CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus

NCT07432334 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ISC25.03
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase I clinical trial is to evaluate the safety and tolerability of autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy in adults with refractory systemic lupus erythematosus who have demonstrated inadequate response to standard-of-care immunosuppressive treatments. The primary questions this study aims to address are: What is the incidence, nature, and severity of treatment-emergent adverse events following CD19 CAR-T cell infusion? Is administration of CD19 CAR-T cell therapy feasible and tolerable in patients with refractory systemic lupus erythematosus? This study is conducted as a single-arm trial without a comparison group. Participants will: Undergo leukapheresis for collection of autologous peripheral blood mononuclear cells Receive a protocol-defined lymphodepleting chemotherapy regimen prior to CAR-T cell infusion Receive a single intravenous infusion of approximately 1.0 × 10⁶ CD19 CAR-T cells per kilogram of body weight Undergo scheduled clinical evaluations, laboratory testing, and longitudinal follow-up to assess safety, tolerability, and clinical parameters

Conditions

Refractory Systemic Lupus Erythematosus

Keywords

CD19 CAR-T; Autoimmune Disease

Outcome Measures

Primary Outcomes (1)

• Assessment of Frequency and Severity of Adverse Events and Serious Adverse Events

  Incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded according to ASTCT criteria.

  From CAR-T cell infusion through Day 360

Secondary Outcomes (6)

• Proportion of Participants Achieving Remission According to DORIS Criteria

  Day 90 and Day 360

• Proportion of Participants Achieving Lupus Low Disease Activity State (LLDAS)

  Day 90 and Day 360

• Proportion of Participants Experiencing Disease Relapse

  From Day 90 through Day 360

• Manufacturing Success Rate of Autologous CD19 CAR-T Cells

  From leukapheresis through product release, up to 12 days

• Peripheral CD19+ B-Cell Depletion and Reconstitution

  Baseline, Day 7, Day 14, Day 28, Day 90, Day 180, and Day 360

Study Arms (1)

CD19 CAR-T Cell Therapy

EXPERIMENTAL

Participants will receive autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy following leukapheresis and protocol-defined lymphodepleting chemotherapy. A single intravenous infusion of CD19 CAR-T cells will be administered, with subsequent safety monitoring and follow-up according to the study protocol.

Biological: Autologous CD19-Targeted CAR-T Cells

Interventions

Autologous CD19-Targeted CAR-T Cells BIOLOGICAL

Autologous chimeric antigen receptor T cells targeting CD19, manufactured from participants' peripheral blood T cells collected by leukapheresis. Cells are genetically modified ex vivo to express a CD19-specific CAR, expanded, and administered as a single intravenous infusion following protocol-defined lymphodepleting chemotherapy. Participants undergo post-infusion monitoring for safety and immunological effects according to the study protocol.

CD19 CAR-T Cell Therapy

Eligibility Criteria

• Age: 16 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 16 to 55 years, male or female
• Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria with a total score ≥ 10
• SLEDAI-2K score ≥ 8 at screening (with at least 4 points derived from laboratory parameters; excluding points attributable to central nervous system involvement)
• Positive antinuclear antibody (ANA ≥ 1:80) OR positive anti-dsDNA OR positive anti-Sm antibody at screening or documented in medical history
• Refractory systemic lupus erythematosus or refractory lupus nephritis defined as one of the following:
• Refractory SLE:
• \- Failure to achieve adequate response, partial response, or stable disease control after ≥ 6 months of standard-of-care therapy (documented compliance). Standard therapy includes corticosteroids plus hydroxychloroquine and at least two of the following: calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, or B-cell-targeted therapy (e.g., rituximab, belimumab).
• Refractory Lupus Nephritis:
• Persistent active lupus nephritis after two induction regimens, including intravenous cyclophosphamide and mycophenolate mofetil administered for ≥ 6 months (with or without calcineurin inhibitors, rituximab, or belimumab), AND:
• Histopathologic confirmation of Class III or Class IV lupus nephritis, with or without Class V (ISN/RPS 2003 classification); isolated Class V is excluded
• Proteinuria \> 1 g/24 hours OR urine protein-to-creatinine ratio \> 1 mg/mg
• Adequate organ function:
• ALT ≤ 5 × upper limit of normal; total bilirubin ≤ 34 μmol/L (≤ 2.0 mg/dL)
• Pulmonary function: FVC ≥ 60% predicted OR FEV1 ≥ 60% predicted
• Cardiac function: LVEF ≥ 50%, no uncontrolled arrhythmia, no intracardiac thrombus, no heart failure

You may not qualify if:

• History of significant neurologic disorders (e.g., traumatic brain injury, seizure disorder, hemorrhagic conditions, impaired consciousness)
• Significant cardiovascular disease within 3 months prior to screening (e.g., uncontrolled hypertension, NYHA Class III-IV heart failure, severe arrhythmia, unstable angina, myocardial infarction)
• Prior kidney transplantation
• Severe asthma requiring long-term treatment or respiratory failure
• Severe hemolytic anemia requiring transfusion at intervals ≤ 7 days
• Active viral infections (e.g., hepatitis B or C, HIV, tuberculosis, malaria, syphilis, CMV, EBV) or other life-threatening infectious diseases
• Active bacterial infection confirmed by clinical evaluation, imaging, or laboratory testing
• Use of the following prior to leukapheresis:
• Anti-CD20 therapy, cyclophosphamide, live or attenuated vaccines within 1 month
• Systemic corticosteroids \> 10 mg/day (prednisone equivalent), T-cell-targeted therapy (e.g., mycophenolate mofetil, calcineurin inhibitors), immunosuppressive agents, or antimalarial agents within 7 days
• Prior anti-CD19 therapy
• Prior T-cell-based cellular therapy or gene therapy, including CAR-T therapy
• Current or prior malignancy
• Known hypersensitivity to study-related agents
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Vinmec Research Institute of Stem Cell and Gene Technology: lead

Study Sites (1)

Vinmec Research Institute of Stem Cell and Gene Technology

Hanoi, 10000, Vietnam

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Liem T Nguyen, PhD

  Vinmec Research Institute of Stem Cell and Gene Technology, VinUniversity

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liem T Nguyen, PhD

CONTACT

+84 986 565 015; liem.nt@vinuni.edu.vn

Van T Hoang, PhD

CONTACT

+84 936 449 481; van.ht@vinuni.edu.vn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 25, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

VN (1)