mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- immunological response
研究概览
简要总结
- Rationale
Immunotherapy applying ex vivo generated and tumor antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Most of the successful results have been observed in patients with minimal residual disease, rather than patients with advanced metastatic disease. Moreover, the investigators' preliminary results show that presence of tumor epitope specific T cells in biopsies taken from delayed type hypersensitivity (DTH) reaction sites highly correlates with prolonged progression free survival (PFS).
Within uveal melanoma patients, a group with high risk of metastatic disease can be identified on basis of tumor specific genetic changes in loss of chromosome 3.
At present no standard adjuvant or systemic treatment is available. Applying DC-based immunotherapy in this group of high risk patients might reduce the risk of recurrence without interference in the current treatment guidelines. 2. Objectives
In this joint clinical study of Radboud University Nijmegen Medical Centre (RUNMC) and Rotterdam Eye Hospital, the investigators aim to determine the in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC. 3. Study design
This study is an open label non-randomized phase II intervention study. 4. Study population
The investigators' study population consists of HLA-A2 positive patients with a high risk uveal melanoma with proven expression of melanoma associated antigens tyrosinase and/or gp100. 5. Main study endpoints
This is an exploratory study aiming to demonstrate proof of principle. The first study endpoints are in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC, administered i.v./i.d. and toxicity. Secondary study endpoints are progression free survival, overall survival, and toxicity.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histological documented uveal melanoma
- •HLA-A2.1 phenotype (intervention arm)
- •non-HLA-A2.1 phenotype (control arm)
- •melanoma expressing gp100 and/or tyrosinase
- •high risk genetic profile (loss of chromosome 3) determined by FISH
- •interval since local treatment of uveal melanoma < 12 months
- •no signs of liver metastasis determined by diagnostic CT-abdomen
- •normal serum LDH
- •no signs of cerebral metastases
- •bilirubin < 25 micromol/l
- •WHO performance scale 0-1
- •age 18-75 years
- •written informed consent
- •expected adequacy of followup
- •no pregnant or lactating women
排除标准
- •history of second malignancy, except adequately treated basal cell carcinoma
- •serious active infections
- •autoimmune disease or organ allografts
- •concomitant use of immunosuppressive drugs
- •known allergy to shell-fish
研究组 & 干预措施
dendritic cell vaccination
HLA-A2.1 positive patient will receive 3 biweekly intradermal/intravenous vaccination with autologous mRNA transfected mature dendritic cells, followed by a DTH skin test for monitoring purposes. One such cycle is repeated every 6 months if no signs of progression, up to a total of 3 cycles.
干预措施: autologous dendritic cells electroporated with mRNA (Biological)
control arm
For comparison, HLA-A2.1 negative patients will be monitored for clinical response (secondary endpoint).
结局指标
主要结局
immunological response
时间窗: 2 years
次要结局
- clinical response (progression free survival)(5 years)