A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Study Overview
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Brief Summary
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A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Detailed Description
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Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells. This fully reflects the application prospects of CAR-T cells in autoimmune diseases. Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory scleroderma

Official Title
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A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Conditions
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Scleroderma, Autoimmune Diseases

Intervention / Treatment
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* Biological: Assigned Interventions CD19/BCMA CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scleroderma with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment Estimated survival time> 12 weeks; Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Patients with HIV infection; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment of Scleroderma<br>Experimental：Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject. | Biological: Assigned Interventions CD19/BCMA CAR T-cells<br>* Drug: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Name: CD19/BCMA CAR T-cells injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD19/BCMA CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 90 days after CD19/BCMA CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CAR-T cells | In peripheral blood | From admission to the end of the follow-up, up to 2 years | 
| Objective Response Rate, ORR | Proportion of subjects with complete or partial remission | In 3 months of CD19/BCMA CAR-T cell infusion | 
| Disease control rate, DCR | The percentage of patients with remission and stable disease after treatment in the total evaluable cases. | From Day 28 CD19/BCMA CAR-T infusion up to 2 years | 
| Duration of remission, DOR | The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-T cells infusion | 
| Progression-free survival, PFS | The time from cell reinfusion to the first assessment of disease progression or death from any cause | 24 months post CD19/BCMA CAR-Tcells infusion | 
| Overall survival, OS | The time from the cell reinfusion to death due to any cause | From CD19/BCMA CAR-T infusion to death，up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scleroderma, CD19 CAR T-cell therapy, BCMA CAR T-cell therapy