Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cells in Refractory Systemic Lupus Erythematosus

Launched by THE CHILDREN'S HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE · Jan 15, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment using a special type of immune cell therapy called anti-CD19 CAR-T cells for patients with systemic lupus erythematosus (SLE) who have not responded well to standard treatments. The goal is to see if this therapy is safe and effective for those who still experience moderate to severe symptoms despite trying multiple other medications, including high doses of steroids and other immunosuppressants. The trial is currently looking for participants aged 5 and older who meet specific health criteria and have been diagnosed with SLE.

Eligible participants will undergo a procedure to collect their blood cells, which will then be modified in the lab to create the CAR-T cells before being infused back into their bodies. Throughout the trial, participants can expect close monitoring by healthcare professionals to assess their health and any potential side effects from the treatment. It's important for interested individuals or their guardians to understand the purpose of the trial and to give informed consent before joining.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Age:≥5 years old;
• • 2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab); or Intolerant to standard treatments;
• • 3. SLEDAI 2K score≥8 points;
• 4. The functions of important organs are basically normal:
• • Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2； Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; Lung function: No serious lung lesions, SpO2≥92%;
• • 5. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• • 6. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• • 7. Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.
• Exclusion Criteria:
• • 1. Received CAR T cell therapy previously;
• • 2. Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• • 3. Severe acute nephritis: Patients who have accepted or was undergoing renal replacement therapy within 3 months prior to transfusion; Or in the investgator's opinion, patients who is likely to have significant kidney disease within 3 moths of the study which need high dose glucocorticoid (prednisone dose≥1mg/kg/day or equivalent amount of other steriod), cyclophosphamide, or MMF treatment;
• • 4. Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
• • 5. Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
• • 6. Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
• • 7. History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
• • 8. 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;
• • 9. Received live vaccine within 4 weeks before screening;
• • 10. Tested positive in Blood pregnancy test；
• • 11. Previous or concurrent malignancy；
• • 12. Patients who participated in other clinical study within 3 months prior to enrollment;
• • 13. Any other conditions that the investigators deem it unsuitable for the study.