CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus

Official title

Evaluation of the Safety and Efficacy of CD19 CAR T-Cell Therapy for the Treatment of Refractory Systemic Lupus Erythematosus: A Phase I Clinical Trial

Overview

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

Detailed description

This is a Phase I, single-center, open-label clinical trial evaluating the safety of autologous CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy in patients with refractory systemic lupus erythematosus (SLE).

Systemic lupus erythematosus is a chronic autoimmune disease characterized by immune dysregulation and pathogenic autoantibody production, with B lymphocytes playing a central role in disease pathophysiology. Targeting CD19-expressing B cells represents a potential therapeutic strategy for patients with disease refractory to standard immunosuppressive therapies.

Autologous CD19 CAR-T cells will be generated from peripheral blood T cells collected by leukapheresis. Cells will be genetically modified ex vivo to express a CD19-specific chimeric antigen receptor, expanded, and released for clinical administration following protocol-defined quality control testing and regulatory requirements.

Participants will receive a lymphodepleting chemotherapy regimen prior to a single intravenous infusion of CD19 CAR-T cells. Treatment administration and post-infusion monitoring will be conducted according to the protocol-specified safety and observation plan.

Following infusion, participants will be monitored for treatment-emergent adverse events, including CAR-T-associated toxicities such as cytokine release syndrome, immune effector cell-associated neurotoxicity, cytopenias, and infections. Safety evaluations will include serial clinical assessments and laboratory monitoring.

Exploratory assessments will evaluate immunological parameters, including B-cell depletion and reconstitution, autoantibody profiles, and selected biomarkers of disease activity. Participants will undergo longitudinal follow-up to assess early and delayed adverse events and the persistence of immunological effects, in accordance with regulatory guidance for gene-modified cell therapies.

Interventions

• Biological Autologous CD19-Targeted CAR-T Cells
  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.

Primary outcome measures

• Assessment of Frequency and Severity of Adverse Events and Serious Adverse Events [Time frame: From CAR-T cell infusion through Day 360]

Secondary outcome measures (6)

• Proportion of Participants Achieving Remission According to DORIS Criteria [Time frame: Day 90 and Day 360]
• Proportion of Participants Achieving Lupus Low Disease Activity State (LLDAS) [Time frame: Day 90 and Day 360]
• Proportion of Participants Experiencing Disease Relapse [Time frame: From Day 90 through Day 360]
• Manufacturing Success Rate of Autologous CD19 CAR-T Cells [Time frame: From leukapheresis through product release, up to 12 days]
• Peripheral CD19+ B-Cell Depletion and Reconstitution [Time frame: Baseline, Day 7, Day 14, Day 28, Day 90, Day 180, and Day 360]
• CAR-T Cell Expansion and Persistence [Time frame: Baseline, Day 7, Day 14, Day 28, Day 90, Day 180, and Day 360]

Eligibility criteria

Inclusion criteria

• 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
• Adequate hematologic parameters:

• Absolute neutrophil count ≥ 0.8 × 10⁹/L (without growth factor support)
• Absolute lymphocyte count ≥ 0.3 × 10⁹/L
• Platelet count ≥ 50 × 10⁹/L
• Hemoglobin ≥ 80 g/L (≥ 8.0 g/dL)
• Ability to provide written informed consent
• Agreement to use effective contraception during the study period (for participants of reproductive potential)

Exclusion criteria

• 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
• Active antiphospholipid syndrome (stable antiphospholipid antibody positivity without active APS is permitted)
• Participation in another clinical trial at the time of screening
• Any condition that, in the investigator's judgment, would interfere with protocol compliance or study participation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Vietnam · 1 center

• Vinmec Research Institute of Stem Cell and Gene Technology — Hanoi

Identifiers

NCT: NCT07432334 · ISC25.03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗