A Randomized Phase II Trial to Evaluate an EBV Derived Dendritic Cell (DC) Vaccine When Administered Alone or Co-administered With the TLR9 Agonist, DUK-CPG-001, in EBV+ Lymphoma in the Setting of Autologous Stem Cell Transplant
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Immune response
研究概览
简要总结
This is a non-blinded, not placebo controlled, randomized, parallel phase 2 pilot study to evaluate the immunological response and the safety of Epstein Barr Virus (EBV)-derived tumor antigen, Latent Membrane Protein-2 (LMP2)-loaded dendritic cell (DC) vaccines alone or co-administered with the TLR9 ligand, DUK-CPG-001, in patients with EBV+ lymphoma in the setting of autologous stem cell transplant with infusion of mature T cells. Patients will be randomized to receive vaccine alone or vaccine co-administered with the TLR9 ligand, DUK-CPG-001. Randomization will be stratified by 2 disease types: Hodgkin lymphoma and non-Hodgkin lymphoma.
详细描述
Objectives
The primary objectives of this study are to:
- To assess the ability of an Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine co-administered with a Toll-like receptor 9 (TLR9) ligand, DUK-CPG-001, to induce EBV derived tumor antigen specific CD8+ T cell response in patients with EBV+ lymphoma in the setting of autologous stem cell transplant
- To assess the ability of an Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine administered alone to induce EBV derived tumor antigen specific CD8+ T cell response in patients with EBV+ lymphoma in the setting of autologous stem cell transplant
- To evaluate the safety of using LMP2- loaded DC vaccine alone or co-administered with the TLR9 ligand, DUK-CPG-001, in patients with EBV+ lymphoma in the setting of autologous stem cell transplant
The secondary objectives of this study are to:
- Evaluate duration of the presence of long term memory cells after administration of an LMP2 loaded DC vaccine alone or co-administered with the TLR9 ligand, DUK-CPG-001.
- Evaluate duration of multi-functional CD8 T cell responses after administration of an LMP2 loaded DC vaccine alone or co-administered with the TLR9 ligand, DUK-CPG-001.
- Evaluate duration of Th1, Th2 and Th17 CD4 T cell responses as well as CD4+CD25+Foxp3+ regulatory T cell (Treg) responses after administration of an LMP2 loaded DC vaccine alone or co-administered with the TLR9 ligand, DUK-CPG-001.
- Evaluate the disease free survival (DFS) of patients with EBV+ lymphoma in the setting of autologous stem cell transplant who receive LMP2-loaded DC vaccines alone or co-administered with DUK-CPG-001.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- 否
入选标准
- •Each patient must meet all of the following inclusion criteria:
- •Patient must have a histologically proven diagnosis of any EBV+ Hodgkin or non-Hodgkin lymphoma
- •EBV positive will be defined as positive if LMP1 or 2 or EBER are positive. As long as EBV positive on a prior biopsy, EBV testing will not be required at the time of relapse. However, if EBV testing performed on a more recent biopsy and it is negative, that patient will be excluded.
- •Patients must have had persistent, relapsed, or refractory disease to at least one prior regimen with plans to proceed to autologous stem cell transplant
- •Patients must be in a complete remission at time of initial pheresis for vaccine preparation; complete remission will be determined using Cheson Criteria100
- •There are no limits on the number of prior therapies allowed
- •Able to give voluntary written informed consent
- •Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study therapy and for 3 months after vaccine #
- •Male subject agrees to use an acceptable method for contraception for the duration of the study therapy and for 3 months after vaccine #
- •Patients must be 18 years of age or older.
- •ECOG performance status 0-2.
排除标准
- •An estimated or measured creatinine clearance of less than 30 ml/min.
- •AST, ALT, total bilirubin > 3 times the upper limit of normal
- •Patients on chronic immunosuppressive therapy for any reason (other than chemotherapy for HL)
- •Chronic systemic steroid therapy at doses greater than 10mg/day of prednisone or its equivalent.
- •Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result within 48 hours of enrollment. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Patient has received other investigational drugs for this disease within 14 days of enrollment
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Patients who are HIV positive AND have a CD4 count <50
- •Prior solid organ transplant or allogeneic stem cell transplant
研究组 & 干预措施
LMP2A-loaded conventional DC vaccine
Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine
干预措施: LMP2A-loaded conventional DC vaccine (Biological)
LMP2A-loaded DC vaccine + DUK-CPG-001
Epstein-Barr virus (EBV) derived tumor antigen, LMP2 loaded DC vaccine co-administered with a Toll-like receptor 9 (TLR9) ligand, DUK-CPG-001
干预措施: DUK-CPG-001 (Biological)
结局指标
主要结局
Immune response
时间窗: 7 days post 2nd vaccination
Immune response will be defined as an increase in number of spots to 25-fold more than at baseline, and at least 200 spots per 105 cluster of differentiation 8 (CD8)+ T cells, by Day 7 post 2nd vaccination (i.e., a patient with a baseline of 1 spot/105 CD8+ T cells who achieved 25 spots/million would not be counted as a response). "Spots" are the readout for immune activation measured by the enzyme-linked immunosorbent spot (ELISPOT) assay. Each spot is indicative of an activated T cell that secrete interferon (IFN)-gamma, a cytokine produced by activated T cells.
次要结局
- Duration of multi-functional CD8 T cell responses(7 days post second dose of vaccine)
- Duration of Th1, Th2 and Th17 cluster of differentiation 4 (CD4) T cell responses as well as CD4+cluster of differentiation 25 (CD25)+Foxp3+ regulatory T cell (Treg) responses(7 days post second dose of vaccine)
- Number of patients with greater than grade 1 toxicity(30 days post last dose of vaccine)
- Duration of the presence of long term memory cells(7 days post second dose of vaccine)
- Disease free survival(up to 10 years)
研究者
David Rizzieri, MD
Professor of Medicine
Duke University