CAR T-cell Therapy Targeting CD19 and BCMA(QT-019C) in Patients With Relapse/Refractory Autoimmune Diseases

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• Common Inclusion Criteria:
• Age ≥ 18 years old (inclusive), regardless of gender
• Functional requirements for major organs are as follows（Except for abnormalities related to autoimmune disease activity）: 1) Bone marrow function must meet: A. Neutrophil count ≥ 1×109/L (no colony-stimulating factor treatment within 2 weeks before examination); B. Hemoglobin ≥ 60g/L; 2) Liver function: Alanine aminotransferase (ALT) ≤ 3×ULN (excluding ALT elevation due to inflammatory myopathy), aspartate aminotransferase (AST)≤3×Upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy), TBIL≤2×ULN (or ≤ 3.0×ULN for subjects with Gilbert syndrome); 3) Renal function: creatinine clearance rate (CrCl) ≥ 30mL/minute (calculated by Cockcroft/Gault formula, acute CrCl decrease due to the target disease is excluded; LN is excluded)
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative human chorionic gonadotropin (hCG) test within 7 days before study enrollment and not be lactating
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up; Disease-Specific Inclusion Criteria:; Refractory/Relapsed Systemic Lupus Erythematosus:
• SLE meeting the 2019 American College of Rheumatology (ACR) /European League Against Rheumatism (EULAR) and classification criteria
• Disease activity score SLEDAI-2000 ≥ 8; or with significant organ involvement, such as lupus nephritis (histologically confirmed active nephritis of class III or IV, with or without class V, with an NIH activity index > 2, evidence of increased chronicity index; urine protein-to-creatinine ratio > 1.0 g/g, or 24-hour urinary protein > 1.0 g)
• Definition of refractory or relapsing disease: lack of response after more than 6 months of conventional therapy, or recurrence of disease activity after remission. Conventional therapy is defined as treatment with glucocorticoids in combination with one or more of the following immunomodulatory agents: cyclophosphamide, antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biologics such as rituximab, belimumab, and telitacicept; Refractory/Relapsed/Progressive Systemic Sclerosis:
• Scleroderma fulfilling the 2013 ACR classification criteria
• Positive scleroderma-related antibodies
• Presence of diffuse cutaneous sclerosis or active interstitial lung disease (high-resolution computed tomography (HRCT) showing ground-glass opacities)
• Definition of relapsed/refractory: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids , and any one or more of the following immunomodulatory drugs: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc
• Definition of progressive: Rapid skin progression (mRSS increase > 25%); or progression of lung disease (forced vital capacity (FVC) decrease by 10%, or FVC decrease by more than 5% with diffusing capacity of the lung for carbon monoxide (DLCO) decrease by 15%); Note: Meeting either criterion 4 or 5 is sufficient; Refractory/Relapsed/Progressive Inflammatory Myopathy:
• Inflammatory myopathy fulfilling the 2017 EULAR/ACR classification criteria (including Dermatomyositis (DM), Polymyositis (PM), Anti-Synthetase Syndrome (ASS), and Necrotizing Myopathy (NM))
• Muscle involvement with Manual Muscle Testing-8 (MMT-8) score less than 142 and at least two abnormalities found among the following five core measurements (Physician Global Assessment (PhGA), Patient Global Assessment (PtGA), or extramuscular disease activity score ≥ 2; Health Assessment Questionnaire (HAQ) total score ≥ 0.25; muscle enzyme levels ≥ 1.5×ULN)
• Definition of relapsed/refractory: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids , and any one or more of the following immunomodulatory drugs: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc
• Definition of progressive: Rapid progression of interstitial lung disease within a short period; Note: Meeting either criterion 3 or 4 is sufficient; Refractory/Relapsed ANCA-Associated Vasculitis:
• ANCA-Associated Vasculitis fulfilling 2022 ACR/EULAR criteria, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis
• Positive ANCA-associated antibodies (MPO-ANCA or PR3-ANCA positive)
• The Birmingham Vasculitis Activity Scale (BVAS) ≥ 15 points (a total score of 63 points), indicating active vasculitis
• Definition of refractory/relapsed: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission., or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids and any one or more of the following immunomodulatory drugs: cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc; Refractory/Relapsed Connective Tissue Disease-associated thrombocytopenia:
• Diagnosis of connective tissue disease established according to the latest classification criteria, including but not limited to systemic lupus erythematosus, primary Sjögren's syndrome, antiphospholipid syndrome, and undifferentiated connective tissue disease
• Confirmed diagnosis of connective tissue disease-associated thrombocytopenia, with platelet count <30 × 10\^9/L, or <50 × 10\^9/L accompanied by a bleeding tendency
• Bone marrow morphology consistent with immune thrombocytopenia
• Prior treatment with at least one course of corticosteroid pulse therapy, or high-dose corticosteroids in combination with one or more immunosuppressants (including biologics) for at least 3 months, without achieving partial remission, or inability to maintain efficacy during steroid tapering

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• Subjects who have participated in other clinical trials within the past 3 months prior to enrollment
• Subjects who have received immunosuppressive agents or biologics with therapeutic effects for indications within 5 half-life prior to enrollment
• Subjects with a history of severe drug allergies or allergic tendencies
• Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections
• Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis)
• Subjects with insufficient cardiac function
• History of malignancy within five years
• Subjects with end-stage renal failure(LN is excluded)
• Subjects with psychiatric disorders and severe cognitive impairments
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA >ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing
• Subjects with congenital immunoglobulin deficiencies
• Pregnant women or women planning to conceive
• Subjects whom the investigator believes have other reasons that make them unsuitable for inclusion in this study