Mature Dendritic Cell Vaccination Against gp100 in Patients With Advanced Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events
研究概览
简要总结
The purpose of this study is to investigate a method of using dendritic cells (a kind of white blood cell) as a vaccine to stimulate your own immune system to react to your melanoma cells.
详细描述
Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production. All patients will be given cyclophosphamide 300mg/m2 IV three days prior to vaccine dose #1 in order to deplete regulatory T cells. All patients will receive mature DC for each dose of vaccine. For each dose all patients will receive autologous dendritic cells pulsed with 2 gp100 melanoma peptides (G209-2M and G280-9V) plus up to an additional 10 unique melanoma tumor-specific peptides. All patients will receive booster doses with mature DC. The DC vaccine will be given intravenously every three weeks for a total of six vaccine doses. Peripheral blood (16 ml) will be taken weekly to monitor the immune response to each peptide by tetramer assay. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Restaging is performed after three and six vaccine doses. Patients with stable disease or better (partial response/complete response) after six doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Unresectable stage III and stage IV M1a/M1b/M1c melanoma including patients with uveal melanoma
- •Age ≥ 18 years
- •Life expectancy ≥ 4 months
- •ECOG performance status 0-2
- •At least 28 days from prior treatment (including adjuvant interferon) except in cases of a BRAF inhibitor (such as vemurafenib); concurrent treatment with a BRAF inhibitor +/- MEK inhibitor is permitted
- •Required initial laboratory values (submitted within 14 days prior to registration):
- •WBC >3,000/mm3
- •Hg ≥ 9.0 gm/dl
- •Platelets >75,000/mm3
- •Serum Bilirubin < 2.0 mg/dl
- •Serum Creatinine < 2.0 mg/dl
- •Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial, and sexually active men must be willing to avoid fathering a new child while receiving therapy.
排除标准
- •Prior treatment with more than one line of cytotoxic chemotherapy; prior treatment with one line of cytotoxic chemotherapy is permitted. Prior treatment with targeted therapy (such as ipilumumab, anti-PD1, and BRAF inhibitor) is permitted.
- •Active untreated CNS metastasis
- •Active infection
- •Prior malignancy (except non-melanoma skin cancer) within 3 years
- •Pregnant or nursing
- •Concurrent treatment with corticosteroids; local (inhaled or topical) steroids are permitted.
- •Inability to provide adequate informed consent
- •Known allergy to eggs
- •Prior history or uveitis or autoimmune inflammatory eye disease.
- •Known positivity for hepatitis BsAg, hepatitis C antibody, or HIV antibody.
研究组 & 干预措施
Dendritic Cell Vaccine (First Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
干预措施: cyclophosphamide (Drug)
Dendritic Cell Vaccine (First Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
干预措施: Mature dendritic cell vaccine (Biological)
Dendritic Cell Vaccine (Second Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
干预措施: cyclophosphamide (Drug)
Dendritic Cell Vaccine (Second Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 3 weeks for a total of 6 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 and dose #6 in order to collect PBMC for immune monitoring. Patients with stable disease or better after 6 doses will be eligible to receive additional vaccinations as maintenance therapy every 2 months until progression.
干预措施: Mature dendritic cell vaccine (Biological)
Dendritic Cell Vaccine (Third Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 6 weeks for a total of 3 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 in order to collect PBMC for immune monitoring.
干预措施: cyclophosphamide (Drug)
Dendritic Cell Vaccine (Third Group)
Blood mononuclear cells will be collected for vaccine production through apheresis. Patients will be given cyclophosphamide 300mg/m2 IV 3 days prior to vaccine dose #1 in order to deplete regulatory T cells. Patients will receive mature DC for each dose of vaccine and will receive autologous dendritic cells. The DC vaccine will be given intravenously every 6 weeks for a total of 3 doses. Peripheral blood will be taken weekly to monitor the immune response. Apheresis is repeated after vaccine dose #3 in order to collect PBMC for immune monitoring.
干预措施: Mature dendritic cell vaccine (Biological)
结局指标
主要结局
Safety and tolerability of the mature dendritic cell vaccine as measured by adverse events
时间窗: 30 days after end of treatment
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
Immunological response based on measuring increased numbers of peptide specific CD8+ T cells as calculated by the tetramer assay.
时间窗: Through completion of treatment
* Starting on Day 0, two tubes will be drawn weekly until Day 64. Thereafter, two tubes will be drawn every 21 days until Day 190. For patients receiving maintenance treatment, blood is drawn every month. * Data are presented as the percentage of CD8+ T cells positive for tetramer binding based on gating variables set using the iMASC reagent kit (Beckman Coulter).
次要结局
- Regulatory T cell depletion after cyclophosphamide administration.(Day -3 (72 hours prior to vaccine dose 1))
- Safety and side effect profile of mDC administered to patients given after a single dose of cyclophosphamide.(Day 0 (prior to vaccine dose 1))
- Time to progression(Through completion of treatment or until progressive disease)
- Clinical response rate using RECIST criteria(After third vaccine, sixth vaccine, and then every 8 weeks)