Open-Label, Non-Randomized, Single-Arm, Phase 1/2 Study of Anti-CD19 Chimeric Antigen Receptor T Cells for Refractory Systemic Lupus Erythematosus
The goal of this study is to evaluate the safety and efficacy of CD19 CAR T cells in the treatment of Systemic lupus erythematosus (SLE).
• Male or female, aged 3-65 years.
• Have a diagnosis of SLE and meet the classification criteria of 2019 European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
• Positive antinuclear antibody (ANA): ANA at a titer of ≥ 1:80 on Hep-2 cells or equivalent positive test (ever) and/or a positive anti-dsDNA serum antibody test (based on ELISA assay, ≥ 30 IU/mL).
• Refractory SLE and/or refractory lupus nephritis (LN):
• • 4.1 Refractory SLE 4.1.1 Patients received at least 7.5 mg/kg/day of prednisolone to maintain low disease activity or the SLEDAI 2K score ≥8.
‣ 1.2 Routine treatment is ineffective or the disease relapses after remission. Definition of routine treatment: use glucocorticoid (more than 1mg/kg/d) and cyclophosphamide for 6 months; and any of the following immunomodulatory drugs for more than 3 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents such as rituximab, belizumab, or telitacicept;
• • 4.2 Refractory LN 4.2.1 Diagnosis of SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR), Biopsy-proven LN class III, IVa \[excluding III (C), IV-S (C) and IV-G (C)\] or, class V lupus nephritis combined with class III or IV, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, see Appendix 3. Biopsy must be performed within 6 months before or during screening.
‣ 2.2 Refractory lupus nephritis is defined as no induced remission to treatment regimens containing at least one immunosuppressant (including glucocorticoids, CTX, tacrolimus, MME, and cyclosporine) after 3 to 6 months, accompanied by no reduction (or worsening) of proteinuria or persistent antibody positives.
• CD19+ on B cells and continuous withdrawal of the immunosuppressive drugs for more than 1 week.
• The blood routine lymphocyte count of the subjects is \> 1 × 109/L, and there is no cell collection contraindication.
• No severe allergy.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2.
• Patients are expected to live for at least 90 days.
⁃ Subjects and/or their guardian must understand and sign the informed consent.