CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

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

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Вьетнам · 1 центр

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

Идентификаторы

NCT: NCT07432334 · ISC25.03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗