Phase IIa Trial of Anti-CD19 CAR T-Cells in Systemic Sclerosis Resistant to Immunosuppressive Therapy (SCLEROCAR)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Scleroderma, Systemic
• Intervention / Treatment: Biological: CD19 CAR T Arm

Detailed Description

Systemic sclerosis (SSc) is a rare and severe autoimmune disease characterized by fibrosis of the skin and multiple organs, vasculopathy, and immune dysregulation. Many patients continue to experience active and progressive disease despite conventional immunosuppressive treatments, including disease modifying antirheumatic drugs (DMARDs) and biologics. Therapeutic options remain limited, and there is a significant unmet medical need for innovative approaches targeting the underlying mechanisms of the disease.

Recent preliminary experience from studies conducted in autoimmune diseases-such as lupus, myositis, and systemic sclerosis-suggests that autologous anti CD19 CAR T cell therapy may help reduce disease activity. Reported observations include transient B cell depletion, decreases in autoantibody levels, and improvements in joint, pulmonary, and cardiac manifestations. These early results support further evaluation of CAR T cell therapy in systemic sclerosis in a structured clinical trial setting.

This Phase IIa, multicenter, single-arm study is designed to evaluate the feasibility and safety of autologous anti-CD19 CAR-T cell therapy in adults with active systemic sclerosis who are resistant to immunosuppressive treatments. The study also aims to generate early clinical and biological data to assess the potential value of this therapeutic strategy in this population.

Eligible participants will undergo leukapheresis for T-cell collection. Following standard manufacturing of autologous anti-CD19 CAR-T cells in a GMP (Good Manufacturing Practice)-certified facility, participants will receive a short course of lymphodepleting chemotherapy, followed by a single intravenous infusion of CAR-T cells. They will remain hospitalized for intensive monitoring during the early post-infusion period, in accordance with established procedures for CAR-T cell therapies. Participants with known hypersensitivity to drugs required for treatment-related toxicity are excluded, as specified in the protocol.

After discharge from the hospital, participants will have follow-up visits for up to 24 months. These visits will include clinical and biological assessments as well as appropriate imaging tests to monitor disease activity, treatment safety, and overall health status. Biological samples will also be collected at specific times for centralized analysis.

The study incorporates exploratory immunological and translational research components. These may include monitoring circulating CAR T cells, characterizing immune cell subsets, and evaluating selected biomarkers. Optional skin and lymph node biopsies may be performed in consenting participants to analyze immune cell phenotypes and tissue level changes associated with treatment. Additional exploratory analyses may assess the spatial organization and distribution of immune cells within tissue samples, as described in the study protocol.

Overall, the study aims to provide early data on the use of anti CD19 CAR T cell therapy in systemic sclerosis, including feasibility, safety, and biological signals of activity. The results are expected to contribute to the development of innovative cell based therapeutic strategies for this severe autoimmune disease.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Charlotte KAAN; Phone Number: 33 04 67 33 48 53; Email: c-kaan@chu-montpellier.fr

Study Locations

• France
  • Lille, France
    • CHRU Lille
    • Contact: David LAUNAY, Pr; Email: david.launay@chu-lille.fr
    • Sub-Investigator: Ibrahim YAKOUB-AGHA, Pr
  • Montpellier, France
    • Montpellier University Hospital
    • Contact: Charlotte KAAN
    • Contact: Christian JORGENSEN, Pr; Phone Number: 33 04 67 33 48 53; Email: c-kaan@chu-montpellier.fr
  • Paris, France
    • APHP Necker
    • Contact: Yannick ALLANORE, Pr; Email: yannick.allanore@me.com
    • Sub-Investigator: Olivier HERMINE, Pr
  • Rouen, France
    • CHU Rouen
    • Contact: Olivier BOYER, PUPH; Email: olivier.boyer@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Pre-Inclusion criteria:

1. Diagnosis of systemic sclerosis according to ACR/EULAR 2013 classification (15).we include in the critera the fulfilling of 2013 EULAR/ACR criteria and specify disease duration (less than 2 years), score/clinical evidence for active disease :
2. 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)
3. Early onset (less than 2 years).

4. Severity & progression of disease be defined by :

   1. .mRSS >15 with at least one organ involvement (lung: FVC <80%, renal involvement, cardiac involvement, Creatinine < 1.5 mg/dl within 6 months).
   2. mRSS <15 and lung fibrosis progression (FVC -10% DLCO -15% within 6 months)
5. patients with active disease (as defined by EUSTAR ≥2.5) and to patients with a worsening disease despite 6 months of at least 2 immunosuppressive treatments including one DMARDs (methotrexate, azathioprine, mycophenolate mofetil), and one biological DMARD rituximab or tocilizumab.
6. Estimated survival time > 24 weeks
7. Age: ≥18 ≤64 years old voluntary to participate in the study and sign the informed consent

8. Adequate organ functions assessed :

   1. serum Creatinine clearance > 40ml/mi
   2. adequate bone marrow function (Hemoglobin ≥9g/dL ; PMN ≥ 1 G/L ; Platelets ≥ 100 G/L)
   3. 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)
   4. 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
9. Highly effective contraception methods

Inclusion criteria:

1. Adequate organ functions assessed:

   1. serum Creatinine clearance > 40ml/mi
   2. adequate bone marrow function (Hemoglobin ≥9g/dL ; PMN ≥ 1 G/L ; Platelets ≥ 100 G/L)
   3. 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)
   4. 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
2. Adequate venous access for apheresis
3. Leucapheresis : a wash-out period of 6 weeks for conventional immunosuppressants (i.e. methotrexate, mycophenolate mofetil)
4. Leucapheresis : at least 12 weeks after biotherapy (i.e. tocilizumab, 6 months for rituximab),

Exclusion Criteria:

1. Craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia or cerebrovascular hemorrhagic diseases
2. ECG showing prolonged QT interval or history of severe heart diseases or FEVG < 40%
3. Lung and / or heart severe dysfunction defined by CVF<50% and/or DLCO <40%
4. Pulmonary arterial hypertension defined by catheterism (mean AP > 25mmHg at rest or > 30mmHg after exercise, PAOP < 15mmHG)
5. Clinically significant active, opportunistic, chronic or recurrent infection (including but not limited to: hepatitis B or C virus or HIV) or covid-19 < 1 months including active or latent tuberculosis (TB) infection
6. Contra indication for autologous hematopoietic stem cell transplantation (AHSCT ) or relapsing at least one year after AHSCT
7. Active hematological or solid neoplasm
8. Concurrent therapy with systemic steroids (>10 mg/d prednisone equivalent) within 2 weeks prior to inclusion, except inhaled steroids
9. Methylprednisolone or prednisone (maximum dose 20 mg) instead of immunosuppressive agents
10. T cell targeting drugs (e.g. mycophenolate mofetil, azathioprine, calcineurin inhibitors) within 6 weeks prior to leukapheresis
11. Previous adoptive T cell therapy or any gene therapy including CAR T cell therapy
12. Live vaccines within 6 weeks prior to leukapheresis
13. Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative chemotherapy or rescue medication/salvage therapies for treatment related toxicities
14. patients without social security coverage;
15. patients under guardianship;
16. Male or female patients seeking to conceive a child
17. Women of childbearing potential unless they are using a highly effective method of contraception starting from the time of enrolment and for at least 12 months following LD chemotherapy and until clearance of CAR-T cells, and sexually active male participants unwilling to use a condom. Female partners of sexually active male participants must be on a highly effective form of birth control from the time of enrolment and for at least 12 months following LD chemotherapy and until clearance of CAR-T cells.
18. pregnant or breastfeeding women;
19. patients with advanced cognitive disorders or any other cause preventing their informed consent;
20. active, clinically significant CNS pathology : If signs or symptoms exist which present diagnostic uncertainty, neurologist consultation will be obtained to confirm the diagnosis of any neurological condition
21. any comorbidity, whatever it may be, which may, in the opinion of the investigator, place the patient at additional risk or interfere with the monitoring of the study.
22. Concurrent participation in any other interventional trial and Contraindication to the lymphodepleting chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CD19 CAR T Arm; Participants assigned to this arm will undergo leukapheresis and receive a lymphodepleting chemotherapy regimen, followed by a single intravenous infusion of autologous anti-CD19 CAR T-cells on Day 0. All participants enrolled in the study are included in this single experimental arm

Biological: CD19 CAR T Arm; Autologous 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	6 Months
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	From 3 months to 1 month before CAR-T cell infusion
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	1 month before CAR-T cell infusion
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	Day 0 (CAR-T cell infusion)
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	Day 28 after CAR-T cell infusion
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	3 Months
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	6 Months
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	12 Months
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	24 Months
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)	From 3 months to 1 month before CAR-T infusion
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)	1 month before CAR-T infusion
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)	Day 0 (CAR-T infusion)
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)	Day 28 after infusion
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)	2 Months
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)	3 Months
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)	12 months
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)	24 months
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	From 3 months to 1 month before CAR-T infusion
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	1 month before CAR-T infusion
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	Day 0 (CAR-T infusion)
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	Day 28 after infusion
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	2 Months
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	3 Months
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	6 Months
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	12 Months
Change in Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS)	Clinical response will be assessed using the revised Combined Response Index in diffuse cutaneous Systemic Sclerosis (rCRISS). The rCRISS is a 2-step composite score: Step 1: Patients are considered not improved if any of the following occur: scleroderma renal crisis, significant FVC decline (≥15% or FVC% <80%), new left ventricular failure (LVEF ≤45%), new pulmonary arterial hypertension requiring treatment, gastrointestinal dysmotility requiring nutritional support, or digital ischemia requiring treatment or hospitalization. Step 2: For other patients, improvement is defined as ≥40% improvement in at least 3 of 5 measures: mRSS, HAQ-DI, patient global assessment, clinician global assessment, and percent predicted FVC. Additional assessments include spirometry (FVC, DLCO), thoracic CT fibrosis, echocardiography (LVEF, global longitudinal strain), cardiac MRI, and SHAQ score	24 Months
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	From 3 months to 1 month before CAR-T infusion
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	1 month before CAR-T infusion
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	3 Months
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	6 Months
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	12 Months
Change in the lung capacity FVC (forced vital capacity)	To assess the impact of the treatment on pulmonary function, FVC will be assessed during functionnal exploration test lab and we will evaluate the improvement in FVC over time	24 Months
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	From 3 months to 1 month before CAR-T infusion
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	1 month before CAR-T infusion
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	3 Months
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	6 Months
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	12 Months
Change in DLCO (diffusing capacity of the lung for carbon monoxide)	The efficacy of the treatment on pulmonary function will also be analyzed by monitoring changes in DLCO (diffusing capacity of the lung for carbon monoxide), quantifiy during functionnal exploration test lab	24 Months
Extent of fibrosis on pulmonary CT (Computed Tomography)	Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb)	From 3 months to 1 month before CAR-T infusion
Extent of fibrosis on pulmonary CT(Computed Tomography)	Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb)	3 Months
Extent of fibrosis on pulmonary CT(Computed Tomography)	Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb)	12 Months
Extent of fibrosis on pulmonary CT(Computed Tomography)	Pulmonary response will be also assessment by CT scan and expressed as percentage of parenchyma affected. The type of parenchymal involvement willbe specified (ground glass, honeycomb)	24 Months
Change in cardiac ejection fraction and global longitudinal strain	A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS).	From 3 months to 1 month before CAR-T infusion
Change in cardiac ejection fraction and global longitudinal strain	A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS).	3 Months
Change in cardiac ejection fraction and global longitudinal strain	A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS).	12 Months
Change in cardiac ejection fraction and global longitudinal strain	A transthoracic cardiac ultrasound will be performed regularly to assess the effect of treatment on the left ventricular ejection fraction, as well as the global longitudinal strain (GLS).	24 Months
Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal	A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension	From 3 months to 1 month before CAR-T infusion
Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal	A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension	12 Months
Cardiomyopathy, change in cardiac MRI (Magnetic Resonance Imaging) signal	A cardiac MRI (Magnetic Resonance Imaging) will be performed at baseline and at follow-up visit to evaluate the effect of treatment on T1 and T2 mapping, late gadolinium enhancement (LGE), extracellular volume ( ECV) mapping and indirect indicators of pulmonary hypertension	24 Months
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	Day 0 (CAR-T infusion)
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	Day 28 after CAR-T cell infusion
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	3 Months
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	6 Months
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	12 Months
Change in scleroderma-adapted Scleroderma Health Assessment Questionnaire (SHAQ) score	Clinical response will be assessed using SHAQ : the patient will complete a self-assessment questionnaire on their health status during systemic sclerosis (SSc) and we will compare the scores at each stage	24 Months
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	Day 0 (CAR-T cell infusion)
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	Day 28 after CAR-T cell infusion
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	3 Months
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	6 Months
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	12 Months
Change in Health Assessment Questionnaire Disability Index HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a quantitative tool used to measure health related quality of life assessments related to SSc ; Clinical response will be assessed using HAQ-DI and we will compare the scores at each stage	24 Months
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	Day 0 (CAR-T cell infusion)
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	Day 28 after CAR-T cell infusion
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	3 Months
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	6 Months
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	12 Months
Change in Health Assessment Questionnaire Cochin Hand score	Clinical response will also be assessed using the Cochin Hand Function Scale, a validated tool that quantifies disability resulting from hand functional impairment.	24 Months
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the SF36 self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	Day 0 (CAR-T cell infusion)
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	Day 28 after CAR-T cell infusion
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	3 Months
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	6 Months
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	12 Months
Change in quality of life Questionnaire SF-36	Clinical response will also be assessed using the SF36 score collected at each time point through the 36-Item Short Form Survey (SF-36) self-assessment questionnaire, which evaluates the patient's quality of life across eight domains, including physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health	24 Months
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	Day 0 (CAR-T cell infusion)
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	Day 28 after CAR-T cell infusion
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	3 Months
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	6 Months
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	12 Months
Change in the university of California Los Angeles scleroderma clinical trials consortium gastrointestinal tract (ULCA-SCTC GIT) score	to evaluate disease response on to systemic sclerosis associated gastrointestinal tract symptoms severity and its impact on patients' well-being, we will compare ULCA-SCTC GIT Score, which is a self-administered questionnaire completed at each time point	24 Months
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	From 3 months to 1 month before CAR-T cell infusion
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	1 month before CAR-T cell infusion
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	Day 0 (CAR-T cell infusion)
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	Day 28 after CAR-T cell infusion
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	3 Months
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	6 Months
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	12 Months
Change in Malnutrition Universal Screening Tool (MUST) score	We will also assess the effect of treatment on digestive impairment in scleroderma patient, as well as their risk of malnutrition, using the MUST score. This evaluation includes measuring the percentage of weight loss over the previous 3 to 6 months, calculating body mass index, and determining whether the patient has been seriously ill and experienced a period of more than 5 days without nutritional intake	24 Months
Anti-antibody titers	Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration	From 3 months to 1 month before CAR-T cell infusion
Anti-antibody titers	Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration	Day 28 after CAR-T cell infusion
Anti-antibody titers	Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration	6 Months
Anti-antibody titers	Measurement of antinuclear antibodies (ANA), anti-centromere, anti-DNA, anti-Topoisomerase, and TRAK antibody titers following CAR T anti-CD19 cell administration	12 Months
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 0 (CAR-T cell infusion)
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 4 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 7 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 10 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 14 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 21 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	Day 28 after CAR-T cell infusion
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	3 Months
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	6 Months
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	12 Months
CAR T cell counts	Quantification of CAR T cells using flow cytometry and qPCR to assess expansion and persistence after CAR T anti-CD19 infusion	24 Months
Immunophenotyping of B, T, and NK cells subsets	Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion	Day -14 (14 days before CAR-T infusion)
Immunophenotyping of B, T, and NK cells subsets	Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion	Day 28 after CAR-T cell infusion
Immunophenotyping of B, T, and NK cells subsets	Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion	3 Months
Immunophenotyping of B, T, and NK cells subsets	Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion	6 Months
Immunophenotyping of B, T, and NK cells subsets	Immunophenotyping of B cells, T cells, NK cells, and immune subpopulations to evaluate immune reconstitution following CAR T infusion	12 Months
B-cell receptor (BCR) repertoire analysis	BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration	Day -14 (14 days before CAR-T infusion)
B-cell receptor (BCR) repertoire analysis	BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration	6 Months
B-cell receptor (BCR) repertoire analysis	BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration	12 Months
B-cell receptor (BCR) repertoire analysis	BCR repertoire analysis performed on B cells from Systemic Sclerosis (SSc) patients. Assessment occurs at Month 6 if B-cell percentage is >50% of baseline; otherwise at Month 12 after CAR T anti-CD19 administration	24 Months
Skin biopsies for single-cell phenotyping	Skin biopsies (for patients who have given their consent) performed at baseline for single-cell phenotyping analyses.	From 3 months to 1 month before CAR-T infusion
Skin biopsies for single-cell phenotyping	Skin biopsies (for patients who have given their consent) performed at M3 for single-cell phenotyping analyses.	3 Months
lymph node biopsies for single-cell phenotyping	lymph node biopsies (for patients who have given their consent) performed at Month 3 for single-cell phenotyping analyses.	3 Months
Incidence rate of adverse events	Incidence rate of adverse events graded according to the Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and classified following the American Society of Clinical Oncology (ASCO) guidelines	Day -14 to 24 months
Incidence of Cytokine Release Syndrome (CRS)	Incidence and severity of Cytokine Release Syndrome (CRS), graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system.	Day -14 to 24 months
Incidence of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)	Incidence and severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system	Day -14 to 24 months
Incidence of Cytopenias	Incidence and severity of cytopenias, graded according to the consensus grading system of the European Hematology Association (EHA) and the European Society for Blood and Marrow Transplantation (EBMT) consensus grading system	Day -14 to 24 months
Incidence of Infections	Incidence and severity of infections, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Day -14 to 24 months
Incidence of Cardiac Events	Incidence and severity of cardiac adverse events, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Day -14 to 24 months
Incidence of Acute Kidney Injury	Incidence and severity of acute kidney injury, graded according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Day -14 to 24 months
Incidence of Scleroderma Renal Crisis	Incidence of clinically diagnosed scleroderma renal crisis	Day -14 to 24 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Christian Jorgensen, PUPH, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Anti-CD19 CAR T-cells; Autologous CAR T-cell therapy
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic
• Other Study ID Numbers: RECHMPL24_0438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No