Anti-CD19-CAR-T Cells in Subjects With Relapsed/Refractory B Cell Malignancies

Exclusion Criteria39

• If patients meet any of the following conditions, they cannot participate in this trial:
• Central nervous system (CNS) involvement in ALL and clinically significant neurological changes (CNS-2 and CNS-3):
• CNS-3, defined as detectable tumor cells in cerebrospinal fluid (CSF) with ≥ 5 white blood cells (WBCs) /mm3.
• CNS-2, defined as detectable tumor cells in CSF with <5 WBCs /mm3. Note: Subjects with CNS-1 (no detectable tumor cells in CSF) or CNS-2 without evidence of clinically significant neurological changes are eligible for this study.
• CNS lymphoma confirmed by MRI; active CNS DLBL unless CNS involvement has been effectively treated (i.e., asymptomatic) and a local treatment interval of > 4 weeks prior to enrollment.
• Active CNS diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disorders, or any autoimmune diseases involving the central nervous system.
• Any malignancies other than CD19+ malignancies.
• Clinically significant heart disease or arrhythmias not controlled by medication.
• Ongoing or suspected fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotic therapy; simple urinary tract infections and simple bacterial pharyngitis are allowed.
• Hepatitis B (positive for hepatitis B surface antigen and hepatitis B DNA >1000 copies/mL) and hepatitis C (positive for hepatitis C antibodies); syphilis, human immunodeficiency virus (HIV) infection.
• Presence of any indwelling or drainage catheter (e.g., percutaneous nephrostomy, indwelling Foley catheter, biliary drainage catheter, pleural/peritoneal/pericardial drainage catheter); the use of dedicated central venous access devices such as Port-A-Cath® or Hickman® catheters is allowed.
• Prior use of the following:
• CD19-targeted therapy.
• Chlorambucil or bendamustine within 3 months before enrollment, or PEG-asparaginase within 3 weeks before enrollment.
• live vaccines within 4 weeks before enrollment.
• Donor lymphocyte infusions (DLI) within 4 weeks before enrollment.
• Medications for graft-versus-host disease (GVHD) treatment within 4 weeks before enrollment, such as calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, or siltuximab, or use of immunosuppressive antibodies (anti-CD20, anti-tumor necrosis factor, anti-interleukin 6, or anti-interleukin 6 receptor) within 4 weeks before enrollment.
• Immunostimulatory or immunosuppressive therapy within 4 weeks before enrollment, including interferon-α, interferon-β, IL-2, lenalidomide, efalizumab, alemtuzumab, tocilizumab, cyclosporine, or thalidomide.
• Anti-PD-1/anti-PD-L1 therapy within 4 weeks before enrollment.
• Systemic cytotoxic chemotherapy within 14 days before enrollment, including daily or weekly low-dose maintenance chemotherapy (e.g., cyclophosphamide, ifosfamide, bendamustine, chlorambucil, melphalan, or vincristine).
• Long-acting growth factors (e.g., pegfilgrastim) within 14 days before apheresis or short-acting growth factors within 5 days before apheresis or mobilization agents (e.g., filgrastim/pegfilgrastim, plerixafor) within 5 days before apheresis.
• Radiation therapy within 14 days before enrollment.
• Pharmacological doses of corticosteroids (>5 mg/day prednisone or equivalent) or other immunosuppressive drugs within 7 days before enrollment.
• Venetoclax (BCL-2 inhibitor) within 4 days before apheresis.
• Short-acting targeted therapy (e.g., tyrosine kinase inhibitors) within 72 hours before apheresis.
• Idelalisib (oral PI3Kδ inhibitor) within 2 days before apheresis.
• Lenalidomide within 1 day before enrollment.
• ≥ Grade 2 graft-versus-host disease (GVHD) per the CIBMTR grading system or requiring systemic corticosteroid treatment exceeding physiological doses.
• A history of autoimmune diseases in the past 2 years, such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, leading to end-organ damage or requiring systemic immunosuppression or disease-modifying agents.
• A history of heart attack, cardiac catheterization or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment.
• A history of genetic syndrome with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, Schwachman-Diamond syndrome, etc.
• Symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to be on prophylactic anticoagulation.
• A history of or currently having other malignant tumors (excluding skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have not been treated in the past five years but are effectively controlled).
• Use of other investigational medicinal products within 30 days before screening.
• Pregnant, planning to become pregnant, or breastfeeding in reproductive-aged women. Women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of reproductive potential.
• Male and female subjects unwilling to practice contraception from the time of agreeing to treatment until 12 months after completion of conditioning chemotherapy or CAR-T infusion.
• Any past medical history that may interfere with the safety of the study treatment or the evaluation of efficacy.
• Based on the investigator's judgment, subjects are unlikely to complete all the study visits or procedures required by the protocol.
• Previous use of any CAR-T cell product or other gene-modified T cell therapy.