapy for DLBCL
5. Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel
6. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
7. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides or Tocilizumab
8. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management
9. Known history of infection with human immunodeficiency virus (HIV) or Positive test result for anti-Treponema pallidum antibody (TP-Ab) or hepatitis B(HBsAg positive) or hepatitis C virus (anti-HCV positive)
10. Active tuberculosis
11. Presence of any indwelling line or drain
12. Subjects with detectable malignant cells in the cerebrospinal fluid (CSF) or known brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases
13. History or presence of non-malignant CNS disorder
14. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
15. History of clinically significant cardiac disease within 12 months of enrollment
16. Requirement for urgent therapy within 6 weeks due to tumor mass effects, such as bowel obstruction or blood vessel compression or airway obstruction
17. Patients with idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on chest CT are excluded.
18. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
19. Women of childbearing potential who are pregnant or breastfeeding
20. 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