Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006385
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 8, 2011
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies such as sargramostim and interferon alfa use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known if vaccine therapy if more effective with or without biological therapy for melanoma.

PURPOSE: Randomized phase II trial to compare the effectiveness of vaccine therapy with or without biological therapy in treating patients who have metastatic melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: MART-1 antigen Biological: gp100 antigen Biological: incomplete Freund's adjuvant Biological: recombinant interferon alfa Biological: sargramostim Biological: tyrosinase peptide Phase 2

Detailed Description:


  • Determine immune response of vaccination with melanoma associated antigens (MART-1:27-35, gp100:209-217 (210M), and tyrosinase:368-376 (370D)) on the number of peptide specific CD8+ T-cell precursors in HLA-A2 positive patients with metastatic melanoma.
  • Determine the influence of sargramostim (GM-CSF) and/or interferon alfa-2b (IFN-A) on the immune responses of these patients and toxicity of this melanoma peptide vaccine.
  • Determine any antitumor and anti-pigmentary response that may result from immunization against MART-1, gp100 and tyrosinase peptides, and determine the relationship between such clinical observations and immune responses against lineage antigens with or without GM-CSF and/or IFN-A.
  • Compare the relapse free survival and overall survival of patients treated with melanoma peptide vaccine alone or in combination with GM-CSF and/or IFN-A.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to 1 of 4 treatment arms.

  • Arm I: Patients receive multiepitope peptide (MEP) vaccine comprising MART-1:27-35, gp100:209-217 (210M), and tyrosinase:368-376 (370D) peptides. Each peptide is separately emulsified in Montanide ISA-51 and administered subcutaneously (SC) (for a total of 2 injections per peptide) on days 1 and 15.
  • Arm II: Patients receive MEP vaccine as in arm I and sargramostim (GM-CSF) subcutaneously (SC) daily on days 1-14.
  • Arm III: Patients receive MEP vaccine as in arm I and interferon alfa-2b SC three times a week.
  • Arm IV: Patients receive MEP vaccine as in arm I, GM-CSF as in arm II, and interferon alfa-2b as in arm III.

Treatment continues every 4 weeks for a maximum of 13 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 92 patients (23 per arm) will be accrued for this study within 13-16 months.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Immunization With an HLA-A2 Multi-Epitope Peptide Vaccine Containing MART-1 (NSC #672643), gp100 (NSC #683472), and Tyrosinase (NSC #699048) Peptides Alone or in Combination With GM-CSF, IFN Alpha-2b, or GM-CSF + IFN Alpha-2b in Patients With Metastatic Melanoma
Study Start Date : September 2000
Actual Primary Completion Date : October 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven stage IV melanoma
  • Measurable disease

    • At least 1 lesion must be a minimum of 1.0 cm in diameter
    • Bone metastases are not considered to be measurable disease
    • No prior radiotherapy to area of measurable disease unless there is clearly progressive disease in this site or measurable disease exists outside the area of prior radiotherapy
  • HLA-A2 positive
  • No brain disease by MRI or CT scan within 4 weeks prior to randomization

    • Prior brain disease allowed if no evidence of active disease by 2 successive MRI evaluations completed at least 3 months apart



  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified


  • WBC at least 4,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Lymphocyte count greater than 700/mm ^3


  • SGOT no greater than 2 times upper limit of normal (ULN)
  • Bilirubin no greater than 2 times ULN
  • Alkaline phosphatase and lactic dehydrogenase no greater than 2 times ULN


  • Creatinine no greater than 1.8 mg/dL


  • No significant detectable infection
  • HIV negative
  • No other malignancy within the past 5 years except:

    • Any carcinoma in situ
    • Lobular carcinoma in situ of the breast
    • Carcinoma in situ of the cervix
    • Atypical melanocytic hyperplasia
    • Melanoma in situ
    • Basal cell or squamous cell skin cancer
  • No autoimmune disorders or conditions of immunosuppression
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy:

  • No prior MART-1:27-35, gp100:209-217 (210M), or tyrosinase:368-376 (370D) peptide
  • Greater than 4 weeks since prior adjuvant immunotherapy, including sargramostim (GM-CSF) or interferon alfa-2b


  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

  • At least 2 weeks since prior and no concurrent systemic corticosteroids, including oral steroids (i.e., prednisone, dexamethasone); continuous use of topical steroid creams or ointments; or any inhalers containing steroids


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy for local control or palliation and recovered


  • Recovered from any prior major surgery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006385

  Show 32 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Study Chair: John M. Kirkwood, MD University of Pittsburgh

Publications of Results:
Kirkwood JM, Lee S, Land S, et al.: E1696: final analysis of the clinical and immunological results of a multicenter ECOG phase II trial of multi-epitope peptide vaccination for stage IV melanoma with MART-1 (27-35), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) (MGT) +/− IFNα2b and GM-CSF. [Abstract] J Clin Oncol 22 (Suppl 14): A-7502, 710s, 2004.
Kirkwood JM, Lee S, Land S, et al.: E1696: phase II trial of multi-epitope peptide vaccination for melanoma with MGT (MART-1 (27-35), gp100 (209-217, 210M) and tyrosinase (368-376, 370D))+/- IFN alfa-2b and GM-CSF--immunological and clinical results. [Abstract] 22: A-2850, 709, 2003. Identifier: NCT00006385     History of Changes
Other Study ID Numbers: CDR0000068263
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: November 8, 2011
Last Verified: December 2002

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Freund's Adjuvant
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic