TCR Reserved and Power3 (SPPL3) Gene Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-ALL

Exclusion Criteria

• •1. Expected survival time \< 3 months per Principal Investigator's opinion.
• •2. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.
• •3. Patients who received any immunocellular or HSCT therapy within 3 months before enrollment.
• •4. Active central nervous system (CNS) leukaemia (CNS-3).
• •5. Clinically active significant CNS dysfunction.
• •6. Known history of irreversible severe neurological toxicity related to previous antileukaemic treatment leading to organic central nervous system lesions.
• •7. Use of previous anti-leukemic therapy within 5 half-lives prior to allogeneic Power3 (SPPL3) knock-out CD19 CAR-T administration; participation in non-interventional registries or epidemiological studies is allowed.
• •8. Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion.
• •9. History of severe immediate hypersensitivity reaction to any of the agents or any component used in this study.
• •10. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management.
• •11. Uncontrolled or active infectious diseases, such as human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B or C, epstein-barr virus (EBV), and cytomegalovirus (CMV) infection.
• •12. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• •13. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement.
• •14. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• •15. Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome).
• •16. Primary immunodeficiency.
• •17. History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• •18. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months of enrollment.
• •19. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• •20. Vaccine ≤ 6 weeks prior to planned start of conditioning regimen.
• •21. Presence of DSAs directed against allogeneic SPPL3 knock-out CD19 CAR-T.
• •22. 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.