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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Craig L Slingluff, Jr, University of Virginia
ClinicalTrials.gov Identifier:
NCT00003222
First received: November 1, 1999
Last updated: December 18, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: aldesleukin
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: sargramostim
Biological: tetanus peptide melanoma vaccine
Biological: tyrosinase peptide
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • 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 ]

Enrollment: 40
Study Start Date: April 1998
Primary Completion Date: September 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peptides pulsed on dendritic cells
4 melanoma peptides pulsed on monocyte-derived dendritic cells
Biological: aldesleukin
Systemic subcutaneous delivery of low-dose IL-2.
Other Name: Interleukin-2
Biological: 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.
Biological: aldesleukin
Systemic subcutaneous delivery of low-dose IL-2.
Other Name: Interleukin-2
Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: sargramostim Biological: tetanus peptide melanoma vaccine Biological: tyrosinase peptide

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.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003222

Locations
United States, Virginia
Cancer Center at the University of Virginia
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
National Cancer Institute (NCI)
Investigators
Study Chair: Craig L. Slingluff, MD University of Virginia
  More Information

Publications:
Responsible Party: Craig L Slingluff, Jr, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier: NCT00003222     History of Changes
Other Study ID Numbers: 7621  IRB-HSR 7621  NCI-G98-1389 
Study First Received: November 1, 1999
Results First Received: January 22, 2013
Last Updated: December 18, 2014
Health Authority: United States: Federal Government

Keywords provided by University of Virginia:
stage III melanoma
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Freund's Adjuvant
Aldesleukin
Interleukin-2
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 28, 2016