autoimmune diseases
Conditions
Interventions
refractory systemic lupus erythematosus (lupus nephritis, immune thrombocytopenia):anti CD19 cell therapy
refractory ANCA-associated vasculitis:anti CD19 cell therapy
Refractory Dermatomyositis:anti-CD19 cell therapy
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Eligible patients or their legal representatives voluntarily sign the informed consent form; 2. Age range: 18-70 years (including 18 and 70 years), male or female; 3. Subjects with refractory systemic lupus erythematosus (lupus nephritis, immune thrombocytopenia): Confirmed diagnosis of systemic lupus erythematosus with lupus nephritis (SLE-LN) or immune thrombocytopenia (SLE-ITP) and receiving standard treatment; (1) Subjects with Refractory Systemic Lupus Erythematosus (Lupus Nephritis): Active and biopsy-confirmed proliferative lupus nephritis grade III or IV or grade V alone according to 2003 ISN/RPS criteria. Active renal disease was defined as a urine protein: creatinine ratio > 1.0 or proteinuria > 3.5 grams/day; (2) Subjects with refractory systemic lupus erythematosus (thrombocytopenia): blood routine examination for at least 2 consecutive times showed platelets less than 50 x 10^9/L; peripheral blood smear microscopy showed no significant abnormality in blood cell morphology; the spleen was generally not enlarged; bone marrow cytomorphology showed megakaryocytes or normal, with maturation disorder; platelet count > 10 x 10^9/L; 4. Subjects with refractory ANCA-associated vasculitis: diagnosis of ANCA glomerulonephritis (GN) or vasculitis based on the definition of AAV in the 2013 American Chapel Hill Consensus Conference (Jennette et al, 2013); Relapsed or refractory AAV requiring treatment with cyclophosphamide or rituximab; Newly diagnosed or relapsed AAV, defined as involvement of at least one major organ (e.g., kidney, lung, heart) requiring induction therapy with cyclophosphamide or rituximab; Positive test for anti-PR3 or anti-MPO (current or historical); 5. Subjects with Refractory Dermatomyositis: Refractory MDA5-positive dermatomyositis is defined as an active disease and meets the following conditions: adequate corticosteroid therapy (greater than two to four weeks of conventional corticosteroid therapy or intolerance to such therapy) and/or use of = 1 conventional immunosuppressive agent (eg, methotrexate, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF, or rituximab) at a reasonable dose and duration (greater than two to four weeks or intolerance to therapy); Treatment with IVIG or cyclophosphamide for two to four weeks; 6. Women of childbearing potential must have a negative blood pregnancy test 7 months prior to trial conditioning therapy; any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 1 year following infusion of CNCT19 CAR-T cells. Childbearing potential, in the judgment of the investigator, is biologically capable of bearing a living baby and being sexually active. Female patients who were not of childbearing potential (ie, met at least 1 of the following criteria): Hysterectomy or oophorectomy, medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence of pathological or physiological causes); 7. Adequate organ function according to the following criteria: (1)Aspartate aminotransferase (AST) <= 3 times of upper limit of normal (ULN); (2)Alanine aminotransferase (ALT) <= 3 times ULN; (3)Total serum bilirubin <= 2 times ULN unless the patient has documented Gilbert's syndrome; patients with Gilbert's syndrome who have bilirubin <= 3.0 times ULN and direct bilirubin <= 5 times
Exclusion criteria
Exclusion criteria: 1. Patients with the severe active central nervous system (CNS) lupus, including seizure disorder, psychosis, cerebrovascular ischemia/hemorrhage, or CNS vasculitis requiring therapeutic intervention within 60 days after baseline; 2. Dialysis patients; 3. Pregnant or lactating women 4. Presence of active infection (e.g., sepsis, bacteremia, fungemia, uncontrolled pulmonary infection, etc.); 5. Known Hepatitis B surface antigen (HBsAg) positive, hepatitis C (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive, syphilis (TP) positive; 6. Major surgery that was assessed as unsuitable for enrollment by the investigator within 4 weeks before screening; 7. Patients with concurrent active malignancy; patients with a history of prior malignancy unless disease free for at least 2 years. 8. Patient's heart meets any of the following: 1) Left ventricular ejection fraction (LVEF) = 450 ms for males and >= 470 ms for females (QTcB = QT/RR1/2); 5) Myocardial infarction, bypass surgery, or stent surgery within 6 months prior to the study; 6) Other cardiac diseases that are not suitable for the study as judged by the investigator; 9. Received a live vaccine within 6 weeks prior to screening. 10. Participation in other interventional clinical studies within 3 months prior to CNCT19 infusion, treatment with an active investigational drug, or intentional participation in another clinical trial or treatment outside of that specified by the protocol throughout the study period 11. Patients with a history of epilepsy or other active central nervous system diseases; 12. Allergic constitution, allergic to macromolecular biological drugs such as antibodies or cytokines; 13. Prior treatment with CAR-T cells; 14. Other conditions that investigators consider inappropriate for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety assessment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Duration of Overall Response;Progression Free Survival ; | — |
Countries
China
Contacts
Public ContactYi Zhang, Shengyun Liu
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed