Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL

Exclusion Criteria

• •Subjects who meet any of the following criteria will be excluded from the study:
• •1. History of central nervous system (CNS) diseases, including but not limited to:
• •* Epilepsy
• •* Paralysis
• •* Aphasia
• •* Stroke
• •* Severe brain injury
• •* Dementia
• •* Parkinson's disease
• •* Neuropathy
• •2. History of autoimmune diseases requiring systemic immunosuppressive therapy within 2 years prior to signing the ICF, including but not limited to:
• •* Crohn's disease
• •* Rheumatoid arthritis
• •* Systemic lupus erythematosus (SLE)
• •* Systemic sclerosis
• •* Inflammatory bowel disease (IBD)
• •* Vasculitis
• •* Psoriasis
• •3. Presence of any uncontrolled active infection at the time of signing the ICF or within 4 weeks prior to apheresis that requires antibiotic, antiviral, or antifungal treatment.
• •4. Positive virological or infectious disease markers, including:
• •* Hepatitis B virus (HBV): Subjects with positive HBsAg or HBcAb-positive at screening must have undetectable HBV DNA in peripheral blood to be eligible; otherwise, they should be excluded.
• •* Hepatitis C virus (HCV): Subjects with positive HCV antibodies and detectable HCV RNA should be excluded.
• •* Human immunodeficiency virus (HIV) antibody-positive subjects should be excluded.
• •* Cytomegalovirus (CMV) DNA test-positive subjects should be excluded.
• •* Epstein-Barr virus (EBV) DNA test-positive subjects should be excluded.
• •* Positive serological or non-specific antibodies for Treponema pallidum (syphilis).
• •5. Clinically significant cardiovascular diseases, including any of the following:
• •1. QTc interval ≥480 ms (Fridericia correction formula)
• •2. New York Heart Association (NYHA) Class II or higher heart failure
• •3. Unstable angina or acute myocardial infarction within 6 months prior to signing the ICF
• •4. Left ventricular ejection fraction (LVEF) \<50%
• •5. Poorly controlled hypertension (as determined by the investigator)
• •6. Clinically significant arrhythmias or those requiring antiarrhythmic treatment, including:
• •* Persistent ventricular tachycardia
• •* Ventricular fibrillation
• •* Torsades de pointes
• •* Complete left bundle branch block
• •6. History of severe hypersensitivity or allergy to any components of the study drug.
• •7. Receipt of any investigational drug therapy or other systemic antitumor therapy within 4 weeks before apheresis (or 5 half-lives of the drug, whichever is longer, as determined by the investigator).
• •8. Receipt of extensive radiotherapy within 4 weeks prior to signing the ICF, except for palliative radiotherapy for non-target lesions within 2 weeks before signing the ICF or as expected during the study.
• •9. Unresolved toxicity from prior antitumor therapy that has not returned to Grade 1 or baseline levels at the time of signing the ICF, except for hair loss and pigmentation (per NCI-CTCAE v5.0).
• •10. Requirement for systemic corticosteroids or other immunosuppressive therapy (≥10 mg/day prednisone or equivalent) within 3 days prior to apheresis or during the study period, except for:
• •1. Intranasal, inhaled, or topical steroids, or localized steroid injections (e.g., intra-articular injections)
• •2. Systemic corticosteroids ≤10 mg/day prednisone (or equivalent physiological dose)
• •3. Steroids as prophylaxis for allergic reactions (e.g., pre-medication before contrast-enhanced CT)
• •4. Steroids used for symptomatic treatment of transfusion-related reactions
• •11. Major surgery within 4 weeks prior to signing the ICF (excluding routine biopsy procedures) or planned major surgery during the study period.
• •12. History of active tuberculosis infection within 1 year prior to signing the ICF, except for subjects with a history of tuberculosis more than 1 year ago, provided that the investigator determines there is no evidence of active tuberculosis.
• •13. History of other primary malignancies within 5 years prior to signing the ICF, except for:
• •1. Adequately treated carcinoma in situ of the cervix
• •2. Localized basal cell carcinoma or squamous cell carcinoma of the skin
• •14. Receipt of live-attenuated or inactivated vaccines within 4 weeks before signing the ICF or planned vaccination during the screening period.
• •15. Any other condition or complication that, in the investigator's judgment, may affect adherence to the study protocol or make the subject unsuitable for participation.
• •16. Pregnancy or lactation.