CAR T cell therapy for children with lupus nephritis

An Exploratory Clinical Study of the Safety and Efficacy of CAR-T in Children With Refractory/Recurrent Lupus Nephritis Disease

This study is testing a new CAR T cell therapy to see if it can help children with lupus nephritis who haven't responded to other treatments.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 6 Years to 18 Years
• Sex: All
• Sponsor: Guangzhou Women and Children's Medical Center (other)
• Drugs / interventions: CAR-T, cyclophosphamide, CAR T
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06904729 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and potential efficacy of chimeric antigen receptor (CAR) T cell therapy in children aged 6 to 18 with refractory or recurrent lupus nephritis. It is a prospective, open-label, single-arm study that involves administering either low-dose or high-dose CAR T cells to participants. The study aims to assess the persistence and phenotype of CAR T cells in the body, as well as the inflammatory factors related to the treatment. The ultimate goal is to explore new therapeutic methods that can reduce the side effects of traditional treatments and improve long-term survival and quality of life for patients.

Who should consider this trial

Good fit: Ideal candidates are children aged 6-18 diagnosed with systemic lupus erythematosus and active Class III or IV lupus nephritis who have not responded to multiple immunosuppressive treatments.

Not a fit: Patients who do not have active lupus nephritis or those who have not undergone prior immunosuppressive therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option that significantly improves outcomes for children suffering from refractory lupus nephritis.

How similar studies have performed: While CAR T cell therapy has shown promise in other conditions, this specific application for lupus nephritis in children is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age 6-18 years old (including critical value);
2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;
3. According to the 2018 ISN/RPS LN standards diagnosed with active Class III or IV LN, with or without a membranous component and the biopsy must be performed within 6 months prior to screening;
4. SLEDAI-2000 score ≥8 points;
5. Meeting the diagnosis of refractory lupus nephritis,

   1. defined as treatment with two or more immunosuppressants (including glucocorticoids, cyclophosphamide, tacrolimus, mycophenolic acid analogues, leflunomide, and cyclosporine) for more than 6 months without inducing remission or relapse after remission,
   2. accompanied by proteinuria without remission;
6. Positive expression of CD19 in peripheral blood B cells determined by flow cytometry;
7. Participants had good venous access, no contraindications for cell collection;
8. Participants and their guardians sign the informed consent, understand the study procedures and participate in the clinical study voluntarily;
9. The functions of important organs are basically normal:

   1. Hematopoietic function (blood routine should meet):

      * Lymphocyte count ≥1×109/L,
      * White blood cell count ≥3×109/L,
      * Neutrophil count ≥1×109/L (no colony-stimulating factor treatment within 2 weeks prior to examination),
      * Hemoglobin ≥60g/L;
   2. Liver function:

      * ALT≤3×ULN (except elevated ALT caused by inflammatory myopathy),
      * AST≤3×ULN (except for elevated AST caused by inflammatory myopathy),
      * TBIL≤1.5×ULN (except Gilbert syndrome, total bilirubin ≤3.0×ULN);
   3. Renal function: eGFR ≥30 ml/(min.1.73m2) (Schwartz formula, except abnormal renal function by SLE);
   4. Coagulation function:

      * International standardized ratio (INR) ≤1.5×ULN,
      * prothrombin time (PT) ≤1.5×ULN;
   5. Heart function: hemodynamic stability;
10. Anti-nuclear antibody (ANA) ≥1:80;
11. Eastern Cancer Cooperation Group (ECOG) physical status score 0 to 2.

Exclusion Criteria:

1. Received kidney transplant previously;
2. Serious drug allergy history or allergy;
3. Presence or suspicion of fungal, bacterial, viral or other infections that cannot be controlled or require treatment;
4. Complicated with severe organ dysfunction of heart, liver, lung or coagulation dysfunction;
5. Complicated with congenital immunoglobulin deficiency;
6. Participants with infectious diseases:

   1. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBc Ab) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range;
   2. Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range;
   3. Human immunodeficiency virus (HIV) antibody positive;
   4. Syphilis positive;
7. Diagnosed with malignant tumors in the last five years.
8. Suffer from severe central nervous system disease, mental illness and severe cognitive dysfunction;
9. Participated in other clinical trials within 3 months before enrollment;
10. Received CAR-T therapy previously;
11. Other situations that the researcher considers unsuitable for inclusion.

Where this trial is running

Guangzhou, Guangdong

• Guangzhou Women and Children Medical Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Xia Gao, M.D.

Conditions: Lupus Nephritis