CD19-Directed CAR-T Cell Therapy in Refractory Systemic Lupus Erythematosus

NCT07659704 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: HEMO-03-CART
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lupus Erythematosus, Systemic

Keywords

Systemic Lupus Erythematosus; SLE; Refractory Systemic Lupus Erythematosus; Lupus Nephritis; CAR-T Cell Therapy; CD19-Directed CAR-T Cells; CD19; Chimeric Antigen Receptor T Cells; B Cell Depletion; B Lymphocytes; Autoimmune Diseases; Cellular Therapy; Advanced Therapy Medicinal Products; Immune Reconstitution; Autologous CAR-T Cells

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days after CAR-T cell infusion

Secondary Outcomes (15)

• Incidence of Grade ≥3 Cytopenias

  Up to 90 days after CAR-T cell infusion

• Time to Hematologic Recovery

  Up to 12 months after CAR-T cell infusion

• Incidence and Severity of Infections

  Up to 12 months after CAR-T cell infusion

• Incidence of Serious Infections

  Up to 12 months after CAR-T cell infusion

• Changes in Serum Immunoglobulin Levels

  Baseline, Day 30, Day 90, Day 180, and Day 360

Other Outcomes (6)

• Lymphocyte Subpopulation Kinetics

  Screening, pre-lymphodepletion, Day 0, Day 7, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360

• CAR-T Cell Expansion, Persistence, and Immunophenotype

  Pre-lymphodepletion, Day 3, Day 7, Day 10, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360

• Inflammatory Cytokine Kinetics

  Pre-lymphodepletion, Day 3, Day 7, Day 10, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360

Study Arms (1)

Autologous CD19-Directed CAR-T Cells

EXPERIMENTAL

Participants with refractory systemic lupus erythematosus will undergo leukapheresis for the manufacture of autologous CD19-directed CAR-T cells, followed by lymphodepleting chemotherapy and a single intravenous infusion of the CAR-T cell product.

Biological: Autologous CD19-Directed CAR-T Cells Manufactured at Ribeirão Preto Blood Center

Interventions

Autologous CD19-Directed CAR-T Cells Manufactured at Ribeirão Preto Blood Center BIOLOGICAL

Autologous 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.

Autologous CD19-Directed CAR-T Cells

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Adequate organ function, including:
• Hepatic function: AST and ALT ≤3× upper limit of normal (ULN); total bilirubin ≤2× ULN (participants with documented Gilbert syndrome are eligible).
• Hematologic function: neutrophils ≥1,000/mm³; hemoglobin ≥8 g/dL without transfusion within 14 days; lymphocytes ≥500/mm³; platelets ≥20,000/mm³ without transfusion within 14 days.
• Renal function: estimated creatinine clearance ≥30 mL/min (CKD-EPI).
• Cardiac function: left ventricular ejection fraction ≥40%.
• Pulmonary function: oxygen saturation ≥92% on room air.
• Women of childbearing potential must agree to use highly effective contraception during study participation and for 12 months after CAR-T cell infusion.
• Male participants must agree to use barrier contraception during study participation and for 12 months after CAR-T cell infusion.
• Ability to understand and provide written informed consent.

You may not qualify if:

• 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.
• History of malignancy within 2 years prior to screening, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, or stage I uterine cancer.
• Previous or suspected hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
• Active or uncontrolled bacterial, viral, fungal, or other infection.
• Active hepatitis B infection or detectable HBV DNA.
• Active hepatitis C infection or detectable HCV RNA.
• Human immunodeficiency virus (HIV) infection.
• Pregnancy, breastfeeding, or plans to become pregnant during the study or within 12 months after CAR-T cell infusion.
• Major surgery within 4 weeks prior to screening.
• Administration of a live attenuated vaccine within 4 weeks prior to screening.
• Prior allogeneic or autologous hematopoietic stem cell transplantation or prior solid organ transplantation.
• Inability or unwillingness to comply with study procedures and follow-up requirements.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Regional Blood Center of Ribeirao Preto: collaborator

Study Sites (2)

Hospital das Clinicas de Ribeirão Preto (HCFMRP-USP)

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP)

São Paulo, São Paulo, 05403-010, Brazil

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Diego V. Clé, MD, MBA, PhD

CONTACT

+55 16 21019300; terapia@hemocentro.fmrp.usp.br

Maria Carolina Oliveira Rodrigues, MD, PhD

CONTACT

mcarolor@usp.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MBA, PhD

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 22, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2)