Refractory autoimmune disease
Conditions
Interventions
QH103 cell injection:QH103 cell injection (CD19 CAR-?dT cells)
Sponsors
Bejing GoBroad Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Adults aged 18-65 years old (including 18 years old and 65 years old) at the time of signing the ICF, regardless of gender; 2. Positive expression of CD19 in peripheral blood B cells as determined by flow cytometry; 3. The function of vital organs meets the following requirements: 1) Bone marrow function needs to meet: a. white blood cell count=3×109/L; b. Neutrophil count = 1×109/L (no colony-stimulating factor treatment within 2 weeks before examination); c. Hemoglobin =60g/L; d. Absolute number of lymphocytes=0.3×109/L; Platelet count = 50 × 109/L. 2) Liver function needs to meet: ALT=3×ULN; AST=3×ULN; TBIL=1.5×ULN; Total bilirubin = 3.0×ULN; 3) Renal function needs to be met: Renal function needs to be met: creatinine clearance (CrCl) =30 ml/min (Cockcroft/Gault formula, except for acute CrCl decline caused by the disease itself); 4) Coagulation function should meet the following requirements: international normalized ratio (INR) =1.5×ULN, prothrombin time (PT) =1.5×ULN; 5) Cardiac function: left ventricular ejection fraction =50%. 4. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential who need to use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment period; Female subjects of childbearing age have a negative serum HCG test within 7 days before study enrollment and are not lactating; 5. Voluntarily participate in this clinical study, and sign the informed consent form, with good compliance and follow-up. Disease-specific inclusion criteria: Relapsed and refractory systemic lupus erythematosus 1. Meet the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria [16]; 2. Disease activity score: SLEDAI-2000 [17] =6; 3. and at least one British Island Lupus Rating Group Index (BILAG-2004) class A (severe performance) or two B class B (moderate performance) organ scores, or both [18]; or disease activity score SLEDAI?2000=8; 4. Definition of relapse and refractory: relapse and refractory treatment after more than 6 months of conventional treatment or recurrence of disease activity after remission. Definition of conventional treatment: use of glucocorticoids and cyclophosphamide, and any one or more of the following: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, tataercept, etc. Relapsed refractory/progressive diffuse systemic sclerosis 1. Meet the 2013 ACR classification criteria for systemic sclerosis [19]; 2. Positive for systemic sclerosis-related antibodies; 3. Diffuse sclerotic manifestations or active interstitial lung disease (ground-glass exudation on HRCT) [20]. 4. Definition of relapse and refractory: relapse and refractory treatment after more than 6 months of conventional treatment or recurrence of disease activity after remission. Definition of conventional treatment: use of glucocorticoids and cyclophosphamide, and any one or more of the following: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, tataercept, etc. 5. Definition of progressiveness: rapid skin progression (increase in mRSS >25%); or pulmonary disease progression (10% reduction in FVC, or >5% reduction in FVC with 15% reduction
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Those with a history of severe drug allergies or allergies; 2. Presence or suspicion of uncontrollable fungal, bacterial, viral, or other infections requiring treatment; 3. Patients with central nervous system diseases caused by or not caused by ADs (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis); 4. Cardiac function intolerance; 5. Subjects with congenital immunoglobulin deficiency; 6. History of malignant tumor within the past five years; 7. Subjects with end-stage renal failure; 8. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and have peripheral blood HBV DNA titers higher than the upper limit of detection; Those who are positive for hepatitis C virus (HCV) antibody and HCV RNA in peripheral blood; Those who are positive for human immunodeficiency virus (HIV) antibodies; Those who test positive for syphilis; 9. Have psychiatric illness and severe cognitive dysfunction; 10. Those who have participated in other clinical trials within 3 months before enrollment; 11. The drug is still in the washout stage (evaluated separately for different treatments) or has a great impact on the safety and effective rate of subsequent QH103 cell injection treatment; 12. In the opinion of the investigator, there are other subjects who cannot be included in this study for other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity (DLT);SRI-4; | — |
Countries
China
Contacts
Public ContactHuKai
Bejing GoBroad Hospital
Outcome results
None listed