Vaccination of Stage IV Cutaneous Melanoma Patients With Mature, Autologous Monocyte-Derived Dendritic Cells Transfected With Unselected Autologous Amplified Tumor-RNA
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Safety
研究概览
简要总结
RATIONALE: Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IV melanoma.
详细描述
OBJECTIVES:
- Determine the safety and tolerability of vaccine therapy comprising autologous dendritic cells (DC) transfected with autologous polymerase chain reaction-amplified tumor RNA in patients with stage IV cutaneous melanoma.
- Determine whether tumor RNA- or tumor antigen-specific T-cell responses are induced in patients treated with this vaccine.
- Determine whether there are major differences in the immunogenicity of DC transfected at immature stage or at mature stage in patients treated with this vaccine.
- Determine objective tumor response in patients treated with this vaccine.
- Determine time to disease progression and progression-free interval in patients treated with this vaccine.
- Determine overall survival of patients treated with this vaccine.
OUTLINE: This is an open-label, nonrandomized study. Patients are sequentially assigned to receive dendritic cells (DC) transfected at either immature or mature stage.
Approximately 2-3 weeks before leukapheresis, patients undergo surgical excision or biopsy of the tumor to obtain tumor tissue for RNA isolation. RNA is amplified from the tumor sample by polymerase chain reaction (PCR). Patients then undergo leukapheresis to harvest peripheral blood mononuclear cells for the production of DC on day -14 . DC at immature or mature stage are transfected with autologous PCR-amplified tumor RNA to produce the vaccine. Patients receive vaccine intradermally (ID) on days 1, 15, 29, 43, 57, and between days 71-74 in the absence of disease progression or unacceptable toxicity. Patients undergo evaluation between days 71-74. Patients with responding or stable disease or minor disease progression receive booster vaccine ID on days 99, 127, between days 162-164, on day 205, between days 253-255, 351-354, 442-444, 533-535, 624-626, and 715-718 in the absence of disease progression or unacceptable toxicity. Patients also undergo additional leukapheresis between days 71-74, 351-354, and 715-718. Patients with responding or stable disease may continue to undergo leukapheresis and receive booster vaccine ID every 12-24 weeks off study.
After completion of study treatment, patients are followed periodically for up to 10 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed cutaneous melanoma*
- •Stage IV disease (i.e., distant metastasis)
- •Not curable by surgical resection
- •NOTE: *Metastatic melanoma with an unknown primary tumor allowed provided ocular melanoma can be definitely excluded and origin from the skin is likely
- •Unidimensionally or bidimensionally measurable disease by physical examination and/or noninvasive radiological procedures
- •At least 1 measurable metastasis that has not been previously excised or biopsied
- •Failed ≥ 1 standard chemotherapy or chemoimmunotherapy regimen (e.g., dacarbazine or cisplatin monotherapy)
- •At least 1 metastatic lesion surgically accessible* for excision or biopsy to obtain tumor material for RNA isolation** NOTE: *Surgically accessible metastatic lesion not required provided properly processed tumor material or isolated tumor RNA is available from a metastasis excised or biopsied within the past 6 months
- •NOTE: **Major surgery not allowed for the acquisition of metastatic material solely for RNA isolation
- •No active CNS metastases by CT scan or MRI
- •Previously treated CNS metastases (e.g., by excision of a single metastasis, gamma knife radiosurgery, or stereotactic radiotherapy) allowed provided there is no evidence of active CNS metastasis by CT scan or MRI
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 60-100%
- •Life expectancy
- •At least 4 months
- •Hematopoietic
- •WBC > 2,500/mm^3
- •Neutrophil count > 1,000/mm^3
- •Lymphocyte count > 700/mm^3
- •Platelet count > 75,000/mm^3
- •Hemoglobin > 9 g/dL
- •No bleeding disorders
- •Bilirubin < 2.0 mg/dL
- •Hepatitis B surface antigen negative
- •Hepatitis C antibody negative
- •Creatinine < 2.5 mg/dL
- •Cardiovascular
- •No clinically significant heart disease
- •No respiratory disease
- •Immunologic
- •HIV-1 or -2 negative
- •Human T-cell lymphotropic virus type I negative
- •No known hypersensitivity to dimethylsulfoxide
- •No immunodeficiency disease
- •No active systemic infection
- •No active autoimmune disease (except vitiligo), including any of the following:
- •Lupus erythematosus
- •Scleroderma
- •Rheumatoid arthritis (i.e., rheumatoid factor-positive arthritis with current or recent flare)
- •Ankylosing spondylitis
- •Autoimmune thyroiditis or uveitis
- •Autoimmune hemolytic anemia
- •Immune thrombocytopenic purpura
- •Multiple sclerosis
- •Inflammatory bowel disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile female patients must use effective contraception during and for ≥ 4 weeks after completion of study treatment
- 另有 33 项未显示
排除标准
- 未提供
结局指标
主要结局
Safety
Immunogenicity
Objective tumor response
Time to disease progression
Progression-free interval
Overall survival
次要结局
未报告次要终点