UCAR T-cell Therapy Targeting CD19/ BCMA in Patients With Relapse/ Refractory Autoimmune Diseases

Официальное название

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapse/Refractory Autoimmune Diseases

Обзор

This is an investigator-initiated trial to evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in With Relapse/Refractory Autoimmune Diseases.

Подробное описание

This is an investigator-initiated trial to evaluate the safety and efficacy ofuniversal allogeneic anti-CD19/BCMA CAR T-cells in Patients With Relapse/Refractory Autoimmune Diseases.

Study intervention consists of a single infusion of universal allogeneic CART-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Вмешательства

• Биопрепарат universal allogeneic anti-CD19/BCMA CAR T-cells
  A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells

Первичные конечные точки

• The number and severity of dose-limiting toxicity (DLT) events [Срок оценки: Within 28 Days After UCAR T-cell Infusion]
• The total number, incidence, and severity of AEs [Срок оценки: Up to 90 days After UCAR T-cell Infusion]

Вторичные конечные точки (9)

• AIHA：Rates of CR, CRi, PR, ORR [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• SLE：SLE Response Index 4 (SRI-4) [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• SLE: Change in the Systemic Lupus Erythematosus Disease Activity Index(SLEDAI) from baseline [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• SSc：Change in the modified Rodnan Skin Score (mRSS) from baseline [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• IIM：The ACR-EULAR Myositis Response Criteria [Total Improvement Score (TIS)] [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• AAV: Change in disease activity as measured by Birmingham Vasculitis Activity Score (BVAS) [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• IgG4-RD:IgG4-Related Disease Responder Index (IgG4-RD RI) [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• MG:Changes of Myasthenia Gravis Activities of Daily Living (MG-ADL) Score [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]
• MG:Quantitative Myasthenia Gravis Score (QMG) [Срок оценки: Up to 24 Months After UCAR T-cell Infusion]

Критерии участия

Критерии включения

• 1.Age ≥ 18 years old (inclusive), regardless of gender.
• 2.Positive expression of CD19 on peripheral blood B cells confirmed by flow cytometry.
• 3.Functional requirements for major organs are as follows:

• Bone marrow function must meet: A. Neutrophil count ≥ 0.5×10 \^ 9/L (no colony-stimulating factor treatment within 2 weeks before examination); B. Hemoglobin ≥ 60g/L; C. Platelets ≥ 30 × 10 \^ 9/L.
• Liver function: Alanine aminotransferase (ALT) ≤ 3×ULN (excluding ALT elevation due to inflammatory myopathy), aspartate aminotransferase (AST)≤3×Upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy), TBIL≤1.5×ULN (or ≤ 3.0×ULN for subjects with Gilbert syndrome);
• Renal function: creatinine clearance rate (CrCl) ≥ 30ml/minute (calculated by Cockcroft/Gault formula, acute CrCl decrease due to the target disease is excluded; LN is exluded);
• 4.ECOG score 0-1.
• 5.Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• 6.Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• 7.Subjects with relapsed or refractory autoimmune diseases, Including relapsed or refractory Autoimmune Hemolytic Anemia, relapsed or refractory Systemic Lupus Erythematosus, relapsed or refractory or Progressive Systemic Sclerosis, relapsed or refractory or Progressive Inflammatory Myopathy, relapsed or refractory ANCA-Associated Vasculitis, relapsed or refractory Immunoglobulin-G4 related disease and relapsed or refractory Myasthenia Gravis.

Критерии исключения

• 1.Subjects with a history of severe drug allergies or allergic constitutions;
• 2\. Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections;
• 3\. Subjects with insufficient cardiac function;
• 4\. Subjects with congenital immunoglobulin deficiencies;
• 5\. Subjects with a history of malignant tumors within the past five years, except for the following conditions: non-melanoma skin cancer, stage I tumors with a low recurrence probability after complete resection, clinically localized prostate cancer after treatment, cervical carcinoma in situ confirmed by biopsy or squamous intraepithelial lesion shown by smear, and stable papillary thyroid carcinoma or follicular thyroid carcinoma.
• 6\. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA >ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing;
• 7\. Subjects with mental illness and severe cognitive dysfunction;
• 8\. Pregnant women or women planning to conceive;
• 9.Subjects whom the investigator believes have other reasons that make them unsuitable for inclusion in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Changzhou No.2 People's Hospital — Changzhou

Идентификаторы

NCT: NCT06978738 · QH-CE-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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