A Randomized Phase II Trial to Determine the Immune Response to a Mutated gp100 Melanoma Peptide (209-2M) Vaccine in HLA-A2 Positive Patients With a >1mm Melanoma on Initial Biopsy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide
研究概览
简要总结
This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick.
II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.
III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.
IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune).
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
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision
- •Patients whose melanoma is > 4.0 mm thick who have positive or negative regional lymph nodes are also eligible
- •After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible
- •Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques
- •Patients must be ambulatory with good performance status (Karnofsky performance status [PS] 80-100)
- •White blood cell (WBC) >= 3500/mm^3
- •Platelets (Plt) >= 100,000/mm^3
- •Hemoglobin >= 9 gm/100 ml
- •Serum creatinine =< 2 mg/dl
- •Total bilirubin =< 2.0 mg/dl
- •Patients must have recovered from any effects of major surgery and be free of significant systemic infection
- •Patients must be negative for human immunodeficiency virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is positive) if they are considered to be at high risk; others do not require serologic testing if there are no symptoms or risk factors for HIV disease
- •Women of childbearing potential must have a negative pregnancy test and should avoid becoming pregnant while on treatment
- •Patients must give written informed consent prior to initiation of therapy; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy
排除标准
- •Patients must not have clinically detectable distant metastases
- •Patients who require or are likely to require systemic corticosteroids for intercurrent illness
- •Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy
- •Patient should be free of any other cancers or deemed at low risk for their recurrence
结局指标
主要结局
T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide
时间窗: Baseline to 6 months
Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods. Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses.
次要结局
未报告次要终点