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Safety of PiggyBac Transposon CAR T-cells Targeting CD-19 in Refractory Lupus.
Bu Faz 1 (Phase 1) klinik çalışma, standart bağışıklık baskılayıcı tedavilere yanıt vermemiş dirençli sistemik lupus eritematozus (systemic lupus erythematosus, SLE) hastalarında CD19'u hedefleyen PiggyBac transpozon aracılı CAR-T hücrelerinin güvenliliğini ve etkililiğini değerlendirmektedir. Çalışmaya, 18-60 yaş arasında ve SLE tanısı kabul görmüş sınıflandırma ölçütlerine (ACR 1997, SLICC veya Avrupa romatoloji birlikleri ölçütleri) göre konmuş kişiler alınmaktadır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Inclusion Criteria: 1. Age between 18 and 60 years. 2. Diagnosis of Systemic Lupus Erythematosus (SLE), as defined by the American College of Rheumatology (ACR) 1997 criteria, The Systemic Lupus International Collaborating Clinics (SLICC) criteria, or the European Alliance of Associations for Rheumatology (EULAR)/ACR classification. 3. Refractory SLE, defined by one or more of the following: 3.1 Persistently active SLE requiring ongoing maintenance therapy (if not contraindicated) with: * Antimalarial drug. * Either mycophenolate (minimum daily dose of 1500 mg) or azathioprine (minimum daily dose of 1.5 mg/kg). * Patients must also need a minimum daily dose of 7.5 mg prednisolone for lower disease activity maintenance, or have a SLEDAI score of 8 or higher. 3.2 Biopsy-proven proliferative lupus nephritis after two standard induction therapies, including intravenous cyclophosphamide (cumulative dose of at least 1.5 g) and mycophenolate mofetil (administered for a minimum of 3 months), unless contraindicated. 3.3 Worsening of biopsy-proven lupus nephritis (activity index \> 6 and chronicity index \< 6 within 6 months), indicated by increased proteinuria and/or decreased estimated glomerular filtration rate, despite treatment with high-dose corticosteroids (prednisolone at least 0.7 mg/kg/day or equivalent) and either mycophenolate mofetil or cyclophosphamide for a minimum of 14 days. 4. Ability to understand and willingness to sign a written informed consent document. 5. Participants of child-bearing or child-fathering potential must agree to practice birth control from enrollment until four months after receiving CAR T-cell infusion. Exclusion Criteria: 1. Pregnant or breastfeeding women. 2. History of active malignancy, excluding non-melanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast). 3. History of vital organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. 4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, cirrhosis, or psychiatric illness/social situations that limit compliance with study requirements. 5. Any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects or interfere with the research procedure, or the evaluation of safety and efficacy. 6. Serologic status indicating active HIV, hepatitis B, or C infection. Participants positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR prior to enrollment. 7. History of severe adverse drug reaction to Cyclophosphamide or Fludarabine. 8. Received a live vaccine within 30 days prior to CAR-T cell infusion. 9. eGFR CKD-EPI \< 30 ml/min/1.73m\^2. 10. Participation in other clinical investigations during the study period. 11. Prior receipt of CAR-T cell therapy outside this protocol.