BCMA/CD70 CAR-T therapy for treating severe lupus in children

Study of BCMA/CD70 Targeted Chimeric Antigen Receptor T (CAR- T) Therapy for Refractory Childhood-oneset Systemic Lupus Erythematosus

This study is testing a new CAR-T cell therapy to see if it can help children and young adults with severe lupus who haven't responded well to other treatments.

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, methotrexate, cyclophosphamide, prednisone, belimumab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06934447 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of anti-BCMA/CD70 CAR-T cells in children and young adults with refractory systemic lupus erythematosus (SLE). The study targets patients who have not responded adequately to conventional treatments, including glucocorticoids and immunosuppressants. By utilizing CAR-T cell therapy, which modifies a patient's T cells to better attack B cells involved in the autoimmune response, the trial aims to provide a more effective treatment option for this challenging condition. The study will assess various health parameters to ensure participant safety and monitor treatment outcomes.

Who should consider this trial

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

Not a fit: Patients who have previously undergone CAR-T therapy or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a curative approach for patients suffering from refractory systemic lupus erythematosus.

How similar studies have performed: While CAR-T therapy has shown promise in treating other conditions, this specific application for refractory SLE is novel and has not been extensively tested.

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 as follows: 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. No prior CAR-T therapy; or recurrence or poor response after previous treatment with autologous or allogeneic CAR-T targeting CD19 (as assessed by the investigator).
6. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
7. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
8. 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. Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
2. 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;
3. 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；
4. Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
5. Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
6. History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
7. 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;
8. Received live vaccine within 4 weeks before screening;
9. Tested positive in Blood pregnancy test；
10. Previous or concurrent malignancy；
11. Patients who participated in other clinical study within 1 months prior to enrollment; Any other conditions that the investigators deem it unsuitable for the study.

Where this trial is running

Hangzhou, Zhejiang

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

Study contacts

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

Conditions CAR T Cell Therapy; Systemic Lupus Erythematosus; BCMA; systemic lupus erythematosus; Chimeric antigen receptor T-cell