Exploratory Clinical Study of EBV-AST Cell Injection for the Treatment of EBV-Associated Lymphoproliferative Disorders
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Karnofsky Performance Status (KPS) ≥
- •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.
排除标准
- •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.
研究组 & 干预措施
EBV-AST Cell Injection
Participants with EBV-associated lymphoproliferative disorders (including PTLD and EBV-positive lymphomas) will receive EBV-AST cell injection by intravenous infusion in a dose-escalation scheme. EBV-AST is administered every 2 weeks for up to 3 infusions (Day 0, Day 14, and Day 28). Three dose levels are planned: 3×10^5, 3×10^6, and 3×10^7 cells/kg per infusion, with dose-escalation decisions based on safety and protocol-defined criteria.
干预措施: EBV-AST Cell Injection (Biological)
结局指标
主要结局
Dose-Limiting Toxicities (DLTs)
时间窗: From first infusion (Day 0) through Day 28
Number of participants experiencing dose-limiting toxicities (DLTs) within 28 days after the first EBV-AST cell infusion, as defined by protocol-specific criteria and graded according to NCI CTCAE v5.0.
Safety: Incidence of Adverse Events
时间窗: From first infusion (Day 0) through 12 months after first infusion
Number of participants with treatment-emergent adverse events (AEs), immune-related adverse events (irAEs), and serious adverse events (SAEs), graded according to NCI CTCAE v5.0, including clinically significant laboratory abnormalities.
Recommended/Optimal Biologically Active Dose (OBD)
时间窗: Up to 28 days after first infusion for DLT evaluation; overall dose decision through study completion
Recommended/optimal biologically active dose (OBD) of EBV-AST, determined based on the incidence of DLTs, overall safety profile, and tolerability across dose levels.
次要结局
- Time to EBV-DNA Negativity(From first infusion (Day 0) through 12 months after first infusion)
- Objective Response Rate (ORR)(From first infusion (Day 0) through 12 months after first infusion)
- Change in EBV-DNA Level(From baseline through 12 months after first infusion)
- Disease Control Rate (DCR)(From first infusion (Day 0) through 12 months after first infusion)
- Progression-Free Survival (PFS)(From first infusion (Day 0) through 12 months after first infusion)
- Overall Survival (OS)(From first infusion (Day 0) through 12 months after first infusion)
- Duration of Response (DOR)(From first documented response through 12 months after first infusion)
- EBV-DNA Negativity Rate(From first infusion (Day 0) through 12 months after first infusion)
- Maximum Concentration (Cmax) of EBV-AST Cells in Peripheral Blood(From first infusion (Day 0) through Day 28)
- Concentration of EBV-AST Cells in Peripheral Blood (Cmax)(From baseline through Day 28 after first infusion)
研究者
Daihong Liu
Director, Department of Hematology
Chinese PLA General Hospital