A Dose Ranging Trial of Adenovirus CCL-21 Transduced MART-1/gp100 Peptide-Pulsed Dendritic Cells Matured Using Cytokines for Patients With Chemotherapy-Resistant Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Number of Participants with Immune response
研究概览
简要总结
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with metastatic melanoma.
详细描述
In this phase I study, patients will receive intradermal injections of adenovirus-CCL-21 transduced class I peptide-pulsed DC with total volumes for each intradermal injection of no more than 1 ml to be split into four injections of 0.25 ml each in four limbs in node draining areas (proximal arms and thighs), for a total DC dose of 2 X 10^6, 10^7 or 2 X 10^7 cells to be administered intradermally. DC injections in one course of therapy will be given four times at intervals of weekly for two doses (days 1 and 8 +/- 72 hrs.), then every two weeks for two doses (at days 22 +/- 72 hrs. and 36 +/- 72 hours). Cells will be harvested for DC administration and a flow cytometry analysis as well as microbiologic analysis including bacterial/fungal cultures and gram stain will be performed prior to infusion. All injections will be based on number of DC, not number of total cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Metastatic melanoma with measurable disease after attempted curative surgical therapy and who have received at least one prior chemotherapy regimen; adjuvant interferon or isolated limb perfusion is allowed.
- •Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement.
- •Patients must be HLA-A *0201 positive, by a DNA SSOP analysis.
- •Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and ALT/AST of less than 3X institutional upper limit of normal.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients must be able to understand and sign an IRB approved informed consent form.
- •Patients must have white blood count of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more.
- •Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial.
排除标准
- •Undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy
- •Have major systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months
- •Require steroid therapy
- •Patients who are pregnant or lactating
- •Known to be positive for hepatitis BsAg, Hepatitis C or HIV antibody
- •Have a prior history of uveitis or autoimmune inflammatory eye disease
- •Have had another malignancy other than cervical carcinoma-in-situ or basal cell /squamous cancer of the skin, unless they have undergone curative therapy more than 3 years ago and are still free of detectable disease, since the effects of peptide-pulsed DC on other active cancers are unknown
结局指标
主要结局
Number of Participants with Immune response
时间窗: 2 years, 5 months
Assessment of immune responses to the cytokine-cocktail-matured class I peptide-pulsed adenoviral CCL-21 transduced DC cell vaccine. Immune reactivity will be monitored for the appearance of lymphoid-like structures at the vaccine site (as a result of CCL-21 production), in the blood for MART-1 /gp100 specific T cell frequency by tetramer based flow cytometry and ELISPOT analysis of fresh cells, and CTL cytolytic reactivity after in vitro sensitization prior to, four weeks after, and 8 weeks after immunization.
次要结局
- Number of Participants with Adverse Events(2 years, 5 months)