NCT00071981已完成2 期
A Randomized Phase II Trial of Multi-Epitope Vaccination With Melanoma Peptides For Cytotoxic T Cells And Helper T Cells For Patients With Metastatic Melanoma
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 130
- 主要终点
- Cytotoxic T-cell Lymphocytes (CTL) Response Rate
研究概览
简要总结
RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase II trial is studying four different vaccines using melanoma peptides from cytotoxic T cells and helper T cells to see how well they work in treating patients with metastatic melanoma.
详细描述
OBJECTIVES:
- Compare the cytotoxic T-cell response to each of 12 melanoma peptides restricted by Human Leukocyte Antigen (HLA)-A1, -A2, or -A3 in patients with metastatic melanoma vaccinated with or without these 12 melanoma peptides and with or without helper peptides.
- Compare the helper T-cell response to each of 6 melanoma helper peptides restricted by HLA-DR molecules in patients treated with these vaccinations.
- Determine whether the addition of 6 melanoma helper peptides to a vaccine containing multiple class I Major histocompatibility complex (MHC)-restricted peptides augments T-cell responses to the class I restricted peptides in these patients.
- Determine, preliminarily, whether booster vaccination maintains immune response in patients treated with these vaccinations.
- Compare the rates of clinical response and survival in patients treated with these vaccinations.
- Determine, preliminarily, whether cellular immune response correlates with clinical response and survival rates in patients treated with these vaccinations.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to HLA type (HLA-A1 vs HLA-A2 vs HLA-A1 and -A2 vs HLA-A3) and planned sentinel immunized node biopsy (yes vs no). Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (Granulocyte-macrophage colony-stimulating factor, GM-CSF) and Montanide ISA-51 or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
- Arm II: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 1 tetanus helper peptide emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
- Arm III (closed to accrual as of 5/19/08): Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
- Arm IV: Patients receive 2 injections of multi-epitope peptide vaccine comprising 6HP emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
In all arms, patients continue therapy in the absence of unacceptable toxicity or disease progression necessitating other urgent therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically confirmed stage IV melanoma
- •Multiple primary melanomas allowed
- •Metastasis may be from a cutaneous, mucosal, ocular, or unknown primary site
- •Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST criteria)
- •Must have 2 extremities uninvolved with tumor
- •Must have at least 2 intact (undissected) axillary and/or inguinal lymph node basins
- •Prior sentinel node biopsy may not have violated the integrity of a nodal basin
- •This extremity may still be considered for vaccination
- •Human Lymphocyte Antigen (HLA)-A1, -A2, or -A3 positive
- •Prior brain metastases allowed provided all of the following are true:
- •Surgically resected or treated with gamma-knife or stereotactic radiosurgery
- •No disease progression in the brain for the past 3 months
- •More than 30 days since prior steroids for the management of brain metastases
- •Age: 18 and over
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Adequate organ function measured within 4 weeks before randomization:
- •White blood cell (WBC) at least 4,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Lymphocyte count at least 700/mm^3
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) no greater than 2 times upper limit of normal (ULN)
- •Bilirubin no greater than 2 times ULN
- •Alkaline phosphatase no greater than 2 times ULN
- •Lactic dehydrogenase no greater than 2 times ULN
- •Creatinine no greater than 1.8 mg/dL
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other malignancy within the past 5 years except nonmetastatic squamous cell or basal cell skin cancer, ductal or lobular carcinoma in situ of the breast, or carcinoma in situ of the cervix
- •At least 4 weeks since prior sargramostim (GM-CSF), interferon alfa-2b, or interleukin-2
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •More than 30 days since prior systemic corticosteroids, including any of the following:
- •Therapeutic doses of oral steroids (e.g., prednisone or dexamethasone)
- •Steroid inhalers (e.g., Advair)
- •Topical steroids and nasal steroids with low systemic absorption (e.g., fluticasone) or steroids with low systemic absorption (e.g., triamcinolone hexacetonide) injected into a joint space allowed
- •At least 4 weeks since prior local control or palliative radiotherapy and recovered
- •Recovered from prior major surgery
- •Exclusion criteria:
- •More than 3 brain metastases
- •Metastatic lesions greater than 2 cm
- •Concurrent radiotherapy
- •Prior radiotherapy to measurable disease
- •Concurrent surgery
- •Concurrent corticosteroids
- •Concurrent topical or systemic steroids
- •Concurrent chemotherapy
- •Prior vaccination with any of the study peptides
- •Recent (within the past year) or concurrent addiction to alcohol or illicit drugs
- •Pregnant or nursing
- •Known or suspected major allergy to any components of the study vaccine
- •Significant detectable infection
- •Immunosuppression conditions
- 另有 5 项未显示
排除标准
- 未提供
结局指标
主要结局
Cytotoxic T-cell Lymphocytes (CTL) Response Rate
时间窗: Immune response was assessed at pre-registrtion, in weeks 1, 3, 5, 7, 8
Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.
次要结局
- Helper T-cells Response to 6MHP(Immune response was assessed at pre-registration, in weeks 1,3,5,7,8)
- Helper T Cell Response to Tetanus(Immune response was assessed at pre-registration, in weeks 1,3,5,7,8)
- Median Overall Survival (OS)(assessed every 3 month within 2 years and every 6 months betwen 2 and 5 years)
- Objective Response Rate(Tumor response was assessed in weeks 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, and 6 months after last vaccination)
研究者
研究点 (130)
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