Vaccination With Autologous Dendritic Cells Pulsed With Tumor Antigens for Treatment of Patients With Malignant Melanoma. Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Primary aim of the study is to evaluate tolerability and safety of the treatment
研究概览
简要总结
The aim of the study is to show if vaccination with autologous dendritic cells pulsed with peptides or tumor lysate in combination with adjuvant cytokines and Cyclophosphamide can induce a measurable immune response in patients with metastatic malignant melanoma, and to evaluate the clinical effect (objective response rate) of the vaccination regime.
详细描述
Eligible patients receive vaccination with tumor antigen pulsed autologous monocyte-derived mature dendritic cells with a fixed interval. The dendritic cells are generated from leukapheresis products and frozen after antigen loading.
HLA A2 positive patients are treated with PADRE and oncopeptide pulsed DC; p53, survivin and telomerase peptides. HLA A2 negative patients are treated with KLH and tumorlysate pulsed DC; autologous or allogeneic. Each patient is given 6 immunizations with at least 5x106 peptide/lysate pulsed autologous DC. Vaccination 1-4 is given weekly and 4-6 at 2-week intervals. Those patients who exhibit stable disease, partial response or complete response after 6 injections will be given 4 more vaccinations at 2-week interval. The vaccine is applied by intradermal injection near the inguinal region.
IL-2 2 MIU s.c. day 2-6, Cyclophosphamide (Sendoxan®, Baxter A/S) 50 mg twice a day bi-weekly and 200 mg Celecoxib (Celebra®, Pfizer) daily are used. Scans and re-staging tests are performed at scheduled intervals throughout the study.
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
- 否
入选标准
- •Histologically proven progressive metastatic or locally advanced melanoma
- •No standard treatment indicated
- •Age: > 18
- •WHO-Performance Status 0-1
- •At least tone measurable tumor lesions according to the RECIST criteria.
- •Life expectancy more than 3 months
- •Acceptable CBC and blood chemistry results
- •Written informed consent
排除标准
- •Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin).
- •Patients with metastatic disease in the central nervous system (CNS).
- •Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure.
- •Patients with acute or chronic infection including HIV, hepatitis and tuberculosis.
- •Patients who are pregnant.
- •Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial.
- •Patients who receive corticosteroids or other immunosuppressive agents.
- •Baseline serum LDH greater than 2.5 times the upper limit of normal.
- •Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.
结局指标
主要结局
Primary aim of the study is to evaluate tolerability and safety of the treatment
时间窗: weekly the first four weeks thereafter biweekly
次要结局
- Secondary aims: evaluation of treatment induced immune response and clinical response.(after 8 and 16 weeks)