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

Phase 1

Active, not recruiting

• Conditions: Systemic Lupus Erythematosus; CAR-T Cell Therapy
• Interventions: Biological: anti-CD19-CAR-T cells

• Registration Number: NCT06222853
• Lead Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Brief Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-CD19 CAR-T cells in the treatment of childhood-onset refractory systemic lupus erythematosus.

Detailed Description

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death. Children with SLE are particularly at risk of organ damage, especially to the kidneys, and tend to have a more severe and protracted course of the disease compared to adults.

Currently, the primary treatment for SLE relies on glucocorticoids and immunosuppressants to alleviate symptoms. However, due to the absence of a curative treatment, patients often require lifelong medication. In recent years, biological agents such as belimumab and rituximab have been introduced for the treatment of SLE, but these agents cannot completely eliminate autoimmune B cells in the bone marrow, leading to unsatisfactory overall outcomes. Furthermore, stopping the drugs can lead to relapse, and there is still no cure for SLE, leaving patients facing the challenges of lifelong medication and an incurable disease.

Since 2019, CAR-T cell therapy has been successfully applied to autoimmune diseases. Clinical studies have demonstrated that targeted CD19 CAR-T cells hold significant therapeutic potential for SLE. These cells effectively slow down the pathological progression of SLE and can also effectively treat severe cases. Furthermore, targeted CD19 CAR-T cells are also expected to restore the immune system in SLE patients, potentially allowing them to discontinue lifelong medication and avoid serious long-term side effects of drugs like hormones and immunosuppressants. The purpose of this study is to assess the safety and efficacy of the anti-CD19 CAR-T cells in the treatment of childhood-onset refractory SLE.

Study Timeline

• Study First Submitted: 2024-01-04
• Study First Submitted QC: 2024-01-15
• Study First Posted: 2024-01-25
• Study Start: 2024-02-10
• Primary Completion: 2025-04-04
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-26
• Last Update Posted: 2025-09-03
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

1. Age:5-18 years old(including threshold);

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T treatment group	anti-CD19-CAR-T cells	This trial was designed as an open, single-arm, multicenter, dose-increasing trial. three dose groups (0.3×10\^5/kg, 1×10\^5/kg, 3×105/kg) are set up, starting from the low dose group to explore the safe and effective dose.

Primary Outcome Measures

Name	Time	Method
The safety of CAR-T cell in refractory Systemic Lupus Erythematosus	3 Months	Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.
The efficacy of CAR-T cells in refractory Systemic Lupus Erythematosus	3 months	The 3M SRI-4 response rate is the percentage of subjects who simultaneously achieve: a ≥4-point reduction in SLEDAI-2K, no ≥0.3-point increase in the 3-point PGA score, and no new BILAG grade A or ≥2 grade B organ system manifestations at 3 months post-infusion.The LLDAS response rate is the proportion of subjects meeting these criteria at 3 months post-infusion: ①SLEDAI-2K ≤4, no major organ activity (kidney, CNS, heart, lungs), no vasculitis, and no fever; ② no new lupus activity; ③ PGA score ≤1; ④ serological activity allowed; ⑤ ≤7.5mg prednisolone daily and stable immunosuppressive or biologic doses tolerated. The DORIS response rate is the proportion of subjects meeting these criteria at 3 months post-infusion: a clinical SLEDAI-2K score of 0, a PGA score \<0.5, allowed serological activity, and permitted use of low-dose glucocorticoids (≤5mg prednisolone daily) and well-tolerated standard doses of antimalarials, immunosuppressants, or biologics.

Secondary Outcome Measures

Name	Time	Method
Cellular kinetics	6 Months	CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood.
Serological biomarkers detection	24 Months	The changes in serological biomarkers, including anti-dsDNA antibodies, 24h urinary protein levels, serum complement C3 and C4 levels after infusion.
Duration of disease response (DOR)	24 Months	The time between the first investigator assessment of remission and the first investigator assessment of progression or death from any cause.

Trial Locations

Locations (1)

Children's Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China