Clinical Study Evaluating the Safety and Efficacy of IC19 CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus

Inclusion Criteria

• •1. Subjects diagnosed with systemic lupus erythematosus who meet the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE;
• •2. Prior to screening, treatment with glucocorticoids (sufficient or shock therapy) combined with immunosuppressants (cyclophosphamide, mycophenolate mofetil, antimalarial drugs, azathioprine, methotrexate, leflunomide, tacrolimus, cyclosporine, etc.) and at least one biological agent (rituximab, belimumab, tacrolizumab, etc.) must have been received for at least 2 months, and the dosage must be stable for more than 2 weeks. The disease should still be active or recur after disease remission.
• •Oral corticosteroids need to meet the following conditions:
• •1. Prednisone (or equivalent) ≥ 7.5 mg/day and ≤ 60 mg/day;
• •2. When used in combination with immunosuppressants and/or biologics, there is no minimum daily dose requirement for glucocorticoids.
• •3\. When screening, the disease activity score (SLEDAI-2000) should be ≥ 8 points; 4. During the screening period, it meets the criteria of being positive for anti nuclear antibodies (ANAs), anti dsDNA antibodies, or anti Smith antibodies.
• •5\. Age range of 18-70 years old (including threshold), gender not limited; 6. Expected survival period of more than 3 months; 7. The functions of important organs meet the following requirements:
• •1. The bone marrow function needs to meet the following requirements: a. Neutrophil count ≥ 1 × 109/L; b. Platelets ≥ 50 × 109/L; c. Hemoglobin ≥ 60g/L;
• •2. Liver function: ALT ≤ 2.5 × ULN (upper limit of normal, ULN), AST ≤ 2.5 × ULN; TBIL ≤ 1.5 × ULN (for subjects with Gilbert syndrome, ALT and AST ≤ 5 × ULN, total bilirubin ≤ 3.0 × ULN);
• •3. Renal function: creatinine ≤ 1.5 × ULN or creatinine clearance rate (CrCl) ≥ 40 ml/min (Cockcroft/Gault formula);
• •4. Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN;
• •5. Cardiac function: Good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥ 50%;
• •6. Finger pulse oxygen saturation ≥ 92% in non oxygen state; 8. Women of childbearing age who have a negative blood pregnancy test before the start of the trial and agree to participate in the trial until the last time Visit individuals who have adopted effective contraceptive measures; Male participants with reproductive partners agree to take effective contraceptive measures during the trial period until the last follow-up; And not in the lactation period.
• •9\. The individual or legal guardian agrees to participate in this experiment and signs the informed consent form.
• •14. Hypertension with poor drug control (systolic blood pressure\>160mmHg and/or diastolic blood pressure\>90mmHg) or a history of any of the following cardiovascular diseases within 6 months prior to screening: long QTc syndrome or QTc interval\>480 ms; Complete left bundle branch block, grade II/III atrioventricular block; Severe and uncontrolled arrhythmias requiring medication treatment; History of chronic congestive heart failure and NYHA ≥ 3 (refer to Appendix 2) with a heart ejection fraction below 50% within the 6 months prior to screening; Heart valve disease with CTCAE ≥ 3 grade; Within the first 6 months of screening, there has been a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina, severe pericardial disease, or other clinically significant heart diseases;
• •15. History of symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months prior to the start of screening;
• •16. Other untreated malignant tumors within the past 5 years or simultaneously, excluding cervical cancer in situ, basal cell carcinoma of the skin, and ductal carcinoma in situ of the breast;
• •17. Infections (fungi, bacteria, viruses, or others) that require intravenous injection of antibiotics for control or are uncontrollable For simple urinary tract infections and bacterial pharyngitis, if the researchers evaluate that they can be controlled through treatment, they can be included in the study;
• •18. Individuals who are known to have allergic reactions, hypersensitivity reactions, intolerance, or contraindications to any ingredients of drugs that may be used in the study (including fludarabine, cyclophosphamide, tocilizumab, albumin), or who have previously experienced severe allergic reactions;
• •19. Have a history of alcohol or drug abuse in the past 24 weeks;
• •20. The researcher shall determine whether the subjects have any factors that affect compliance with the protocol, or are unwilling or unable to comply with the procedures required in the research protocol.