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

January 24, 2013 updated by: National Cancer Institute (NCI)

Melanoma Vaccines: Differentiation Antigen Peptides (MART-1:27-35, Tyrosinase and Gp-100) as Immune Targets

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Biological: tyrosinase peptide
Given SC
Other Names:
  • TYRP
Biological: gp100 antigen
Given SC
Other Names:
  • gp100
Biological: MART-1:27-35 peptide vaccine
Given SC
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.
Other: laboratory biomarker analysis
Correlative studies
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Biological: tyrosinase peptide
Given SC
Other Names:
  • TYRP
Biological: gp100 antigen
Given SC
Other Names:
  • gp100
Biological: MART-1:27-35 peptide vaccine
Given SC
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.
Other: laboratory biomarker analysis
Correlative studies
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Biological: tyrosinase peptide
Given SC
Other Names:
  • TYRP
Biological: gp100 antigen
Given SC
Other Names:
  • gp100
Biological: MART-1:27-35 peptide vaccine
Given SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in tumor antigen peptide specific immune responses
Time Frame: Baseline and 24 weeks
Plots of the percent changes in these factors from their pretreatment levels against time will be constructed.
Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Up to 3 years
Proportion of objective responses (complete response [CR] and partial response [PR]) observed
Time Frame: Up to 3 years
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Svetomir Markovic, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2000

Primary Completion (Actual)

May 1, 2006

Study Registration Dates

First Submitted

September 11, 2000

First Submitted That Met QC Criteria

May 21, 2003

First Posted (Estimate)

May 22, 2003

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02359
  • MC9973
  • CDR0000068171 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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