UCAR T-cell therapy for patients with systemic lupus erythematosus

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapsed / Refractory Systemic Lupus Erythematosus

This study is testing a new type of CAR T-cell therapy to see if it can help people with tough cases of systemic lupus erythematosus feel better.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang University (other)
• Drugs / interventions: rituximab, Beliumab, methotrexate, cyclophosphamide, CAR T, fludarabine
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06920433 on ClinicalTrials.gov

What this trial studies

This open-label, single-site, dose-escalation study evaluates the safety and efficacy of universal CD19/BCMA CAR T-cells in patients with relapsed or refractory systemic lupus erythematosus. Participants will receive a single infusion of CAR T-cells after undergoing a lymphodepleting therapy regimen with fludarabine and cyclophosphamide. The study aims to enroll up to 18 participants and will conduct an interim analysis 90 days post-infusion to assess treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory systemic lupus erythematosus who have not responded to conventional treatments.

Not a fit: Patients with mild or well-controlled systemic lupus erythematosus may not benefit from this aggressive treatment approach.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option for patients with difficult-to-treat systemic lupus erythematosus.

How similar studies have performed: While CAR T-cell therapies have shown promise in hematological malignancies, their application in systemic lupus erythematosus is novel and largely untested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Meet the 2019 European League against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus; The diagnosis of lupus nephritis was consistent with renal biopsy within 6 months prior to the study, and the histological diagnosis (ISN/RPS2018 LN classification) was active nephritis type III or IV with or without type V. Meet the definition of refractory recurrence: conventional treatment remains ineffective for more than 6 months, or disease activity reappears after remission. Conventional treatment is defined as the use of glucocorticoids, along with one or more of the following immunomodulatory drugs: cyclophosphamide, antimalarial drugs, azathioprine, Mycophenolate Mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics such as rituximab, Beliumab, and Telitacicept.
3. SLEDAI-2000 ≥8；
4. The NIH activity index (AI) of lupus nephritis was \>2, and the chronicity index (CI) was increased; Urinary protein: creatinine ratio (UPCR)\>1.0g/g, or 24-hour urinary protein \>0.5g, with or without active urinary sediment with red blood cell precipitation.
5. Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
6. Functional requirements for major organs are as follows:

   1. The bone marrow function needs to meet: a Neutrophil count ≥ 0.5× 10 \^ 9/L; b. Hemoglobin ≥60g/L: c. Platelets ≥ 20 × 10 \^ 9/L.
   2. Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN# Total bilirubin ≤ 2.0 ×ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
   3. Renal function: creatinine clearance rate (CrCl) ≥ 30 ml/min(Cockcroft/Gault formula, excluding acute CrCl decline caused by the disease itself).
7. ECOG：0-1；
8. Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
9. Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Subjects with a history of severe drug allergies or allergic tendencies.
2. Presence or suspicion of uncontrolled or treatment-required fungal,bacterial, viral, or other infections.
3. Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis).
4. Subjects with insufficient cardiac function
5. Subjects with congenital immunoglobulin deficiencies
6. History of malignancy within five years
7. Subjects with end-stage renal failure
8. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer higher than the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV)
9. Subjects with psychiatric disorders and severe cognitive impairments
10. Subjects who had participated in other clinical trials within 3 months prior to enrollment
11. Subjects who have used immunosuppressive agents or biologics with therapeutic effects on the disease within five half-life before enrollment
12. Pregnant women or women planning to conceive
13. Subjects that the investigator believes have other reasons that make them unsuitable for inclusion in this study.

Where this trial is running

Hangzhou, Zhejiang

• The first affiliated hospital of medical college of zhejiang university — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: He Huang

Conditions: Systemic Lupus Erythematosus, CD19/BCMA CAR T-cells, Universal Allogeneic CAR T-cells