Umbilical cord blood CAR-T therapy for refractory systemic lupus erythematosus

Clinical Study on the Safety and Efficacy of Allogeneic, Umbilical Cord Blood Derived CAR T-cell Therapy for Refractory Systemic Lupus Erythematosus

This will test an off-the-shelf umbilical cord blood–derived CAR‑T cell therapy targeting CD19 and BCMA to see if it helps adults with treatment‑resistant SLE.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chengdu Ucello Biotechnology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Yancheng, Jiangsu and 1 other locations)
• Trial ID: NCT07274059 on ClinicalTrials.gov

What this trial studies

This early‑phase interventional protocol gives allogeneic umbilical cord blood–derived CAR‑T cells directed at CD19 and BCMA to adults with refractory SLE, with the aim of identifying an optimal biological dose and characterizing short‑ and longer‑term safety. Participants may receive lymphodepleting chemotherapy (fludarabine plus cyclophosphamide) before a single UCAR‑T infusion, followed by at least 7 days of inpatient monitoring and frequent clinic visits through 24 months. Key outcomes include CAR‑T–related adverse events in the first 3 months and clinical efficacy measures such as DORIS remission, SRI‑4 response, and maintenance of LLDAS. The protocol includes close post‑infusion monitoring and predefined dose escalation to determine safety and biological activity.

Who should consider this trial

Good fit: Adults aged 18–75 with a confirmed 2019 EULAR/ACR diagnosis of SLE who have treatment‑refractory disease (failed ≥2 conventional therapies) and meet the trial's activity and organ‑function criteria are the intended participants.

Not a fit: Patients with mild or well‑controlled SLE, significant organ dysfunction, active uncontrolled infection, or who fail to meet blood and liver function thresholds are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the therapy could produce durable remission and allow some patients to reduce or stop other immunosuppressive medications.

How similar studies have performed: Autologous CD19 CAR‑T has produced encouraging results in small early reports for refractory SLE, but allogeneic umbilical‑cord‑derived CAR‑T targeting both CD19 and BCMA is a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Aged 18 to 75 years (inclusive), regardless of gender.
* Definitive diagnosis of systemic lupus erythematosus (SLE) meeting the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE
* Treatment refractory: failed ≥ 2 conventional SLE treatments for at least 3 months.
* Disease activity assessed by SELENA-SLEDAI score ≥ 6 with at least one British Isles Lupus Assessment Group (BILAG)-2004 Class A (severe manifestation) or two Class B (moderate manifestation) organ scores (or both); OR SELENA-SLEDAI score ≥ 8.
* Adequate function of major organs as follows:

Bone marrow function: a. Neutrophil count ≥ 1 × 10⁹/L (no colony-stimulating factor therapy within 2 weeks prior to testing, excluding neutropenia caused by SLE); b. Hemoglobin ≥ 60 g/L.

Liver function: Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) (excluding ALT elevation caused by SLE); Aspartate aminotransferase (AST) ≤ 3 × ULN (excluding AST elevation caused by SLE); Total bilirubin (TBIL) ≤ 1.5 × ULN (excluding TBIL elevation caused by SLE).

Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/minute (calculated by Cockcroft/Gault formula, excluding CrCl reduction caused by SLE).

Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN; Prothrombin time (PT) ≤ 1.5 × ULN.

Cardiac function: Hemodynamically stable.

* Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must use medically approved contraceptive methods or abstain from sexual intercourse during the study treatment period and for at least 6 months after the end of study treatment. Female subjects of childbearing potential must have a negative serum human chorionic gonadotropin (HCG) test within 7 days prior to study enrollment and must not be breastfeeding.
* Voluntarily agrees to participate in the clinical study, signs the informed consent form (ICF), and demonstrates good compliance with study procedures and follow-up.

Exclusion Criteria:

* History of severe drug allergies or atopic diathesis.
* Presence or suspicion of uncontrolled or treatment-requiring fungal, bacterial, viral, or other infections.
* Cardiac function insufficient to tolerate the study treatment.
* Congenital immunoglobulin deficiency.
* History of malignant tumors within the past 5 years.
* End-stage renal failure.
* Positive for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the lower limit of detection; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody; positive syphilis test.
* History of mental illness or severe cognitive impairment.
* Use of disease-modifying immunosuppressive agents within 5 half-lives or biological agents within 4 weeks prior to enrollment.
* Pregnant females or females planning to become pregnant.
* Other conditions deemed by the investigator to preclude study participation.

Where this trial is running

Yancheng, Jiangsu and 1 other locations

• Yancheng Third People's Hospital — Yancheng, Jiangsu, China (Recruiting)
• The General Hospital of Western Theater Command — Chengdu, Sichuan, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Tao Wang, M.D. — The General Hospital of Western Theater Command
• Study coordinator: Tao Wang, M.D.

Conditions SLE - Systemic Lupus Erythematosus; allogeneic; CAR-T; umbilical cord blood; SLE