JWCAR239 in Patients With B Cell Non-Hodgkin Lymphoma

Exclusion Criteria

• •1. Lymphoma involving the central nervous system (CNS).
• •2. EBV-positive DLBCL or Richter transformation of chronic lymphocytic leukemia.
• •3. History of other malignant tumors with complete remission for less than 2 years, or current presence of other malignant tumors (exceptions to the 2-year restriction include: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, treated localized prostate cancer, biopsy-confirmed cervical in situ carcinoma, or cervical smears showing squamous intraepithelial lesions, or completely resected tumors with low recurrence potential as assessed by the investigator).
• •4. At screening, the subject has:
• •Active hepatitis B or C (subjects with HBV DNA or HCV RNA below the lower limit of the central reference value by PCR may be enrolled). For occult or prior HBV-infected subjects, prophylactic antiviral therapy and regular monitoring of HBV-DNA are required.
• •Human immunodeficiency virus (HIV) infection or syphilis infection.
• •5. Acute deep vein thrombosis (DVT) (tumor thrombus or thrombus) or pulmonary embolism (PE) within 3 months prior to informed consent signing.
• •6. Receiving anticoagulant therapy for acute DVT or PE within 3 months prior to informed consent signing (prophylactic treatment ).
• •7. Uncontrolled systemic fungal, bacterial, viral, or other infections.
• •8. Acute or chronic graft-versus-host disease (GvHD).
• •9. History of any of the following cardiovascular diseases within the past 6 months: New York Heart Association (NYHA) Class III or IV heart failure, coronary angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart diseases.
• •10. Clinically significant CNS disease or symptoms at screening or within the past 6 months, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric disorders.
• •11. Pregnant or lactating women. Females of childbearing potential must have a negative serum pregnancy test within 48 hours before starting lymphodepletion chemotherapy.
• •12. Use of any of the following drugs or treatments within the specified time before leukapheresis:
• •Alemtuzumab within 6 months before leukapheresis. Bendamustine within 6 months before leukapheresis. Cladribine within 3 months before leukapheresis. Fludarabine within 3 months before leukapheresis. Anti-CD20 monoclonal antibodies within 7 days before leukapheresis. Venetoclax within 4 days before leukapheresis. Idelalisib within 2 days before leukapheresis. Lenalidomide within 1 day before leukapheresis. Pharmacological doses of corticosteroids (defined as prednisone \>5 mg/day or equivalent) within 7 days before leukapheresis or within 72 hours before JWCAR239 injection. Physiological replacement, topical, and inhaled steroids are permitted.
• •Chemotherapy (e.g., vincristine, rituximab, cyclophosphamide) required to control the disease after leukapheresis must have been discontinued ≥7 days before lymphodepletion chemotherapy.
• •Administration of non-lymphocyte-toxic cytotoxic chemotherapy within 1 week before leukapheresis. Enrollment is permitted if the oral chemotherapy has undergone at least 3 half-lives before leukapheresis.
• •Receipt of lymphocyte-toxic chemotherapy (e.g., cyclophosphamide, ifosfamide, chlorambucil, or melphalan) within 2 weeks before leukapheresis.
• •Use of investigational drugs within 4 weeks before leukapheresis. However, enrollment is permitted if the investigational treatment was ineffective or caused disease progression, and at least 3 half-lives have elapsed before leukapheresis.
• •Treatment with immunosuppressive agents (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutic drugs, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R) within 4 weeks before leukapheresis and JWCAR239 injection.
• •Receipt of donor lymphocyte infusion (DLI) within 6 weeks before JWCAR239 injection.
• •Radiation therapy involving large bone marrow areas (e.g., sternum or pelvis) within 6 weeks before leukapheresis. Subjects are eligible only if the disease progresses at the radiation site or PET-positive lesions exist in non-irradiated areas. If PET-positive lesions exist in non-irradiated areas, radiation therapy to a single lesion is permitted within 2 weeks before leukapheresis.
• •13. Any other significant disease, abnormality, or condition that, in the investigator's judgment, renders the subject unsuitable for participation in the study or places the subject at risk. Any factors affecting compliance with the protocol, including uncontrollable medical, psychological, family, sociological, or geographical factors; or unwillingness or inability to adhere to the procedures required by the study protocol.
• •14. Prior allogeneic hematopoietic stem cell transplantation.
• •15. Prior treatment with CAR+ T cells or other genetically modified T cells.