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CD19-Directed CAR-T Cell Therapy in Refractory Systemic Lupus Erythematosus (CLEVER-SLE)

2026年6月15日 更新者：Diego Villa Clé、University of Sao Paulo

CD19-targeted Lymphocyte Engineering Validation for the trEatment of Refractory Systemic Lupus Erythematosus

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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease characterized by loss of immune tolerance, production of pathogenic autoantibodies, and immune-mediated tissue injury. The disease can affect virtually any organ system, including the skin, joints, kidneys, hematologic system, cardiovascular system, and central nervous system. Despite major advances in the understanding of disease pathogenesis and the availability of immunosuppressive and biologic therapies, many patients continue to experience persistent disease activity, recurrent flares, progressive organ damage, reduced quality of life, and increased mortality.

B lymphocytes play a central role in the pathogenesis of SLE. Beyond their ability to differentiate into antibody-producing plasma cells, B cells contribute to disease development through antigen presentation, cytokine production, and maintenance of autoreactive immune responses. The persistence of autoreactive B-cell populations is believed to be a key driver of chronic disease activity and treatment resistance.

Several therapeutic strategies targeting B cells have been developed for SLE, including anti-CD20 monoclonal antibodies and inhibitors of B-cell survival pathways. Although these approaches have improved outcomes for many patients, a substantial proportion of individuals fail to achieve sustained remission. One potential limitation of antibody-based therapies is their inability to completely eliminate autoreactive B-cell populations residing within inflamed tissues and specialized immune niches. In contrast, CD19-directed CAR-T cells are living immune effectors capable of expanding in vivo, trafficking to affected tissues, and mediating deep depletion of B cells not only in the peripheral blood but also within sites of ongoing autoimmune inflammation. This broader and more profound tissue-level B-cell depletion may contribute to more durable disease control and potentially restore immune tolerance. In addition, existing therapies often require continuous administration and may be associated with cumulative toxicities, incomplete disease control, or relapse after treatment discontinuation.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy represents a novel therapeutic strategy that enables a patient's own T lymphocytes to recognize and eliminate CD19-expressing B cells. This approach has demonstrated unprecedented efficacy in B-cell malignancies and has transformed the treatment landscape of several hematologic cancers. More recently, emerging clinical evidence has suggested that deep B-cell depletion induced by CD19-directed CAR-T cells may also be capable of resetting abnormal immune responses in autoimmune diseases.

Early clinical experiences in patients with severe refractory autoimmune diseases, including systemic lupus erythematosus, have reported rapid and profound reductions in disease activity, sustained clinical remissions, normalization of serological markers, and significant reductions in the need for immunosuppressive medications. These findings have generated considerable interest in the potential application of CAR-T cell therapy beyond oncology and have established a strong scientific rationale for further investigation in autoimmune disorders.

The CAR-T product evaluated in this study consists of autologous T lymphocytes genetically modified to express a chimeric antigen receptor directed against CD19. The product is manufactured at the Ribeirão Preto Blood Center (Hemocentro de Ribeirão Preto), one of the leading academic cell therapy centers in Brazil. This manufacturing platform has previously demonstrated feasibility, safety, and clinical activity in patients with hematologic malignancies and serves as the foundation for the present investigation.

The CLEVER-SLE study was developed to evaluate the use of CD19-directed CAR-T cell therapy manufactured at the Ribeirão Preto Blood Center in patients with refractory systemic lupus erythematosus. The study seeks to expand current knowledge regarding the safety profile and therapeutic potential of CAR-T cells in autoimmune diseases while generating clinical evidence to support the development of advanced cellular therapies for patients with severe disease who have limited treatment options.

By investigating a strategy capable of directly targeting the cellular drivers of autoimmunity, this study aims to contribute to the development of transformative therapies that may achieve sustained disease control and improve long-term outcomes for patients with refractory SLE.

研究の種類

介入

入学 (推定)

16

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

  • 名前：Maria Carolina Oliveira Rodrigues, MD, PhD
  • メール：mcarolor@usp.br

研究場所

  • ブラジル
    • São Paulo
      • Ribeirão Preto、São Paulo、ブラジル、14048-900
        • Hospital das Clinicas de Ribeirão Preto (HCFMRP-USP)
        • コンタクト：
        • コンタクト：
      • São Paulo、São Paulo、ブラジル、05403-010
        • Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP)
        • コンタクト：
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Any medical condition that, in the investigator's judgment, could compromise participant safety or interfere with study assessments.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Autologous CD19-Directed CAR-T Cells
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.
生物学的：Autologous CD19-Directed CAR-T Cells Manufactured at Ribeirão Preto Blood Center
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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Incidence and Severity of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
時間枠：30 days after CAR-T cell infusion
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

二次結果の測定

結果測定
メジャーの説明
時間枠
Incidence of Grade ≥3 Cytopenias
時間枠：Up to 90 days after CAR-T cell infusion
Incidence of grade ≥3 anemia, neutropenia, lymphopenia, and thrombocytopenia according to CTCAE v6.0.
Up to 90 days after CAR-T cell infusion
Time to Hematologic Recovery
時間枠：Up to 12 months after CAR-T cell infusion
Time to resolution of cytopenias to grade <1.
Up to 12 months after CAR-T cell infusion
Incidence and Severity of Infections
時間枠：Up to 12 months after CAR-T cell infusion
Cumulative incidence and severity of infections
Up to 12 months after CAR-T cell infusion
Incidence of Serious Infections
時間枠：Up to 12 months after CAR-T cell infusion
Incidence of grade ≥3 infections according to CTCAE v6.0
Up to 12 months after CAR-T cell infusion
Changes in Serum Immunoglobulin Levels
時間枠：Baseline, Day 30, Day 90, Day 180, and Day 360
Absolute and relative changes in serum IgG, IgA, and IgM concentrations compared with baseline
Baseline, Day 30, Day 90, Day 180, and Day 360
Incidence of Other CAR-T Cell-Associated Toxicities
時間枠：Up to 12 months after CAR-T cell infusion
Incidence and severity of coagulopathy, immune effector cell-associated hemophagocytic syndrome (IEC-HS), cytomegalovirus reactivation, and local immune effector cell-associated toxicity syndrome (LICATS)
Up to 12 months after CAR-T cell infusion
Deep Remission Rate
時間枠：6 months after CAR-T cell infusion
Percentage of participants achieving deep remission, defined as clinical SLEDAI-2K=0 (allowing isolated serological activity), Physician Global Assessment (PGA) ≤0.5, and no requirement for additional immunosuppressants, biologics, small molecules, or corticosteroids after CAR-T cell therapy.
6 months after CAR-T cell infusion
SRI-4 Response Rate
時間枠：6 months after CAR-T cell infusion
Percentage of participants achieving an SRI-4 response, defined as a ≥4-point reduction in SLEDAI-2K score, no new BILAG A score and no more than one new BILAG B score, and no worsening in PGA (increase <0.3 points)
6 months after CAR-T cell infusion
Lupus Low Disease Activity State (LLDAS) Achievement Rate
時間枠：6 and 12 months after CAR-T cell infusion
Percentage of participants achieving LLDAS criteria
6 and 12 months after CAR-T cell infusion
DORIS Remission Rate
時間枠：6 and 12 months after CAR-T cell infusion
Percentage of participants achieving Definitions Of Remission In SLE (DORIS) criteria
6 and 12 months after CAR-T cell infusion
Renal Response Rate
時間枠：6 and 12 months after CAR-T cell infusion
Among participants with active lupus nephritis (proteinuria ≥500 mg/24 hours at baseline), percentage achieving complete renal response or partial renal response
6 and 12 months after CAR-T cell infusion
Cutaneous Lupus Response Rate
時間枠：6 and 12 months after CAR-T cell infusion
Among participants with baseline CLASI-Activity score ≥10, percentage achieving CLASI-50 response, defined as ≥50% reduction in CLASI-Activity score from baseline.
6 and 12 months after CAR-T cell infusion
Articular Response Rate
時間枠：6 and 12 months after CAR-T cell infusion
Among participants with ≥6 active arthritic joints at baseline, percentage achieving at least 50% reduction in the number of active joints
6 and 12 months after CAR-T cell infusion
Anti-dsDNA Serologic Response
時間枠：6 and 12 months after CAR-T cell infusion
Percentage of participants achieving negative anti-double-stranded DNA antibody titers (negative or ≤1:10)
6 and 12 months after CAR-T cell infusion
Corticosteroid and Immunosuppressant-Free Remission
時間枠：6 and 12 months after CAR-T cell infusion
Percentage of participants not receiving corticosteroids or immunosuppressive medications
6 and 12 months after CAR-T cell infusion

その他の成果指標

結果測定
メジャーの説明
時間枠
Lymphocyte Subpopulation Kinetics
時間枠：Screening, pre-lymphodepletion, Day 0, Day 7, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360
Longitudinal assessment of B-cell, T-cell, and NK-cell populations in peripheral blood following CD19-directed CAR-T cell therapy
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
時間枠：Pre-lymphodepletion, Day 3, Day 7, Day 10, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360
Assessment of circulating CAR-T cell levels and immunophenotypic characteristics following infusion
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
時間枠：Pre-lymphodepletion, Day 3, Day 7, Day 10, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360
Longitudinal assessment of circulating inflammatory cytokine levels
Pre-lymphodepletion, Day 3, Day 7, Day 10, Day 17, Day 24, Day 30, Day 60, Day 90, Day 180, and Day 360
Complement Recovery Kinetics
時間枠：Screening, pre-lymphodepletion, Day 30, Day 60, Day 90, Day 180, and Day 360
Changes in serum complement C3 and C4 levels following treatment
Screening, pre-lymphodepletion, Day 30, Day 60, Day 90, Day 180, and Day 360
Vaccine Antibody Titers
時間枠：Pre-lymphodepletion, Day 30, Day 60, Day 90, Day 180, and Day 360
Changes in antibody titers against measles and diphtheria-tetanus vaccination antigens
Pre-lymphodepletion, Day 30, Day 60, Day 90, Day 180, and Day 360
NETosis Biomarkers
時間枠：Screening, Day 30, Day 60, Day 90, Day 180, and Day 360
Changes in peripheral blood markers associated with neutrophil extracellular trap (NET) formation and NETosis
Screening, Day 30, Day 60, Day 90, Day 180, and Day 360

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University of Sao Paulo

協力者

Regional Blood Center of Ribeirao Preto

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年10月1日

一次修了 (推定)

2027年10月1日

研究の完了 (推定)

2028年10月1日

試験登録日

最初に提出

2026年6月15日

QC基準を満たした最初の提出物

2026年6月15日

最初の投稿 (実際)

2026年6月22日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月22日

QC基準を満たした最後の更新が送信されました

2026年6月15日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • HEMO-03-CART

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

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