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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Recurrent Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Biological: tyrosinase peptide
* Biological: MART-1:27-35 peptide vaccine
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: sargramostim
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (vaccine therapy)<br>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<br>* Given SC<br>* Other names: TYRP;Biological: MART-1:27-35 peptide vaccine<br>* Given SC<br>Biological: gp100 antigen<br>* Given SC<br>* Other names: gp100;Biological: incomplete Freund's adjuvant<br>* Given SC<br>* Other names: Montanide ISA 51;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (vaccine therapy and lower-dose sargramostim)<br>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<br>* Given SC<br>* Other names: TYRP;Biological: MART-1:27-35 peptide vaccine<br>* Given SC<br>Biological: gp100 antigen<br>* Given SC<br>* Other names: gp100;Biological: incomplete Freund's adjuvant<br>* Given SC<br>* Other names: Montanide ISA 51;Biological: sargramostim<br>* Given SC<br>* Other names: Prokine;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm III (vaccine therapy and higher-dose sargramostim)<br>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<br>* Given SC<br>* Other names: TYRP;Biological: MART-1:27-35 peptide vaccine<br>* Given SC<br>Biological: gp100 antigen<br>* Given SC<br>* Other names: gp100;Biological: incomplete Freund's adjuvant<br>* Given SC<br>* Other names: Montanide ISA 51;Biological: sargramostim<br>* Given SC<br>* Other names: Prokine;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in tumor antigen peptide specific immune responses | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of hematologic and non-hematologic toxicities observed using the Common Toxicity Criteria (CTC) version 2.0 |  | Up to 3 years | 
| Proportion of objective responses (complete response [CR] and partial response [PR]) observed |  | Up to 3 years |