Using CAR-T cells to treat severe systemic lupus erythematosus

A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cell Injection Targeting CD19 Gene in the Treatment of Refractory Systemic Lupus Erythematosus

This study is testing if a new CAR-T cell treatment can help children and adults with severe lupus feel better and reduce their need for long-term medications.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine (Academic / other)
• Drugs / interventions: Beliumab, rituximab, CAR-T, CAR T, methotrexate, cyclophosphamide, prednisone, belimumab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06222853 on ClinicalTrials.gov

What this trial studies

This trial investigates the safety and effectiveness of anti-CD19 CAR-T cells for patients with refractory systemic lupus erythematosus (SLE). SLE is a serious autoimmune disease that can cause significant organ damage, particularly in children. Current treatments are limited and often require lifelong medication without a cure. The study aims to determine if CAR-T cell therapy can effectively target and eliminate autoimmune B cells, potentially allowing patients to discontinue long-term medications and improve their quality of life.

Who should consider this trial

Good fit: Ideal candidates are children and adults aged 5 and older with moderate to severe SLE who have not responded to standard treatments.

Not a fit: Patients with mild SLE or those who have not yet tried multiple standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a curative option for patients suffering from refractory systemic lupus erythematosus.

How similar studies have performed: Previous studies have shown promising results with CAR-T cell therapy in autoimmune diseases, indicating potential for success in this novel application.

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.

Where this trial is running

Hangzhou, Zhejiang

• Children's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jianhua Mao, MD — Children's Hospital, Zhejiang University School of Medicine
• Study coordinator: Jiahua Mao, MD

Conditions Systemic Lupus Erythematosus; CAR-T Cell Therapy; CAR-T