The goal of this clinical trial is to evaluate whether anti-CD19 CAR T-cell therapy can improve disease activity in adults with severe, treatment-resistant systemic sclerosis (SSc). The study will also assess the safety of this therapy and how CAR T-cells behave in the body.
The main questions are:
Does CAR T-cell therapy reduce skin thickening and other signs of SSc? What side effects occur after receiving CAR T-cells? How do CAR T-cells expand, persist, and affect B-cells and autoantibodies?
Participants will:
Undergo leukapheresis Receive short lymphodepleting chemotherapy Receive one infusion of anti-CD19 CAR T-cells Stay in the hospital for about 10 days Attend follow-up visits for 24 months with clinical exams, blood tests, and organ-function assessments
Optional skin or lymph-node biopsies may be performed in participants who consent to these procedures.
This study aims to provide early evidence on whether CAR T-cell therapy could become a promising treatment option for systemic sclerosis.
Severe and resistant to low dose steroids and at least 2 immunosuppressive treatment including csDMARDs (methotrexate, azathioprine, mycophenolate mofetil) and at least one bDMARDs (Tocilizumab)
Early onset (less than 2 years).
.mRSS >15 with at least one organ involvement (lung: FVC <80%, renal involvement, cardiac involvement, Creatinine < 1.5 mg/dl within 6 months).
mRSS <15 and lung fibrosis progression (FVC -10% DLCO -15% within 6 months)
Craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia or cerebrovascular hemorrhagic diseases
ECG showing prolonged QT interval or history of severe heart diseases or FEVG < 40%
Lung and / or heart severe dysfunction defined by CVF<50% and/or DLCO <40%
Pulmonary arterial hypertension defined by catheterism (mean AP > 25mmHg at rest or > 30mmHg after exercise, PAOP < 15mmHG)