Phase II Trial for the Evaluation of the Efficacy of Vaccination With Synthetic Melanoma Peptides Either Pulsed on Dendritic Cells, or Administered With GM-CSF-in-Adjuvant, Plus Administration of Sustemic IL-2, in Patients With Advanced 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
- Evaluation of Objective Clinical Response (CR/PR/SD)
研究概览
简要总结
RATIONALE: Vaccines made from melanoma cells may make the body build an immune response to and kill tumor cells. Colony-stimulating factors such as GM-CSF may increase the number of immune cells found in the bone marrow or peripheral blood. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Combining vaccine therapy with GM-CSF and interleukin-2 may be kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of vaccines made from melanoma cells with or without GM-CSF followed by interleukin-2 in treating patients with stage III or stage IV melanoma.
详细描述
OBJECTIVES: I. Compare the effectiveness of vaccination with synthetic melanoma peptides pulsed on autologous dendritic cells versus vaccination with synthetic melanoma peptides plus sargramostim (GM-CSF) in decreasing tumor burden in patients with high risk melanoma (pulsed autologous dendritic cell arm closed 1/8/2001). II. Determine whether these regimens result in increased tumor specific immune responses as measured in vitro and in vivo. III. Determine whether these regimens stimulate T-cell responses in these patients.
OUTLINE: This is an open label study. Patients are included in treatment arm II only (arm I closed 1/8/2001): Arm I: Patients undergo leukapheresis to collect dendritic cells. Patients receive a mixture of synthetic melanoma peptides (gp100 antigen, tyrosinase, and tetanus peptides) pulsed on autologous dendritic cells IV and subcutaneously (SC). Arm II: Patients receive a mixture of synthetic melanoma peptides (gp100 antigen, tyrosinase, and tetanus peptides) and sargramostim (GM-CSF) emulsified in Montanide ISA-51 SC and intradermally. Patients receive vaccination during weeks 0, 1, 2, 4, 5, and 6 for a total of 6 doses and interleukin-2 SC daily on days 7-49. Patients receive 3 additional vaccinations at different sites not involved with the tumor concurrently with the first 3 vaccinations. Patients are evaluated at 8 weeks, 12 weeks, 6 months, 12 months, and 24 months.
PROJECTED ACCRUAL: A total of 27-54 patients will be accrued for this study within 2 years.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage III or IV melanoma gp100 positive tumor cells and/or tyrosinase positive tumor cells HLA type A1, A2, or A3 Measurable disease May have up to 3 brain metastases if all are less than 2 cm in diameter and are asymptomatic, and there is no mass effect or they have been treated successfully by surgical excision or by gamma knife radiation therapy
- •PATIENT CHARACTERISTICS: Age: 18 to 79 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class II, III, or IV heart disease Other: No known or suspected allergy to any component of the vaccine No medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 months since prior growth factors At least 3 months since prior agents with putative immunomodulating activity (except nonsteroidal antiinflammatory agents) At least 1 year since other prior melanoma vaccinations Chemotherapy: At least 3 months since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 3 months since prior corticosteroids No concurrent corticosteroids Radiotherapy: At least 3 months since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 3 months since other prior investigational drugs or therapy At least 3 months since prior allergy desensitization injections At least 14 days since completion of acute treatment for a serious infection No concurrent allergy desensitization injections
排除标准
- 未提供
研究组 & 干预措施
Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
干预措施: tetanus peptide melanoma vaccine (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: tetanus peptide melanoma vaccine (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: gp100 antigen (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: tyrosinase peptide (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: sargramostim (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: incomplete Freund's adjuvant (Biological)
Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
干预措施: aldesleukin (Biological)
Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
干预措施: tyrosinase peptide (Biological)
Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
干预措施: incomplete Freund's adjuvant (Biological)
Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
干预措施: gp100 antigen (Biological)
Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
干预措施: aldesleukin (Biological)
结局指标
主要结局
Evaluation of Objective Clinical Response (CR/PR/SD)
时间窗: Weeks 0-6,12; Months 6,12 and 24
The primary end point for this trial was clinical response. This was assessed by measurement of assessable metastatic deposits by CT, MRI, or direct measure of cutaneous deposits. Baseline tumor measurements used for assessment of clinical response were those obtained most immediately before the first vaccine administration and within 6 weeks of protocol entry. Measurements were made and reviewed by a multidisciplinary team. The original protocol defined tumor response on the basis of changes in cross-sectional area calculated as the product of two perpendicular measures. However, since the initiation of this study, the Response Evaluation Criteria in Solid Tumors Group (RECIST) system was employed as the current standard for clinical trials, in which response is based on changes in maximum cross-sectional dimensions. Computed tomography scans of clinical responders were reviewed again by a senior faculty radiologist not otherwise involved in the study.
Measure of Tumor-antigen-specific Immunity in Peripheral Blood Mononuclear Cells (PBMC) by Elispot Assay
时间窗: Weeks 0-6,12; Months 6,12 and 24
Measure of Tumor-antigen-specific Immunity in Sentinel Immunized Node (SIN) by Elispot Assay
时间窗: Weeks 0-6,12; Months 6,12 and 24
次要结局
未报告次要终点
研究者
Craig L Slingluff, Jr
Principal Investigator
University of Virginia