Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease

Overview

This is a single arm study to evaluate the efficacy and safety of CD19 targeted CAR-T cells therapy for patients with Refractory Autoimmune Disease

Description

the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. Otherwise, some studies have shown that the use of CD19-targeted CAR-T therapy in refractory SLE can improve the autoimmune symptoms of patients, and at the same time, immunosuppressants and hormones can be stopped to maintain long-term autoimmune indicators normal.To verify the safety and efficacy, the investigators launch such a clinical trial using CD19 targeted CAR-T cells for patients with Refractory Autoimmune Disease.

Eligibility

Inclusion Criteria:

1. ≥18 years old, male or female;
2. diagnosed with one of the following diseases:
   • Systemic Lupus Erythematosus (SLE), EULAR/ACR 2019 standard;
   • Sjogren's Syndrome (SS), 2016 ACR/EULAR standard;
   • Systemic Scleroderma (SSc), 2013 ACR/EULAR Standards;
   • Dermatomyositis (DM), 2017 EULAR/ACR classification standard + one positive myositis specific antibody (Jo-1, Zo, EJ, PL-7, KS, OJ, PL-12, YRS, Anti-NXP-2, Anti-TIF1g, Anti-Mi-2, Anti-SAE, Anti-MDA-5, Anti-SRP, Anti-HMGCR);
   • Anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV), including granulomatosis with polyangiitis (GPA), or microscopic vasculitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA), 2022 ACR/EULAR standard.
3. Disease activity meets the following requirements:
   • SLEDAI score ≥8 for SLE patients;
   • For SS patients, ESSDAI≥14 points;
   • For patients with SSc, mRSS score in the range of 10-35 (including the boundary value) with interstitial pneumonia (ILD);
   • Patients with DM who have been diagnosed for at least 1 year and meet the following conditions:
     1. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;

                  2, muscle biopsy pathology or muscle nuclear magnetic evidence of active
                  inflammation;
                  3. Bilateral manual muscle strength test (MMT-8) is less than 125/150, and at
                  least 2 additional Core set measures (CSM) meet the following criteria: Patient
                  score, 10 cm visual analogue scale (VAS) no less than 2.0 cm; b. Physician score,
                  no less than 2.0 cm on the 10 cm VAS scale; c. Health Assessment Questionnaire
                  (HAQ) disability index (Appendix 10) of not less than 0.25; d. Elevation of at
                  least one muscular enzyme (including creatine kinase (CK), aldolase, lactate
                  dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate
                  aminotransferase (AST)), with a minimum level of 1.3× the upper limit of normal;
                  e. Disease activity score of extramuscular organs, no less than 1.0 cm on the 10
                  cm VAS scale (this VAS is the physician's comprehensive assessment of myositis
                  disease Activity Assessment Tool (MDAAT) based on the general condition, skin,
                  bone, gastrointestinal, lung, and heart scale activity score);
               -  For ANCA-AAV patients, the BVAS score was ≥15.
          4. ECOG 0~1 score;
          5. The functions of important organs are basically normal:
               -  Hematology: hemoglobin ≥60g/L, platelet count ≥30×109/L;
               -  Cardiac function: Left ventricular ejection fraction (LVEF) ≥55%, no obvious
                  abnormality in electrocardiogram;
               -  Renal function: eGFR≥30ML/min/1.73m2;
               -  Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0 ULN;
               -  Lung function: DLCO≥40% predicted value; FVC≥50% expected value;
               -  Have criteria for simple or intravenous blood collection, and no other
                  contraindications for cell collection;
          6. The subject of childbearing age has a negative urine pregnancy test result and agrees
             to take effective contraceptive measures during the test period until 1 year after the
             infusion;
          7. The patient or his/her guardian agrees to participate in the clinical trial and signs
             the informed consent, indicating that he/she understands the purpose and procedure of
             the clinical trial and is willing to participate in the study.
        Exclusion Criteria:
          1. Had previously received CAR T cell therapy;
          2. patients with serious heart, liver, lung, blood system, endocrine system diseases, and
             the risk of participating in the trial is higher than the benefit judged by the
             researcher;
          3. There is an active or uncontrollable infection that requires systemic treatment within
             1 week prior to screening;
          4. have previously received hematopoietic stem cell transplantation or solid organ
             transplantation (except corneal and hair transplantation), or have grade 2 or higher
             acute graft-versus-host disease (GVHD) within 2 weeks prior to screening;
          5. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and
             peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference
             value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood
             hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or
             positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive;
             Or cytomegalovirus (CMV) DNA test positive;
          6. Had received live vaccine within 4 weeks before screening;
          7. pregnancy test positive;
          8. Patients with malignant diseases such as malignant tumors before screening, except for
             adequately treated cervical carcinoma in situ, basal cell or squamous cell skin
             cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ
             after radical surgery;
          9. Patients who had participated in other clinical trials within 3 months prior to
             screening;
         10. Situations in which other investigators consider it inappropriate to participate in
             the study.