Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system mistakenly attacks the body's own tissues and organs. The disease can affect the skin, joints, kidneys, blood cells, brain, and other organs, leading to significant health problems and reduced quality of life. Although several treatments are available, some patients continue to have active disease despite receiving standard therapies.
Recent research has shown that B cells, a type of immune cell, play a central role in the development and persistence of SLE. CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is an innovative treatment that uses a patient's own immune cells, genetically modified to recognize and eliminate B cells. This approach has already shown remarkable success in certain blood cancers and has recently produced encouraging results in patients with severe autoimmune diseases, including SLE.
The CLEVER-SLE study is a Phase I/II clinical trial designed to evaluate the safety and potential effectiveness of CD19-directed CAR-T cell therapy produced at Ribeirao Preto Blood Bank in patients with SLE who have not responded adequately to conventional treatments. Participants will undergo the collection of their own immune cells, which will be modified in a specialized laboratory to produce CAR-T cells. After receiving preparatory chemotherapy, participants will receive a single intravenous infusion of these CAR-T cells.
The main goal of this study is to evaluate the safety of this treatment. Researchers will also assess its effects on disease activity, symptoms, organ involvement, medication requirements, immune system markers, and the duration of clinical responses. The study aims to determine whether CD19-directed CAR-T cell therapy can provide a new treatment option for patients with refractory SLE and contribute to the development of CAR-T therapies for autoimmune diseases.
Adults aged 18 to 50 years, inclusive.
Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 ACR/EULAR classification criteria.
Active disease at screening, defined as SLEDAI-2K ≥4 and Physician Global Assessment (PGA) ≥0.5.
Inadequate response, intolerance, or contraindication to corticosteroids and at least two of the following therapies: azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, belimumab, rituximab, or tacrolimus.
Severe pulmonary hypertension (estimated pulmonary artery systolic pressure >50 mmHg).
Requirement for systemic anticoagulation at screening.
Clinically significant cardiovascular disease, including NYHA Class III/IV heart failure, myocardial infarction, unstable arrhythmias, or unstable angina within the previous 6 months.
Active neurological disease (stroke, epilepsy, or neurodegenerative disorders) within the previous 12 months.
Single group
Autologous CD19-Directed CAR-T Cells Manufactured at Ribeirão Preto Blood Center
Biological/VaccineAutologous CD19-directed chimeric antigen receptor T (CAR-T) cells developed and manufactured at the Ribeirão Preto Blood Center (Hemocentro de Ribeirão Preto, Brazil). T lymphocytes collected by leukapheresis are genetically modified ex vivo using a lentiviral vector to express a CD19-specific chimeric antigen receptor and subsequently expanded under Good Manufacturing Practice (GMP) conditions. Following standard lymphodepleting chemotherapy, participants receive a single intravenous infusion of the autologous CAR-T cell product. The therapy is intended to achieve deep and sustained depletion of CD19-positive B cells implicated in the pathogenesis of systemic lupus erythematosus.
Incidence and Severity of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Incidence and maximum grade of CRS and ICANS following infusion of autologous CD19-directed CAR-T cells, assessed according to ASTCT consensus criteria.
Incidence of Grade ≥3 Cytopenias
Incidence of grade ≥3 anemia, neutropenia, lymphopenia, and thrombocytopenia according to CTCAE v6.0.
Time to Hematologic Recovery
Time to resolution of cytopenias to grade \<1.
Incidence and Severity of Infections
Cumulative incidence and severity of infections
Incidence of Serious Infections
Incidence of grade ≥3 infections according to CTCAE v6.0
Lymphocyte Subpopulation Kinetics
Longitudinal assessment of B-cell, T-cell, and NK-cell populations in peripheral blood following CD19-directed CAR-T cell therapy
CAR-T Cell Expansion, Persistence, and Immunophenotype
Assessment of circulating CAR-T cell levels and immunophenotypic characteristics following infusion
Inflammatory Cytokine Kinetics
Longitudinal assessment of circulating inflammatory cytokine levels
Complement Recovery Kinetics
Changes in serum complement C3 and C4 levels following treatment
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University of Sao Paulo
Lead sponsor
Regional Blood Center of Ribeirao Preto
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
