CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus

Summary

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

Eligibility

Inclusion Criteria:

* 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)

Exclusion Criteria:

* History of significant neurologic disorders (e.g., traumatic brain injury, seizure disorder, hemorrhagic conditions, impaired consciousness)
* Significant cardiovascular disease within 3 months prior to screening (e.g., uncontrolled hypertension, NYHA Class III-IV heart failure, severe arrhythmia, unstable angina, myocardial infarction)
* Prior kidney transplantation
* Severe asthma requiring long-term treatment or respiratory failure
* Severe hemolytic anemia requiring transfusion at intervals ≤ 7 days
* Active viral infections (e.g., hepatitis B or C, HIV, tuberculosis, malaria, syphilis, CMV, EBV) or other life-threatening infectious diseases
* Active bacterial infection confirmed by clinical evaluation, imaging, or laboratory testing
* Use of the following prior to leukapheresis:

  * Anti-CD20 therapy, cyclophosphamide, live or attenuated vaccines within 1 month
  * Systemic corticosteroids \> 10 mg/day (prednisone equivalent), T-cell-targeted therapy (e.g., mycophenolate mofetil, calcineurin inhibitors), immunosuppressive agents, or antimalarial agents within 7 days
  * Prior anti-CD19 therapy
  * Prior T-cell-based cellular therapy or gene therapy, including CAR-T therapy
* Current or prior malignancy
* Known hypersensitivity to study-related agents
* Pregnant or breastfeeding women
* Active antiphospholipid syndrome (stable antiphospholipid antibody positivity without active APS is permitted)
* Participation in another clinical trial at the time of screening
* Any condition that, in the investigator's judgment, would interfere with protocol compliance or study participation

Conditions2

Interventions1

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