An Extended Dosing, Two-phase Study of MDX-010 as Monotherapy or in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 VG in the Treatment of Subjects With Resected Stage III or Stage IV Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Immune-related Adverse Events (irAEs)
研究概览
简要总结
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma.
PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.
详细描述
OBJECTIVES:
Primary
- Achieve at least a 40% autoimmune breakthrough event rate, as defined by the induction of grade 1, grade 2, or acceptable grade 3 drug-related autoimmune adverse events, in patients with resected stage III or IV melanoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51.
Secondary
- Determine the incidence of drug-related autoimmune adverse events of any grade in patients treated with this regimen.
- Determine the time to disease relapse in patients treated with this regimen.
- Determine the immunologic response in patients treated with this regimen.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed melanoma
- •Stage III (≥ 3 positive lymph nodes) or stage IV disease
- •Mucosal or ocular melanoma allowed
- •Completely resected within the past 6 months
- •Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa
- •Positive staining of tumor tissue for at least one of the following:
- •Antibody HMB-45 for gp100
- •Antibody HMB-45 for tyrosinase
- •Antibody HMB-45 for MART-1
- •HLA-A*0201 positive by DNA allele-specific polymerase chain reaction assay
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •At least 6 months
- •Hematopoietic
- •WBC ≥ 2,500/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hematocrit ≥ 30%
- •Hemoglobin ≥ 10 g/dL
- •AST ≤ 3 times upper limit of normal (ULN)*
- •Bilirubin ≤ ULN* (< 3.0 mg/dL for patients with Gilbert's syndrome)
- •No significant hepatic disease that would preclude study participation
- •Hepatitis B surface antigen negative
- •Hepatitis C antibody negative NOTE: * Unless attributable to disease
- •Creatinine ≤ 2.0 mg/dL
- •No significant renal disease that would preclude study participation
- •Cardiovascular
- •No significant cardiac disease that would preclude study participation
- •No significant pulmonary disease that would preclude study participation
- •Immunologic
- •No history of any of the following:
- •Inflammatory bowel disease or any other autoimmune bowel disease
- •Systemic lupus erythematosus
- •Rheumatoid arthritis
- •Autoimmune ocular disease
- •No systemic hypersensitivity to Montanide ISA-51 or any vaccine component
- •No active infection requiring therapy
- •HIV negative
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
- •No significant gastrointestinal disease that would preclude study participation
- •No significant psychiatric disease that would preclude study participation
- •No other medical condition that would preclude study participation
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for at least 4 months after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- 另有 18 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm 1
干预措施: Tyrosinase/gp100/MART-1 Peptides (Biological)
Arm 1
干预措施: ipilimumab (Biological)
结局指标
主要结局
Percentage of Participants With Immune-related Adverse Events (irAEs)
时间窗: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
Percentage of participants who experienced an irAE during the course of the study defined by the induction of Grade 1, Grade 2, or acceptable Grade 3 drug-related irAEs. For the purposes of this trial, acceptable drug-related irAEs are skin-related immune-mediated adverse events \< or = Grade 3 (potentially reversible inflammation \< Grade 4 that can be attributable to a local antitumor reaction that could potentially be a therapeutic response will also be considered an acceptable irAE). Note: The confidence interval was calculated using the Clopper Pearson method
Time to Disease Relapse
时间窗: up to 3 years
To determine the time (months) from first dose to disease relapse. Time to disease relapse is defined from the start of treatment to the first occurrence of any new lesion (reported by the investigator on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma) or death. Participants who neither relapse nor died will be censored on the date of their last tumor evaluation. Median estimated using Kaplan-Meier method; A two-sided 95% CI for median in each treatment group was computed via the log-log transformation method.
次要结局
- Number of Participants With Drug-related irAEs of Any Grade(Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase))
- Number of Participants Experiencing Hematology-related Lab Abnormalities(Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase))
- Immunologic Response to the Dose Regimen(up to 3 years)
- Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities(Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase))
- Time to Disease Relapse(up to 3 years)