EBV-AST Cell Injection for EBV-Associated Lymphoproliferative Disorders

Официальное название

Exploratory Clinical Study of EBV-AST Cell Injection for the Treatment of EBV-Associated Lymphoproliferative Disorders

Обзор

This is an investigator-initiated, open-label, single-arm, dose-escalation exploratory study to evaluate the safety, tolerability, and preliminary efficacy of EBV-AST cell injection in adults with EBV-associated lymphoproliferative disorders, including post-transplant lymphoproliferative disease (PTLD) and EBV-positive lymphomas. Participants will receive EBV-AST cell infusions intravenously every 2 weeks for up to 3 infusions at escalating dose levels. The primary objective is to assess safety and determine a potential optimal biologically active dose. Secondary objectives include preliminary tumor response and EBV-related virologic outcomes, as well as cellular PK/PD.

Подробное описание

EBV-associated lymphoproliferative disorders (LPD), including PTLD and EBV-positive lymphomas, are clinically challenging and may occur in immunocompromised or heavily treated patients. EBV-AST is a cellular immunotherapy consisting of EBV antigen-specific cytotoxic T lymphocytes generated by ex vivo stimulation and expansion of T cells using antigen peptide-loaded dendritic cells. After infusion, EBV-AST cells are expected to recognize and eliminate EBV-infected or EBV-antigen-expressing target cells and provide EBV-specific immune reconstitution.

This investigator-initiated, open-label, single-arm exploratory study uses a dose-escalation design to evaluate EBV-AST cell injection in adults with EBV-associated LPD. Approximately 4-18 participants will be enrolled across three dose levels (3×10\^5, 3×10\^6, and 3×10\^7 cells/kg per infusion). EBV-AST will be administered by intravenous infusion every 2 weeks for up to three infusions, following protocol-defined escalation rules and DLT assessment within 28 days after the first infusion. Participants will be monitored for adverse events and immune-related toxicities, and assessed for preliminary efficacy (tumor response and EBV-DNA/virologic outcomes) and cellular PK/PD.

Вмешательства

• Биопрепарат EBV-AST Cell Injection
  EBV-AST is an Epstein-Barr virus (EBV) antigen-specific cytotoxic T-lymphocyte product generated by ex vivo stimulation and expansion of T cells using peptide-loaded dendritic cells. EBV-AST is administered by intravenous infusion every 2 weeks for up to 3 infusions at escalating dose levels (3×10\^5, 3×10\^6, or 3×10\^7 cells/kg per infusion), according to the protocol-defined dose-escalation design.

Первичные конечные точки

• Dose-Limiting Toxicities (DLTs) [Срок оценки: From first infusion (Day 0) through Day 28]
• Safety: Incidence of Adverse Events [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Recommended/Optimal Biologically Active Dose (OBD) [Срок оценки: Up to 28 days after first infusion for DLT evaluation; overall dose decision through study completion]

Вторичные конечные точки (10)

• Objective Response Rate (ORR) [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Disease Control Rate (DCR) [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Progression-Free Survival (PFS) [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Overall Survival (OS) [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Duration of Response (DOR) [Срок оценки: From first documented response through 12 months after first infusion]
• EBV-DNA Negativity Rate [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Time to EBV-DNA Negativity [Срок оценки: From first infusion (Day 0) through 12 months after first infusion]
• Change in EBV-DNA Level [Срок оценки: From baseline through 12 months after first infusion]
• Maximum Concentration (Cmax) of EBV-AST Cells in Peripheral Blood [Срок оценки: From first infusion (Day 0) through Day 28]
• Concentration of EBV-AST Cells in Peripheral Blood (Cmax) [Срок оценки: From baseline through Day 28 after first infusion]

Критерии участия

Критерии включения

• Able to understand and voluntarily sign written informed consent.
• Age 18 to 75 years, inclusive.
• HLA genotype matches at least one of the following: HLA-A02:01, HLA-A11:01, or HLA-A\*24:02.
• Karnofsky Performance Status (KPS) ≥ 70.
• Life expectancy ≥ 3 months.
• Diagnosed with EBV-associated lymphoproliferative disorders, including:
• EBV infection-associated post-transplant lymphoproliferative disorder (PTLD) that is relapsed/refractory after at least first-line standard therapy; or
• EBV-associated lymphoma confirmed by histology and/or cytology with EBER positivity (ISH/FISH), with no standard treatment available or not suitable for standard therapy, including but not limited to: EBV-positive DLBCL, EBV-positive NK/T-cell lymphoma, EBV-positive Hodgkin lymphoma, EBV-positive Burkitt lymphoma, EBV-positive nodal TFH lymphoma (AITL type), and EBV-positive primary cutaneous T-cell lymphoma, meeting protocol-defined relapsed/refractory criteria.
• Absolute lymphocyte count ≥ 0.8 × 10\^9/L (except for PTLD participants).
• Adequate organ and bone marrow function per protocol-defined criteria.
• Participants of childbearing potential agree to use highly effective contraception throughout the study; women of childbearing potential must have a negative pregnancy test at screening.

Критерии исключения

• Known hypersensitivity to the investigational product or its components.
• Uncontrolled active graft-versus-host disease (GVHD) in PTLD participants.
• Known primary immunodeficiency disorders (e.g., X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, chronic granulomatous disease, hyper-IgE syndrome).
• Severe uncontrolled medical conditions that, in the investigator's judgment, make the participant unsuitable for enrollment.
• Serious cardiac disease within 6 months prior to first infusion (e.g., myocardial infarction, severe/unstable angina, bypass surgery, NYHA class III-IV heart failure).
• Chronic diseases requiring systemic immunosuppressants or systemic steroids (except local/inhaled steroids or physiologic replacement therapy).
• History of other malignancy within the past 5 years, except carcinoma in situ (e.g., cervix, bladder, breast) or non-melanoma skin cancer.
• Receipt of lymphocyte-based immunotherapy (e.g., CIK, DC, DC-CIK, LAK) within 3 months prior to consent.
• Receipt of interferon or other targeted immunodeficiency drugs within 3 months prior to consent; prior high-dose IL-2 therapy.
• Anti-cancer therapy within 14 days prior to consent (including chemotherapy or immunosuppressants/steroids); other cell therapy or live vaccines/attenuated vaccines or other investigational drugs within 28 days prior to consent; curative radiotherapy or major surgery within 4 weeks, or palliative local radiotherapy within 2 weeks prior to consent.
• Prior immune therapy-associated ≥ Grade 3 immune-related adverse events (irAEs).
• Unresolved toxicity from prior therapy > Grade 1 (except alopecia any grade; peripheral sensory neuropathy ≤ Grade 2).
• Uncontrolled psychiatric or neurologic disorders; drug abuse or alcohol dependence.
• Positive HIV antibody; positive Treponema pallidum antibody; active hepatitis B (HBsAg and/or HBeAg positive with HBV-DNA above ULN) or active hepatitis C (HCV-Ab positive and HCV-RNA positive).
• Uncontrolled severe active infection or contagious disease (excluding EBV infection).
• Pregnant or breastfeeding women.

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: NCT07450391 · S2025-726-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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