Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

Официальное название

Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

Обзор

This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection

Подробное описание

Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). In this prospective study, HLA-A\*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.

Вмешательства

• Биопрепарат EBV-TCR-T cells
  The patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg EBV-TCR-T cells per dose.

Первичные конечные точки

• Adverse events [Срок оценки: 1 year after EBV-TCR-T treatment]

Вторичные конечные точки (9)

• Dose-limiting toxicity (DLT) [Срок оценки: 28 days after EBV-TCR-T treatment]
• Maximum tolerated dose （MTD） [Срок оценки: 28 days after EBV-TCR-T treatment]
• The proportion of EBV-DNA negative patients [Срок оценки: 180 days after EBV-TCR-T treatment]
• The time to EBV-DNA negative [Срок оценки: 180 days after EBV-TCR-T treatment]
• Changes of EBV-DNA copies number [Срок оценки: 1 year after EBV-TCR-T treatment]
• Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells [Срок оценки: 28 days after EBV-TCR-T treatment]
• Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells [Срок оценки: 28 days after EBV-TCR-T treatment]
• Time to peak (Tmax) of EBV-TCR-T cells [Срок оценки: 28 days after EBV-TCR-T treatment]
• Half life time (T1/2) of EBV-TCR-T cells [Срок оценки: 28 days after EBV-TCR-T treatment]

Критерии участия

Критерии включения

• Age 1-60 years, gender unlimited.
• Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
• Fully understood and informed the study and signed the ICF.
• Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
• TCRT-T cell donor inclusion criteria: 1)Age >=8 years, gender unlimited; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8\~4) × 10\^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.

Критерии исключения

• Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
• Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV or left ventricular ejection fraction<50%) one week before TCR-T cell infusion.
• Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
• Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
• Have tumours, active and uncontrolled malignant diseases.
• Serologically positive for HIV-Ab or TAP-ab.
• Pregnant or lactating women.
• Men and their partners or women of childbearing potential refused contraception during the study period.
• Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
• Participated in any other clinical study of drugs and medical devices before 4 weeks of enrollment.
• Allergy to albumin.
• TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.

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

• Chinese PLA General Hospital — Пекин

Идентификаторы

NCT: NCT06135922 · S2022-381-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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