Mature Dendritic Cell Vaccination Against Mutated Antigens in Patients With Advanced Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Immune Response Measuring Increased Numbers of Peptide Specific T Cells as Calculated by the Tetramer Assay.
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
This is a single arm open label trial that will assess the safety and tolerability of mature dendritic cell (mDC3/8) vaccine (primer and booster) in subjects with stage III and stage IV melanoma, followed by treatment with pembrolizumab (anti-PD-1 therapy).
Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production approximately 1 week prior to vaccine infusion. Each study subject will receive cyclophosphamide 300mg/m^2 intravenously or by mouth 3 to 4 days prior to the vaccine dose, to deplete regulatory T cells. For each vaccine dose, all subjects will receive autologous dendritic cells pulsed with melanoma tumor-specific peptides. On Day 1, the subject will receive the primer vaccine dose; this will be followed by two booster vaccine doses at 6 weeks apart. Peripheral blood will be taken weekly to monitor the immune response to each peptide by tetramer assay. Re-staging will occur after the 3rd vaccine dose, along with tumor biopsy and second apheresis. Anti PD-1 therapy (standard of care) will commence 7-8 weeks after the subject's last dendritic cell vaccine.
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
- •Histologically confirmed stage III and stage IV M1a/M1b/M1c melanoma. Measurable disease is not required for enrollment eligibility and patients with completely resected disease are permitted.
- •Male or female patients age greater than or equal to 18 years
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- •Required initial laboratory values (performed within 14 days prior to eligibility confirmation by physician-investigator):
- •WBC (white blood cells) >3,000/mm3
- •Hg (hemoglobin) greater than or equal to 9.0 gm/dl
- •Platelets >75,000/mm3
- •Serum Bilirubin < 2.0 mg/dl
- •Serum Creatinine < 2.0 mg/dl
- •Subjects of reproductive potential must agree to use a medically accepted birth control method during the trial and for at least two months following the trial.
- •Provide written informed consent.
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 ipilimumab, anti-PD1, or BRAF + MEK inhibitor combination) is permitted.
- •Active untreated CNS (central nervous system) metastasis
- •Active infection
- •Prior malignancy (except non-melanoma skin cancer) within 3 years
- •Pregnant or nursing (lactating) women
- •Concurrent treatment with high-dose systemic corticosteroids; local (inhaled or topical) steroids are permitted
- •Known allergy to eggs
- •Prior history of uveitis or autoimmune inflammatory eye disease
- •Known positivity for hepatitis B antibody, hepatitis C antibody, or HIV antibody
研究组 & 干预措施
Mature dendritic cell (DC) vaccine
Mature DC 7.5-15 million/peptide given day 1, every six weeks for 2 doses followed by standard of care anti PD-1 therapy
干预措施: Mature dendritic cell (DC) vaccine (Biological)
Mature dendritic cell (DC) vaccine
Mature DC 7.5-15 million/peptide given day 1, every six weeks for 2 doses followed by standard of care anti PD-1 therapy
干预措施: Cyclophosphamide 300mg/m^2 (Drug)
Mature dendritic cell (DC) vaccine
Mature DC 7.5-15 million/peptide given day 1, every six weeks for 2 doses followed by standard of care anti PD-1 therapy
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Immune Response Measuring Increased Numbers of Peptide Specific T Cells as Calculated by the Tetramer Assay.
时间窗: Screening through week 21
Immune response measuring increased numbers of peptide specific T cells as calculated by the tetramer assay. The numbers of Peptide Specific T Cells are reported as the percent of CD8+ T cells that were p/HLA multimer positive for each antigen.
Safety and Tolerability of the Mature Dendritic Cell Vaccine (mDC3/8 Vaccines).
时间窗: End of Study visit (10-28 days after last DC vaccine)
Safety endpoint is type and number of adverse events. Tolerability endpoint is subject's completion or withdrawal from study treatment.
次要结局
- Clinical Response to the mDC3/8 Vaccine(s)(At the End of Study Treatment visit (~10-28 Days after the last DC vaccine))
- Time to Progression Post-mDC3/8 Vaccine Administration(Up to 30 weeks after the first mDC3/8 Vaccine)
- Safety and Side Effect Profile of the Dendritic Cell Vaccine (mDC3/8 Vaccines) Administered to Patients Given After a Single Dose of Cyclophosphamide.(End of Study visit (10-28 days after last DC vaccine))