Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma That Has Not Responded to Previous Treatment

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining vaccine therapy with interleukin-2 may be an effective treatment for metastatic melanoma. PURPOSE: Randomized phase II trial to compare the effectiveness of vaccine therapy plus interleukin-2 to that of vaccine therapy alone in treating patients who have metastatic melanoma that has not responded to previous treatment.

Detailed Description
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OBJECTIVES: Determine the clinical responses in patients with HLA-A0201-positive refractory metastatic melanoma treated with tyrosinase-related protein-2:180-188 peptide vaccine alone. Determine the clinical response rate of patients who have an immediate need to receive interleukin-2 (IL-2) in addition to this vaccine. Compare the immunologic response, in terms of changes in T-cell precursors before and after treatment, in patients treated with this vaccine with or without IL-2. Compare the toxicity profile of these regimens in these patients. OUTLINE: This is a randomized, open-label study. Patients who need immediate interleukin-2 (IL-2) receive tyrosinase-related protein-2 (TRP-2):180-188 peptide vaccine emulsified with Montanide ISA-51 on day 1 and high-dose IL-2 IV over 15 minutes once every 8 hours on days 2-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients who do not need immediate IL-2 are randomized to 1 of 2 treatment arms. Arm I: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 subcutaneously (SC) on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive TRP-2:180-188 peptide vaccine emulsified with Montanide ISA-51 SC once weekly on weeks 1-4. Treatment repeats every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients who have a complete response (CR) receive 1 additional course after achieving CR. Patients who have progressive disease while receiving vaccine alone may cross over to receive peptide vaccine with IL-2 for at least 2 courses. Patients are followed at 3 weeks. PROJECTED ACCRUAL: A maximum of 83 patients (19-33 who need immediate interleukin-2 (IL-2); 15-25 per treatment arm who do not need immediate IL-2) will be accrued for this study within 1 year.

Official Title
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Immunization of HLA-0201 Positive Patients With Metastatic Melanoma Using a Peptide From Tyrosinase-related Protein 2 (TRP-2)

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: aldesleukin
* Biological: incomplete Freund's adjuvant
* Biological: recombinant tyrosinase-related protein-2


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of metastatic melanoma Refractory to standard therapy No resectable locoregional disease HLA-A0201 positive Measurable disease Previously resected brain metastases, brain metastases stable after prior radiosurgery, or brain metastases less than 1 cm and without edema allowed PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-2 Life expectancy: More than 3 months Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 90,000/mm^3 No coagulation disorders Hepatic: Bilirubin no greater than 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome) AST/ALT less than 3 times normal Hepatitis B surface antigen negative Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No major medical illness of the cardiovascular system No cardiac ischemia* No myocardial infarction* No cardiac arrhythmias* NOTE: * For interleukin-2 (IL-2) administration Pulmonary: No major medical illness of the respiratory system No obstructive or restrictive pulmonary disease (for IL-2 administration) Immunologic: HIV negative No primary or secondary immunodeficiency No known immunodeficiency disease No autoimmune disease No active systemic infections Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy for melanoma No prior immunization to tyrosinase-related protein-2 antigen No other concurrent biologic therapy for melanoma Chemotherapy: At least 3 weeks since prior chemotherapy for melanoma and recovered No concurrent chemotherapy for melanoma Endocrine therapy: At least 3 weeks since prior endocrine therapy for melanoma No concurrent systemic steroid therapy No concurrent endocrine therapy for melanoma Radiotherapy: See Disease Characteristics At least 3 weeks since prior radiotherapy for melanoma and recovered No concurrent radiotherapy for melanoma Surgery: See Disease Characteristics Other: No other concurrent therapy for melanoma

Ages Eligible for Study
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Minimum Age: 16 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: aldesleukin|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: recombinant tyrosinase-related protein-2|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 IV melanoma, recurrent melanoma