Vaccine Therapy With or Without Sargramostim in Treating Patients With High-Risk or Metastatic Melanoma

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells. PURPOSE: Randomized phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastatic melanoma.

Detailed Description
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OBJECTIVES: Compare the safety of melanoma peptide vaccine with or without sargramostim (GM-CSF) in patients with high-risk or metastatic melanoma. Compare changes in peptide-specific cellular and humoral immunologic profiles in patients treated with these regimens. Compare tumor response in patients treated with these regimens. OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive melanoma peptide vaccine comprising tyrosinase leader injected at 2 separate sites, Melan-A ELA injected at another site, NY-ESO-1a and NY-ESO-1b combined and injected at one site, and MAGE-10.A2 injected at another site, intradermally once weekly on weeks 1-6. Arm II: Patients receive vaccine as in arm I. Patients also receive sargramostim (GM-CSF) subcutaneously daily beginning 2 days before each vaccination and continuing for 5 days. Treatment in both arms continues through week 6 in the absence of disease progression or unacceptable toxicity. Patients are followed at 2 weeks. PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study within 18 months.

Official Title
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A Phase I Study of Peptide Based Vaccine Therapy in Patients With High-Risk or Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: MAGE-10.A2
* Biological: MART-1 antigen
* Biological: NY-ESO-1 peptide vaccine
* Biological: sargramostim
* Biological: tyrosinase peptide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed high-risk stage III or IV melanoma Stage III disease less than 6 months after surgical resection Completed prior interferon alfa therapy OR Progressive disease or major adverse events during prior interferon alfa therapy Stage III disease at least 6 months after surgical resection Declined, failed, or completed prior standard therapy Stage IV disease Declined, failed, or completed prior standard therapy HLA-A2 positive No CNS metastases unless treated and stable PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80-100% Life expectancy: At least 4 months Hematopoietic: Neutrophil count at least 1,500/mm3 Lymphocyte count at least 500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9.0 g/dL (10.0 g/dL if less than 50 kg) No bleeding disorder Hepatic: Bilirubin no greater than 2.0 mg/dL No hepatitis B or C positivity Renal: Creatinine no greater than 1.8 mg/dL Cardiovascular: No New York Heart Association class III or IV heart disease Other: HIV negative No other serious illness No serious infection requiring antibiotics No history of immunodeficiency disease or autoimmune disease No psychiatric or addictive disorder that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior bone marrow or stem cell transplantation At least 4 weeks since prior immunotherapy or biologic therapy No other concurrent immunotherapy or biologic therapy Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) No concurrent chemotherapy Endocrine therapy: No concurrent systemic corticosteroids No concurrent steroids except topical or inhalational steroids Concurrent hormonal therapy allowed Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics At least 4 weeks since prior surgery Other: At least 4 weeks since prior investigational agents Concurrent noncytotoxic anticancer therapy allowed No concurrent immunosuppressive therapy No concurrent antihistamines No concurrent non-steroidal anti-inflammatory drugs except in low doses for prevention of an acute cardiovascular event or pain control

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MAGE-10.A2|nan|
|Biological: MART-1 antigen|nan|
|Biological: NY-ESO-1 peptide vaccine|nan|
|Biological: sargramostim|nan|
|Biological: tyrosinase peptide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III melanoma, stage IV melanoma, recurrent melanoma