CD19 CAR-T Therapy for Refractory Childhood-Onset Systemic Lupus Erythematosus
A Clinical Study of CD19 Chimeric Antigen Receptor T-Cell Therapy for Patients With Refractory Childhood-Onset Systemic Lupus Erythematosus
This study is evaluating the safety and potential benefits of CD19 chimeric antigen receptor T-cell (CAR-T) therapy in children and young adults with severe systemic lupus erythematosus (SLE) that began during childhood. The study will include up to 8 participants aged 25 years or younger whose disease remains active despite treatment with multiple immune-suppressing medicines and has affected at least one major organ.
CAR-T cells will be made from each participant's own T cells and modified to recognize CD19, a protein found on B cells that contribute to SLE. Participants will receive chemotherapy to reduce existing immune cells, followed by a single intravenous infusion of SNUH-CD19-CAR-T cells. They will be monitored for side effects and changes in disease activity, organ involvement, laboratory findings, and the need for steroids or other immune-suppressing medicines. The main assessment will be performed 1 year after the CAR-T cell infusion.
Studienübersicht
Status
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: Hye Ji, CRC
- Telefonnummer: 82-10-2957-8895
- E-Mail: hyeji91@snu.ac.kr
Studienorte
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Seoul, Südkorea
- Rekrutierung
- Seoul National University Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
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Participants must be 25 years of age or younger at the time of SNUH-CD19-CAR-T infusion.
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Participants must have a diagnosis of systemic lupus erythematosus and meet the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for systemic lupus erythematosus.
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Participants must be currently receiving or have previously received at least three of the following therapies, including corticosteroids: hydroxychloroquine, methotrexate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, rituximab, or belimumab.
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Participants must have involvement of at least one of the following major organ systems:
- Kidney: class II-V lupus nephritis confirmed by biopsy or proteinuria greater than 0.5 g/day
- Heart: pericarditis, myocarditis, conduction abnormality, or valvular disease
- Lung: pleuritis, interstitial lung disease, or pulmonary arterial hypertension
- Hematologic system: platelet count below 50,000/μL or hemolytic anemia
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Participants must have uncontrolled active disease, defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 10 or higher.
Exclusion Criteria:
- Severe active central nervous system lupus requiring current treatment, including uncontrolled seizures, psychotic symptoms, or cognitive impairment.
- Inability to obtain an adequate leukapheresis product suitable for the manufacture of SNUH-CD19-CAR-T cells.
- Known human immunodeficiency virus infection.
- Uncontrolled active infection, as determined by the investigator. An infection will be considered controlled if appropriate treatment has been administered and there is no evidence of progression at enrollment. Persistent fever without other signs or symptoms of infection will not, by itself, be considered evidence of progressive infection.
- Pregnancy or breastfeeding.
- Any medical or other condition that, in the investigator's clinical judgment, makes participation in the study inappropriate.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: SNUH-CD19-CAR-T Treatment
Participants will receive protocol-defined lymphodepleting chemotherapy followed by a single intravenous infusion of autologous SNUH-CD19-CAR-T cells at a dose of 0.2 to 1.0 × 10^6 CAR-positive viable T cells/kg. |
Autologous T cells genetically modified to express a CD19-targeted chimeric antigen receptor. Participants will receive a single intravenous infusion at a dose of 0.2 to 1.0 × 10^6 CAR-positive viable T cells/kg. Participants will receive protocol-defined lymphodepleting chemotherapy before CAR-T cell infusion. The preferred regimen consists of intravenous fludarabine 30 mg/m²/day for 4 days and cyclophosphamide 500 mg/m²/day for 2 days. Alternative regimens, dose reduction, partial administration, or omission may be used according to the protocol and the investigator's clinical judgment |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
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Proportion of Participants Achieving Lupus Low Disease Activity State
Zeitfenster: 1 year after SNUH-CD19-CAR-T infusion
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1 year after SNUH-CD19-CAR-T infusion
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Proportion of Participants With Lupus Nephritis Achieving a Renal Response
Zeitfenster: 1 year after SNUH-CD19-CAR-T infusion
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Among participants with lupus nephritis at baseline, renal response is defined as achievement of either a complete or partial renal response according to protocol-specified criteria. Complete renal response requires eGFR ≥90 mL/min/1.73 m² or ≥90% of baseline, urine protein-to-creatinine ratio <0.5 g/g, normal or inactive urinary sediment, and normal serum creatinine or a value within 15% of baseline. Partial renal response requires eGFR ≥80% of baseline or an improvement of ≥25%, a ≥50% reduction in urine protein-to-creatinine ratio to <3.0 g/g, and serum creatinine ≤125% of baseline. |
1 year after SNUH-CD19-CAR-T infusion
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Mitarbeiter und Ermittler
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
- Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- SNUH-CD19-CART-SLE-01
Plan für individuelle Teilnehmerdaten (IPD)
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Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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