CAR-T in Subjects With Relapsed/Refractory Autoimmune Disease

Inclusion Criteria36

• age 18-65 years (including threshold) and gender;
• positive expression of CD19 in peripheral blood B cells as determined by flow cytometry;
• the function of vital organs meets the following requirements:
• Bone marrow function needs to meet the following requirements: a. White blood cell count ≥3×109/L; b. Neutrophil count ≥1×109/L (no colony-stimulating factor treatment within 2 weeks prior to the examination); c. Hemoglobin ≥60g/L;
• Liver function: ALT≤3×ULN (except for elevated ALT caused by inflammatory myopathy); AST≤3×ULN (except for AST elevation caused by inflammatory myopathy); TBIL≤1.5×ULN (except for Gilbert's disease).
• TBIL≤1.5×ULN (except Gilbert's syndrome, total bilirubin≤3.0×ULN);
• Renal function: creatinine clearance (CrCl) ≥ 30 ml/minute (Cockcroft/Gault formula, except for disease-induced decline in CrCl);
• Coagulation: international normalized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) ≤ 1.5 x ULN.
• Cardiac function: hemodynamic stability;
• female subjects of childbearing potential and male subjects with a partner of childbearing potential are required to use medically approved contraception or be abstinent from sexual intercourse for at least 6 months during and after study treatment; female subjects of childbearing potential must have had a negative serum HCG test within 7 days prior to study enrollment and must not be breastfeeding;
• Voluntarily participate in this clinical study and sign the informed consent form, good compliance and cooperate with follow-up visits.
• Relapsed refractory systemic lupus erythematosus.
• meets the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE;
• have a Disease Activity Score SLEDAI⁃2000 ≥ 6; and have at least one British Isles Lupus Assessment Group Index (BILAG-2004) Category A (severe manifestations) or two Category B (moderate manifestations) organ scores, or both; or have a Disease Activity Score SLEDAI-2000 ≥ 8;
• Definition of relapse-refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
• Relapsing Refractory/Progressive Diffuse Systemic Sclerosis
• meets the 2013 ACR's classification criteria for systemic sclerosis consistent with a diffuse presentation
• is positive for antibodies related to systemic sclerosis;
• diffuse cutaneous sclerosis manifestations or active interstitial lung disease (HRCT suggestive of ground-glass exudates);
• definition of relapsing-refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
• Definition of Progressive: Rapid cutaneous progression (>25% increase in mRSS); or pulmonary progression (10% decrease in FVC, or >5% decrease in FVC with 15% decrease in DLCO).
• Note: It is sufficient if one of Articles 4 and 5 is fulfilled.
• Relapsed refractory/progressive inflammatory myopathy
• meets the 2017 EULAR/ACR classification criteria for inflammatory myopathies (including DM , PM, ASS, and NM);
• is positive for antibodies to myositis;
• in those with muscle involvement, an MMT-8 score of less than 142 and abnormal findings on at least two of the following five core measurements (PhGA, PtGA, or Extramuscular Disease Activity Score ≥2; Total HAQ Score ≥0.25); Myosin level 1.5 times the upper limit of the normal range); or MMT-8 ≥142 in the presence of active interstitial lung disease (HRCT suggestive of ground-glass exudates);
• Definition of relapse refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
• Definition of progressive: the presence of exacerbation of myositis or rapidly progressive interstitial pneumonia.
• Note: It is sufficient if one of Articles 4 and 5 is fulfilled.
• Relapsed Refractory/Progressive Immune Thrombocytopenia
• meets the 2019 American Society of Hematology (ASH) classification criteria for immune thrombocytopenia;
• have bone marrow morphology characterized by increased or normal megakaryocytes with impaired maturation;
• exclude other secondary thrombocytopenia
• Definition of recurrent refractory: a patient who fails to achieve a satisfactory outcome after first-line standard therapy (e.g., glucocorticoids), including a full dose and course of therapy, i.e., platelet counts that cannot be maintained at a safe level (generally considered to be platelet counts > 30 × 10⁹ /L and without overt bleeding symptoms).
• Definition of progressive: a sustained decline in platelet count over the course of the disease, or a progressive worsening of bleeding symptoms, which may be accompanied by signs such as splenomegaly, and a progressively worse response to conventional therapy.
• Note: It is sufficient if one of Articles 4 and 5 is fulfilled.