A Randomized Phase II Continuation Booster Trial After A Vaccine Combining Tyrosinase/GP100/Mart-1 Peptides Emulsified With Montanide ISA 51 and ISA 51 VG With Or Without GM-CSF For Patients With Resected Stages IIB/C, III And IV Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Immune response
研究概览
简要总结
This randomized phase II trial is studying vaccine therapy and sargramostim to see how well they work compared to vaccine therapy alone in treating patients who have undergone surgery for stage IIB, stage IIC, stage III, or stage IV melanoma. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may make a stronger immune response.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate immune reactivity to a tyrosinase:368-376 (370D) /gp100: 209-217 (210M)/MART-1 26-35 (27L) peptide vaccine with Montanide ISA 51 with or without GM-CSF administered as a booster for five vaccinations over two years.
OUTLINE: This is a randomized, parallel, continuation study. Patients are stratified according to response to prior vaccination (response to 1 peptide vs response to 2 or more peptides). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG subcutaneously (SC) on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
Arm II: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
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
- •Patients who have completed protocol 10M-01-1 or 10M-00-4 are eligible for this study provided that
- •They have received all injections with evidence of an immune response
- •They have not experienced recurrence of the melanoma
- •Not more than twelve months have elapsed since the final injection on either protocol
- •They experienced no grade 3 or 4 toxicity attributed to the prior vaccine regimen
- •Serum creatinine of 2.0 mg/dl or less
- •Total bilirubin of 2.0 mg/dl or less
- •SGOT/SGPT of 2.5 X institutional norm or less
- •Total WBC of 3,000 or more
- •At least 1500 granulocytes
- •Hemoglobin of 9.0 gm/dl or more
- •Platelet count of 100,000 per cu mm. or more
- •ECOG performance status of 0 or 1
- •Patients will be eligible for this trial if they have failed alpha-interferon, if it is felt to be contraindicated due to a pre-existing medical or psychiatric condition or if they have refused treatment with it
- •Ability to read, understand and willingness to sign an IRB-approved informed consent
- •Patients who have had another malignancy but with no evidence of disease for greater than 5 years from accrual to the current trial will be eligible if it is felt they are likely to be cured; patients with squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent can be accrued to this trial 30 days after treatment
排除标准
- •Who have undergone any other systemic therapy for their melanoma, including radiation therapy since completion of 10M-01-1 or 10M-00-4
- •Have major systemic infections like pneumonia or sepsis, coagulation or bleeding disorders, or other major medical illnesses of the gastrointestinal, cardiovascular or respiratory systems
- •Who require systemic, ocular or inhaled corticosteroids
- •Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase, MART-1 or gp100 is felt to present a risk to the fetus or a breast feeding infant; effective birth control for men and women is required during and for four months after the study is finished
- •Who are known to be positive for hepatitis BsAg, hepatitis C antibody or HIV antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of melanoma peptides might be detrimental to HIV positive patients, patients positive for the above viruses will not be treated on this trial
- •Who have had a known allergic reaction to GM-CSF, Montanide ISA 51 (IFA) or any of the peptides included in this protocol
- •Who have a prior history of uveitis or autoimmune inflammatory eye disease, immune hemolytic anemia or other active autoimmune disease
研究组 & 干预措施
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: gp100 antigen (Biological)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: tyrosinase peptide (Biological)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: gp100 antigen (Biological)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: MART-1 antigen (Biological)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: incomplete Freund's adjuvant (Biological)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: Montanide ISA 51 VG (Drug)
Arm I (vaccine therapy)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
干预措施: laboratory biomarker analysis (Other)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: tyrosinase peptide (Biological)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: MART-1 antigen (Biological)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: incomplete Freund's adjuvant (Biological)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: Montanide ISA 51 VG (Drug)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: sargramostim (Biological)
Arm II (vaccine therapy, sargramostim)
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Immune response
时间窗: Week 106
Summarized using means and confidence intervals (after transformation to render the data compatible with the assumptions of the normal distribution).
次要结局
- Disease-free survival(Up to 2 years)
- Overall survival(Up to 2 years)