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Vaccine Therapy and Sargramostim in Treating Patients With Stage IV Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006243
First received: September 11, 2000
Last updated: January 24, 2013
Last verified: January 2013
History of Changes
  Purpose

This randomized pilot clinical trial studies vaccine therapy and sargramostim in treating patients with stage IV malignant melanoma. Vaccines made from melanoma peptides or antigens may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for malignant melanoma


Condition Intervention
Recurrent Melanoma
Stage IV Melanoma
 Biological: tyrosinase peptide
Biological: MART-1:27-35 peptide vaccine
Biological: gp100 antigen
Biological: incomplete Freund's adjuvant
Biological: sargramostim
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Melanoma Vaccines: Differentiation Antigen Peptides (MART-1:27-35, Tyrosinase and Gp-100) as Immune Targets

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Changes in tumor antigen peptide specific immune responses [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    Plots of the percent changes in these factors from their pretreatment levels against time will be constructed.


Secondary Outcome Measures:
  • Number and severity of hematologic and non-hematologic toxicities observed using the Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Proportion of objective responses (complete response [CR] and partial response [PR]) observed [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: October 2000
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (vaccine therapy)
Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.
 Biological: tyrosinase peptide
Given SC
Other Name: TYRP
Biological: MART-1:27-35 peptide vaccine
Given SC
Biological: gp100 antigen
Given SC
Other Name: gp100
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (vaccine therapy and lower-dose sargramostim)
Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and lower-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.
 Biological: tyrosinase peptide
Given SC
Other Name: TYRP
Biological: MART-1:27-35 peptide vaccine
Given SC
Biological: gp100 antigen
Given SC
Other Name: gp100
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (vaccine therapy and higher-dose sargramostim)
Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and higher-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.
 Biological: tyrosinase peptide
Given SC
Other Name: TYRP
Biological: MART-1:27-35 peptide vaccine
Given SC
Biological: gp100 antigen
Given SC
Other Name: gp100
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the immunological effects of immunization protocols utilizing MART-1:27-35 (MART-1:27-35 peptide vaccine), tyrosinase (tyrosinase peptide) or gp-100 (gp100 antigen) peptides suspended in incomplete Freund's adjuvant (IFA) in the presence of two different concentrations of sargramostim (GM-CSF).

II. Define the safety and toxicity profile of an immunization protocol utilizing varying concentrations of MART-1:27-35, tyrosinase and gp-100 peptides suspended in IFA in the presence of two different concentrations of GM-CSF.

III. Collect preliminary data on therapeutic efficacy as it relates to parameters of immune function in patients with stage IV malignant melanoma.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant subcutaneously (SC) on day 1 of weeks 0, 3, 6, 9, 12, and 24.

ARM II: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and lower-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.

ARM III: Patients receive tyrosinase peptide, MART-1:27-35 peptide vaccine, and gp100 antigen admixed in incomplete Freund's adjuvant SC and higher-dose sargramostim SC on day 1 of weeks 0, 3, 6, 9, 12, and 24.

In all arms, treatment may repeat every 3 months for up to 18 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Human leukocyte antigen (HLA)-A2 positive
  • Histologic proof of stage IV malignant melanoma with measurable disease
  • Absolute neutrophil count (ANC) >= 1500
  • Platelets (PLT) >= 100,000
  • Alkaline phosphatase (Alk phos) =< 3 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • Creatinine (Creat) =< 1.5 x ULN
  • Hemoglobin (Hgb) > 9.0
  • Ability to provide informed consent
  • Willingness to return to a Mayo Clinic institution for follow-up
  • Life expectancy >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

  • Uncontrolled or current infection
  • Prior immunization with differentiation antigen peptides
  • Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy

  • Any of the following prior therapies:

    • Chemotherapy =< 4 weeks
    • Mitomycin C/nitrosoureas =< 6 weeks
    • Immunotherapy =<4 weeks
    • Biologic therapy =< 4 weeks
    • Radiation therapy =< 4 weeks
    • Radiation to > 25% of bone marrow
  • Failure to fully recover from effects of prior chemotherapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Seizure disorder

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
  • Other concurrent chemotherapy, immunotherapy, or radiotherapy
  • Active psychiatric disorder requiring medications (anti-psychotics)
  • Known central nervous system metastases or carcinomatous meningitis
  • History of other malignancy in last 5 years with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only (it is impossible to predict the effect of study treatment on other, potentially dormant malignant diseases)
  • Known immune deficiency (patients with known immune deficiencies will likely not be able to mount an immune response to the study vaccine)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006243

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Svetomir Markovic Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006243     History of Changes
Other Study ID Numbers: NCI-2012-02359, MC9973, CDR0000068171
Study First Received: September 11, 2000
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

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
Adjuvants, Immunologic
Freund's Adjuvant
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013