A Phase I/II Open-label Study of the Safety and Efficacy of Epstein-Barr Virus Specific T-cell Lines for the Treatment of EBV Infection or EBV-related Lymphoproliferative Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment
研究概览
简要总结
This study evaluates the safety and efficacy of EBV-specific T-cell lines to treat patients suffering from high EBV viral titers not responding to standard of care therapies and to treat EBV-related lymphoma. The study will recruit 6 patients to receive autologous T cells or a T cell line derived from the patient's allogeneic donor (in the case of stem cell transplant recipients), and 6 patients to receive a T-cell line prepared from a matched or partially matched related donor.
详细描述
Epstein-Barr virus (EBV) is a member of the herpes virus family and infects up to 95% of individuals over their lifetime. Most initial infections occur in childhood and after a brief flu-like illness, the virus enters a phase of latency.
Patients who receive a bone marrow transplant or an organ transplant take medications drugs that weaken their immune systems. In these contexts, the virus can "reactivate" and cause very serious problems, such as lymphoma. For unknown reasons, people with a normal immune system can also develop lymphoma due to EBV.
The purpose of this study is to test the safety and efficacy of immune cells (T lymphocytes) that are specifically "taught" to recognize the virus-infected cells and to eliminate them. This "education" occurs is done over during a 2 weeks period (approximately), in the research laboratory. The cells are then transfused into the patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Capacity to provide informed consent
- •Age ≥ 18 years old
- •Confirmed treatment-refractory EBV reactivation or EBV-related lymphoma
- •ECOG of 2 or less
排除标准
- •Medical condition requiring a corticosteroid dose greater than Prednisone 0.5mg/kg/day (or equivalent) at the time of the infusion.
- •Patient has received T-cell depleting antibodies or stem cell transplantation in the 28 days prior to proposed date of anti-EBV T-cell line infusion
- •Patient has received a solid organ transplant in the 3 months prior to proposed date of anti-EBV T-cell line infusion.
- •Pregnant or nursing females
- •Life expectancy of less than 3 months due to a condition unrelated to the EBV- related disease.
- •Active uncontrolled GVHD
- •Active uncontrolled SOT rejection episode
- •DONOR ELIGIBILITY: An allogeneic donor must be a first-degree relative with at least 3/6 HLA compatibility, have consented to donate peripheral blood mononuclear cells, and fulfill the same criteria for stem cell donation according to the hospital's standard operating procedure.
研究组 & 干预措施
Autologous or allogenic (stem cell donor) T cells
Subjects receive an autologous anti-EBV T-cell line or a T-cell line derived from the patient's allogeneic (stem cell transplant) donor.
干预措施: Group A (Biological)
Allogeneic "third party" T cells
Subjects receive a T-cell line from a matched or partially matched related donor.
干预措施: Group B (Biological)
结局指标
主要结局
Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment
时间窗: During observation period (up to 42 days post infusion)
Complications: infusional toxicity, immune-related and other
次要结局
- Incidence/severity of graft-versus-host disease among patients who underwent stem cell transplantation(During observation period until 12 months post infusion)
- Number and severity of solid organ rejection episodes per patient among those who underwent solid organ transplant(During observation period until 12 months post infusion)
- Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas(During observation period until 12 months post infusion)
- Changes in EBV titers (viral load) for each patient(Until 12 months post infusion)
- Immune reconstitution as measured by various laboratory assays of immune cell type and function(During observation period until 12 months post infusion)
- Transplant-related outcomes(During observation period until 12 months post infusion)
- Incidence of primary disease relapse among patients who underwent stem cell transplantation(During observation period until 12 months post infusion)
- All cause mortality(At 12 months)
研究者
Dr. Jean-Sebastien Delisle, MD, PhD
Clinician-Scientist, Hematopoietic Cell Transplantation Program
Maisonneuve-Rosemont Hospital