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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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.
CHRU Lille
Lille, France
Montpellier University Hospital
Montpellier, France
APHP Necker
Paris, France
Chu Rouen
Rouen, France
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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 6 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day -14 to 24 months
Incidence of Scleroderma Renal Crisis
Incidence of clinically diagnosed scleroderma renal crisis
Time frame: Day -14 to 24 months
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