A Phase III Multi-Institutional Randomized Study of Immunization With the gp100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 185
- 试验地点
- 19
- 主要终点
- Best Response Rate (Partial Response [PR] + Complete Response [CR])
研究概览
简要总结
This randomized phase III trial studies aldesleukin with vaccine therapy to see how well it works compared to aldesleukin alone in treating patients with melanoma that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Aldesleukin may stimulate a person's white blood cells to kill melanoma cells. Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether combining aldesleukin with vaccine therapy is more effective than aldesleukin alone in treating melanoma.
详细描述
PRIMARY OBJECTIVES:
I. To identify whether the addition of the peptide vaccine to high dose interleukin (IL)-2 (aldesleukin) can result in a clinical response rate which may be superior to that found in similar patients treated with high dose IL-2 alone.
SECONDARY OBJECTIVES:
I. To evaluate the toxicity profile of patients treated on this trial, according to the regimen received.
II. To compare the disease free/progression free survival of patients treated on both arms of the study.
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
- Single (Investigator)
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
- •Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered
- •Serum creatinine of 1.6 mg/dl or less
- •Total bilirubin 1.6 mg/dl or less
- •White blood cell (WBC) 3000/mm^3 or greater
- •Platelet count 90,000 mm^3 or greater
- •Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients of both genders must be willing to practice effective birth control during this trial
- •Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study
- •Tissue type human leukocyte antigen (HLA) A0201
排除标准
- •Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal
- •Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site
- •Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders
- •Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated
- •Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks
- •Patients who are pregnant
- •Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen [HBsAg] or anti hepatitis C virus [HCV]) or human immunodeficiency virus (HIV) (HIV antibody)
- •Patients who have any form of primary or secondary immunodeficiency
- •Patients who have received previous high dose IL-2 (> 600,000 IU/kg)
- •Patients who have received previous gp100 vaccines
- •Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
- •Patients who have abnormal pulmonary function tests (forced expiratory volume in one second [FEV1] < 65% or forced vital capacity [FVC] < 65% of predicted)
- •Patients who have brain metastasis or history of brain metastasis
- •No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
研究组 & 干预措施
Arm I (aldesleukin)
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Aldesleukin (Biological)
Arm I (aldesleukin)
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Quality-of-Life Assessment (Other)
Arm I (aldesleukin)
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Questionnaire Administration (Other)
Arm I (aldesleukin)
Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Aldesleukin (Biological)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: gp100 Antigen (Biological)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Montanide ISA 51 VG (Drug)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Quality-of-Life Assessment (Other)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Questionnaire Administration (Other)
Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Best Response Rate (Partial Response [PR] + Complete Response [CR])
时间窗: Up to 12 years
A complete response (CR) was defined as the disappearance of all clinical evidence of disease for at least 4 weeks. A partial response (PR) was defined as a 50% or greater decrease in the sum of the products of perpendicular diameters of all measurable lesions for at least one month. No new lesions could appear, and none could increase 25% or more.
次要结局
- Change in T-cell Precursors(Baseline to up to 12 years)
- Progression Free Survival(From the date of randomization until documentation of progression or last follow up, assessed up to 12 years)
- Change in Quality of Life (QOL) Score Assessed by the FACT-G (Functional Assessment of Cancer Therapy- General), FACT-F (Functional Assessment of Cancer Therapy- Fatigue), SF-36 (Short Form 36) and SDS (Symptom Distress Scale)(Baseline to up to 8 weeks)