UCAR T-cell Therapy Targeting CD19/BCMA in Patients With r/r Systemic Lupus Erythematosus

NCT06920433 | Recruiting Early Phase 1

• 1 other identifier: QH-ZY-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single-site, dose-escalation study in up to 18 participants with relapsed or refractory Systemic lupus erythematosus. This study aims to evaluate the safety and efficacy of the treatment with universal CD19/BCMA CAR T-cells.

Conditions

Systemic Lupus Erythematosus

Keywords

CD19/BCMA CAR T-cells; Universal Allogeneic CAR T-cells

Outcome Measures

Primary Outcomes (3)

• The number and severity of dose-limiting toxicity (DLT) events

  DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, and the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.

  Within 28 Days After UCAR T-cell Infusion

• The total number, incidence, and severity of AEs

  Up to 90 days After UCAR T-cell Infusion

• Clinical response

  SLE：SLE Response Index 4 (SRI-4) LN：Primary effcacy renal response（PERR）

  Up to 24 Months After UCAR T-cell Infusion

Study Arms (1)

UCAR T-cell group

EXPERIMENTAL

Universal allogeneic CD19/BCMA CAR T-cells

Biological: UCAR T-cell group

Interventions

UCAR T-cell group BIOLOGICAL

A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells

UCAR T-cell group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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.
• SLEDAI-2000 ≥8；
• 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.
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Functional requirements for major organs are as follows:
• 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.
• Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN# Total bilirubin ≤ 2.0 ×ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
• Renal function: creatinine clearance rate (CrCl) ≥ 30 ml/min(Cockcroft/Gault formula, excluding acute CrCl decline caused by the disease itself).
• ECOG：0-1；
• 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.
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Subjects with a history of severe drug allergies or allergic tendencies.
• Presence or suspicion of uncontrolled or treatment-required fungal,bacterial, viral, or other infections.
• 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).
• Subjects with insufficient cardiac function
• Subjects with congenital immunoglobulin deficiencies
• History of malignancy within five years
• Subjects with end-stage renal failure
• 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)
• Subjects with psychiatric disorders and severe cognitive impairments
• Subjects who had participated in other clinical trials within 3 months prior to enrollment
• Subjects who have used immunosuppressive agents or biologics with therapeutic effects on the disease within five half-life before enrollment
• Pregnant women or women planning to conceive

Sponsors & Collaborators

• Zhejiang University: lead
• Shanghai Xiniao Biotech Co., Ltd.: collaborator

Study Sites (1)

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

He Huang

CONTACT

86-13605714822; hehuangyu@126.com

Yongxian Hu

CONTACT

86-15957162012; Huyongxian2000@aliyun.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: April 8, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 1, 2025

Record last verified: 2025-04

Locations

CN (1)