Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma
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.
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: tetanus peptide melanoma vaccine
Biological: tyrosinase peptide
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- Evaluation of Objective Clinical Response (CR/PR/SD) [ Time Frame: Weeks 0-6,12; Months 6,12 and 24 ] [ Designated as safety issue: No ]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 [ Time Frame: Weeks 0-6,12; Months 6,12 and 24 ] [ Designated as safety issue: No ]
- Measure of Tumor-antigen-specific Immunity in Sentinel Immunized Node (SIN) by Elispot Assay [ Time Frame: Weeks 0-6,12; Months 6,12 and 24 ] [ Designated as safety issue: No ]
|Study Start Date:||April 1998|
|Primary Completion Date:||September 2003 (Final data collection date for primary outcome measure)|
Experimental: Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
Systemic subcutaneous delivery of low-dose IL-2.
Other Name: Interleukin-2Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: tetanus peptide melanoma vaccine Biological: tyrosinase peptide
Experimental: Peptides in GMCSF-in-adjuvant
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Systemic subcutaneous delivery of low-dose IL-2.
Other Name: Interleukin-2Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: sargramostim Biological: tetanus peptide melanoma vaccine Biological: tyrosinase peptide
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003222
|United States, Virginia|
|Cancer Center at the University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|Study Chair:||Craig L. Slingluff, MD||University of Virginia|