Active Immunization of Patients With Stage III and IV Melanoma in Whom a Regional Lymph Node Dissection is Planned, With Peptide-Pulsed Dendritic Cells: Evaluation of in Vivo Immune and Clinical Response and Migration
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Immune response
研究概览
简要总结
Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients, and both immunological and clinical responses have been observed. For these therapies accurate delivery to target organs is essential. Correct delivery and subsequent migration of vaccinated DCs to regional lymph nodes is of paramount importance for effective stimulation of the immune system. Currently it is not known what the best route of administration is for DC vaccines.
Using magnetically labeled DCs, we investigate the potential of MRI cell tracking to monitor DC therapy. This is investigated in stage III/IV melanoma patients in whom a regional lymph node dissection is scheduled. Autologous monocyte-derived DCs are labeled with the clinically approved superparamagnetic iron oxide (SPIO) formulation Endorem and 111In-oxine and injected either in the skin or directly in lymph nodes under ultrasound guidance. Two days after vaccination patients are monitored with scintigraphy and MR imaging. Lymph nodes are then resected. Subsequently patients receive 3 more vaccination with DCs. During and after therapy immune responses against the used melanoma peptides are monitored.
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
- •Histologically documented evidence of melanoma
- •Stage III-IV melanoma according to the 2001 AJCC criteria
- •Radical lymph node dissection planned, either with curative (stage III) or palliative (stage IV) intent
- •Melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory)
- •HLA-A2.1 phenotype according to lymphocyte HLA typing
- •ECOG performance status 0-1, life expectancy > 3 months
- •Age 18-75 years
- •Interval since last prior chemotherapy, immunotherapy or radiotherapy at least 4 weeks, no residual toxicity of prior treatment.
- •WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l
- •Written informed consent
- •Expected adequacy of follow-up
排除标准
- •No clinical signs of CNS metastases, in patients with a clinical suspicion of other metastases diagnostic tests should be performed to exclude this.
- •No concomitant use of corticosteroids or other immunosuppressive agents
- •No history of second malignancy within the last 5 years. Adequately treated basal carcinoma of skin or carcinoma in situ of cervix is acceptable within this period
- •No serious concomitant disease, no active infections. No autoimmune disease or organ allografts, no clinical suspicion of HIV or Hepatitis B
- •No contra-indications for MRI-scanning: claustrophobia, pacemaker or pacemaker threads, cerebral clips or artificial heartvalves, internal hearing prosthesis No known allergy to shell fish (contains KLH)
- •No pregnant or lactating women
结局指标
主要结局
Immune response
时间窗: during the first 10 years
Migration efficacy
时间窗: during the first 1-2 years
次要结局
- Clinical response(during the first 10 years)