SCLEROCAR: A Phase IIa Trial Evaluating the Efficacy of Anti-CD19 Chimeric Antigen Receptor Engineered T-Cells in Patients With Systemic Sclerosis (SSc) Resistant to Immunosuppressive Drugs
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.
• Adequate organ functions assessed:
‣ serum Creatinine clearance \> 40ml/mi
⁃ adequate bone marrow function (Hemoglobin ≥9g/dL ; PMN ≥ 1 G/L ; Platelets ≥ 100 G/L)
⁃ Alanine aminotransferase (ALT) ≤ 3 x ULN and total bilirubin \< 2.0 mg/dL (34 μmol/L) (or \< 3.0 mg/dL \[51 μmol/L\] for subjects with Gilbert's syndrome)
⁃ Adequate respiratory function: no dyspnea or grade I dyspnea (Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0) and oxygen saturation \>/= 92% on room air
• Adequate venous access for apheresis
• Leucapheresis : a wash-out period of 6 weeks for conventional immunosuppressants (i.e. methotrexate, mycophenolate mofetil)
• Leucapheresis : at least 12 weeks after biotherapy (i.e. tocilizumab, 6 months for rituximab),