Refractory Systemic Lupus Erythematosus
Conditions
Keywords
CD19 CAR-T, Autoimmune Disease
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
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
BIOLOGICALAutologous 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.
Sponsors
Vinmec Research Institute of Stem Cell and Gene Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Frequency and Severity of Adverse Events and Serious Adverse Events | From CAR-T cell infusion through Day 360 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Remission According to DORIS Criteria | Day 90 and Day 360 | Proportion of participants achieving complete or partial remission according to the Definitions of Remission in SLE (DORIS) criteria. |
| Proportion of Participants Achieving Lupus Low Disease Activity State (LLDAS) | Day 90 and Day 360 | Proportion of participants meeting Lupus Low Disease Activity State (LLDAS) criteria. |
| Proportion of Participants Experiencing Disease Relapse | From Day 90 through Day 360 | Proportion of participants with disease relapse after achieving clinical response. |
| Manufacturing Success Rate of Autologous CD19 CAR-T Cells | From leukapheresis through product release, up to 12 days | Proportion of enrolled participants for whom autologous CD19 CAR-T cells are successfully manufactured and released for administration |
| Peripheral CD19+ B-Cell Depletion and Reconstitution | Baseline, Day 7, Day 14, Day 28, Day 90, Day 180, and Day 360 | Quantitative assessment of peripheral blood CD19+ B-cell counts at specified time points following CAR-T cell infusion. |
| CAR-T Cell Expansion and Persistence | Baseline, Day 7, Day 14, Day 28, Day 90, Day 180, and Day 360 | Quantitative assessment of circulating CAR-T cell levels in peripheral blood at specified time points following infusion. |
Countries
Vietnam
Contacts
CONTACTLiem T Nguyen, PhD
CONTACTVan T Hoang, PhD
PRINCIPAL_INVESTIGATORLiem T Nguyen, PhD
Vinmec Research Institute of Stem Cell and Gene Technology, VinUniversity
Outcome results
None listed