Evaluation of the Safety and Efficacy of CD19 CAR T-Cell Therapy for the Treatment of Refractory Systemic Lupus Erythematosus: A Phase I Clinical Trial
The goal of this Phase I clinical trial is to evaluate the safety and tolerability of autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy in adults with refractory systemic lupus erythematosus who have demonstrated inadequate response to standard-of-care immunosuppressive treatments. The primary questions this study aims to address are: What is the incidence, nature, and severity of treatment-emergent adverse events following CD19 CAR-T cell infusion? Is administration of CD19 CAR-T cell therapy feasible and tolerable in patients with refractory systemic lupus erythematosus? This study is conducted as a single-arm trial without a comparison group. Participants will: Undergo leukapheresis for collection of autologous peripheral blood mononuclear cells Receive a protocol-defined lymphodepleting chemotherapy regimen prior to CAR-T cell infusion Receive a single intravenous infusion of approximately 1.0 × 10⁶ CD19 CAR-T cells per kilogram of body weight Undergo scheduled clinical evaluations, laboratory testing, and longitudinal follow-up to assess safety, tolerability, and clinical parameters
• Age 16 to 55 years, male or female
• Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria with a total score ≥ 10
• SLEDAI-2K score ≥ 8 at screening (with at least 4 points derived from laboratory parameters; excluding points attributable to central nervous system involvement)
• Positive antinuclear antibody (ANA ≥ 1:80) OR positive anti-dsDNA OR positive anti-Sm antibody at screening or documented in medical history
∙ Refractory systemic lupus erythematosus or refractory lupus nephritis defined as one of the following:
∙ Refractory SLE:
∙ \- Failure to achieve adequate response, partial response, or stable disease control after ≥ 6 months of standard-of-care therapy (documented compliance). Standard therapy includes corticosteroids plus hydroxychloroquine and at least two of the following: calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, or B-cell-targeted therapy (e.g., rituximab, belimumab).
∙ Refractory Lupus Nephritis:
• Persistent active lupus nephritis after two induction regimens, including intravenous cyclophosphamide and mycophenolate mofetil administered for ≥ 6 months (with or without calcineurin inhibitors, rituximab, or belimumab), AND:
• Histopathologic confirmation of Class III or Class IV lupus nephritis, with or without Class V (ISN/RPS 2003 classification); isolated Class V is excluded
• Proteinuria \> 1 g/24 hours OR urine protein-to-creatinine ratio \> 1 mg/mg
• Adequate organ function:
‣ ALT ≤ 5 × upper limit of normal; total bilirubin ≤ 34 μmol/L (≤ 2.0 mg/dL)
⁃ Pulmonary function: FVC ≥ 60% predicted OR FEV1 ≥ 60% predicted
⁃ Cardiac function: LVEF ≥ 50%, no uncontrolled arrhythmia, no intracardiac thrombus, no heart failure
• Adequate hematologic parameters:
‣ Absolute neutrophil count ≥ 0.8 × 10⁹/L (without growth factor support)
⁃ Absolute lymphocyte count ≥ 0.3 × 10⁹/L
⁃ Platelet count ≥ 50 × 10⁹/L
⁃ Hemoglobin ≥ 80 g/L (≥ 8.0 g/dL)
• Ability to provide written informed consent
• Agreement to use effective contraception during the study period (for participants of reproductive potential)