Safety and Efficacy of Anti-CD20/CD30 CAR-T Cells in Subjects with Relapsed/Refractory Lymphoma

Exclusion Criteria

• •1. MRI of the brain shows evidence of central nervous system lymphoma; active primary central nervous system DLBL, unless central nervous system involvement has been effectively treated (i.e., participant is asymptomatic), and there has been more than a 4-week gap since local treatment.
• •2. Active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with central nervous system involvement.
• •3. History of or concurrent diagnosis of malignancies other than CD19+ malignancies.
• •4. Clinically significant heart disease or arrhythmias that cannot be controlled with medication.
• •5. Presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotics for treatment; uncomplicated urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
• •6. Positive for hepatitis B (HBsAg positive and HBV DNA \>1000 copies/mL) and hepatitis C (positive for HCV antibodies); syphilis or human immunodeficiency virus (HIV) infection.
• •7. Presence of any indwelling catheter or drainage tube (such as percutaneous nephrostomy, indwelling Foley catheter, bile drainage tube, or pleural/peritoneal/pericardial catheter); use of specialized central venous access devices like Port-A-Cath® or Hickman® catheters is allowed.
• •8. History of using any of the following medications:
• •1. Lenalidomide within 1 day before the apheresis.
• •2. Idelalisib (oral PI3Kδ inhibitor) within 2 days before the apheresis.
• •3. Short-acting targeted therapy (like tyrosine kinase inhibitors) within 72 hours before the apheresis.
• •4. Venetoclax (BCL-2 inhibitor) within 4 days before the apheresis.
• •5. Long-acting growth factors (like pegylated filgrastim) within 14 days before the apheresis, or short-acting growth factors or mobilization agents (like G-CSF/filgrastim, plerixafor) within 5 days before the apheresis.
• •6. Pharmacological doses of corticosteroids (\>5mg/day of prednisone or equivalent doses of other corticosteroids) or other immunosuppressive agents within 7 days before enrollment.
• •7. Radiation therapy within 14 days before enrollment.
• •8. Systemic cytotoxic drugs, including low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, methotrexate, or mercaptopurine, vincristine, etc.), within 14 days before enrollment. If bridging therapy is given after apheresis, there should be more than a 7-day gap between bridging therapy and CAR-T cell infusion.
• •9. Anti-PD1 or anti-PDL1 within 4 weeks prior to enrollment.
• •10. Live vaccines within 4 weeks prior to enrollment.
• •11. Donor lymphocyte infusion (DLI) within 4 weeks prior to enrollment.
• •12. Immune stimulation or immunosuppressive therapy (like interferon-α, interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or mycophenolate mofetil) within 4 weeks prior to enrollment.
• •13. Use of clofarabine or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.
• •9. Active graft-versus-host disease (GVHD) rated ≥2 on the CIBMTR acute GVHD grading system or requires systemic steroids at doses greater than physiological levels.
• •10. A history of autoimmune diseases in the past 2 years (like Crohn's disease, rheumatoid arthritis, or systemic lupus erythematosus) that has caused damage to end organs or requires systemic immunosuppression/systemic disease-modifying agents.
• •11. A history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant heart diseases within the 12 months prior to enrollment.
• •12. A history of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Schwachman-Diamond syndrome.
• •13. A history of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation in the 6 months before enrollment. Subjects need to be on preventive anticoagulant medication.
• •14. A history of other malignancies (except for non-melanoma skin cancer, in situ breast/cervical cancer, and other malignant tumors that have been effectively controlled without treatment in the past five years).
• •15. Use of other investigational medicinal products within 30 days prior to screening.
• •16. Pregnant or breastfeeding women of childbearing age. Women who have undergone surgical sterilization or are postmenopausal for at least 2 years are not considered of childbearing potential.
• •17. Male and female subjects unwilling to practice contraception from the time they agree to treatment until 12 months after completing the lymphodepleting chemotherapy or CAR-T infusion (whichever is longer).
• •18. Any medical activities that could interfere with the safety or efficacy evaluation of the study treatment.
• •19. In the judgment of the investigator, subjects are unlikely to complete all required study visits or procedures (including follow-ups) or to comply with the study participation requirements.