Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma

Phase 2

Completed

Conditions: Melanoma (Skin)

Interventions: Biological: aldesleukin
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: tetanus peptide melanoma vaccine
Biological: sargramostim
Biological: tyrosinase peptide

Registration Number: NCT00003222

Lead Sponsor: University of Virginia

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peptides pulsed on dendritic cells	tetanus peptide melanoma vaccine	4 melanoma peptides pulsed on monocyte-derived dendritic cells
Peptides pulsed on dendritic cells	tyrosinase peptide	4 melanoma peptides pulsed on monocyte-derived dendritic cells
Peptides in GMCSF-in-adjuvant	incomplete Freund's adjuvant	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Peptides pulsed on dendritic cells	aldesleukin	4 melanoma peptides pulsed on monocyte-derived dendritic cells
Peptides pulsed on dendritic cells	gp100 antigen	4 melanoma peptides pulsed on monocyte-derived dendritic cells
Peptides in GMCSF-in-adjuvant	sargramostim	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Peptides pulsed on dendritic cells	incomplete Freund's adjuvant	4 melanoma peptides pulsed on monocyte-derived dendritic cells
Peptides in GMCSF-in-adjuvant	aldesleukin	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Peptides in GMCSF-in-adjuvant	gp100 antigen	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Peptides in GMCSF-in-adjuvant	tetanus peptide melanoma vaccine	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Peptides in GMCSF-in-adjuvant	tyrosinase peptide	4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.

Primary Outcome Measures

Name	Time	Method
Evaluation of Objective Clinical Response (CR/PR/SD)	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	Weeks 0-6,12; Months 6,12 and 24
Measure of Tumor-antigen-specific Immunity in Sentinel Immunized Node (SIN) by Elispot Assay	Weeks 0-6,12; Months 6,12 and 24

Secondary Outcome Measures