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)
Single group
CD19 CAR T Arm
Biological/VaccineAutologous anti-CD19 CAR-T cells are generated from the participant's leukapheresis product in a Good Manufacturing Practice (GMP)-certified facility using a lentiviral vector. Prior to infusion, participants will receive a short course of lymphodepleting chemotherapy. A single intravenous infusion of autologous anti-CD19 CAR-T cells will be administered on Day 0 at a target dose of 1 × 10⁶ CAR-T cells/kg. Participants will then be monitored in the hospital in accordance with standard post-CAR-T cell infusion procedures.
modified Rodnan skin score (mRSS)
Clinical response will be assessed through the modified Rodnan skin score (mRSS) which measures skin thickness on a scale of 0 to 3 at 17 anatomical sites (score range 0-51, higher scores indicating worse skin fibrosis)
Change in European Scleroderma Trial And Research (EUSTAR) activity index
Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \>18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \>1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \<70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease
Change in European Scleroderma Trial And Research (EUSTAR) activity index
Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \>18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \>1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \<70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease
Change in European Scleroderma Trial And Research (EUSTAR) activity index
Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \>18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \>1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \<70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease
Change in European Scleroderma Trial And Research (EUSTAR) activity index
Clinical response will also be assessed through the European Scleroderma Trial And Research (EUSTAR) disease activity (range 0-10, higher scores indicating greater disease activity) based on a weighted 10-point activity index : Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \>18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \>1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \<70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease
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