Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With 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. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Detailed Description
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OBJECTIVES: Compare the immune reactivity in patients with resected stage IIB, IIC, III, or IV melanoma vaccinated with tyrosinase, gp100, and MART-1 peptides emulsified with Montanide ISA-51 with interleukin-12 and either alum adjuvant or sargramostim (GM-CSF). OUTLINE: This is a randomized study. Patients are stratified according to disease stage (cutaneous stage IIB, IIC, III, and IV vs ocular and mucosal stage III and IV). Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive vaccine with tyrosinase:368-376 (370D)/gp100:209-217 (210M)/MART-1:26-27 (27L) peptides emulsified with Montanide ISA-51 (ISA-51), low-dose interleukin-12 (IL-12) subcutaneously (SC), and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53. Arm II: Patients receive peptide vaccine emulsified with ISA-51, high-dose IL-12 SC, and alum adjuvant SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53. Arm III: Patients receive peptide vaccine emulsified with ISA-51 on day 1 and low-dose IL-12 SC and sargramostim (GM-CSF) SC on days 1-5 of weeks 1, 3, 5, 7, 11, 15, 19, 27, and 53. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 60 patients (20 per treatment arm) will be accrued for this study within 3 years.

Official Title
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A Phase II Randomized Trial of a Vaccine Combining Tyrosinase/GP100/MART-1 Peptides Emulsified With Montanide ISA 51 With Interleukin-12 With Alum or GM-CSF for Patients With Resected Stages IIB/C, III and IV Melanoma

Conditions
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Intraocular Melanoma, Melanoma (Skin)

Intervention / Treatment
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* Biological: MART-1 antigen
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant
* Biological: recombinant interleukin-12
* Biological: sargramostim
* Biological: tyrosinase peptide
* Drug: alum adjuvant
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage IIB, IIC, III, or IV cutaneous melanoma OR stage III or IV ocular or mucosal melanoma Resected or rendered disease-free HLA-A2.1-positive by standard cytotoxicity assay Tumor tissue must be available for analysis of gp100 staining and tyrosinase and MART-1 expression by immunohistochemistry Must be positive for at least 1 antigen Failed, ineligible for, or refused prior interferon alfa PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL No bleeding disorder Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 2.5 times normal No coagulation disorder Hepatitis surface antigen B negative Hepatitis C negative Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No major cardiovascular illness Pulmonary: No major respiratory illness Immunologic: No prior uveitis No prior autoimmune inflammatory eye disease No immune hemolytic anemia No other active autoimmune disease Other: HIV negative No major gastrointestinal illness No other malignancy within the past 5 years except squamous cell skin cancer or carcinoma in situ of the cervix curatively treated at least 30 days ago No major systemic infection (e.g., pneumonia or sepsis) No other major medical illness No prior allergic reaction to Montanide ISA-51 or alum adjuvant No requirement for steroid therapy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior tyrosinase:368-376 (370D), gp100:209-217 (210M), or MART-1:26-35 (27L) peptides Chemotherapy: At least 1 month since prior adjuvant chemotherapy for this disease No concurrent adjuvant chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: At least 1 month since prior radiotherapy for this disease No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 1 month since other prior therapy, including adjuvant therapy, for this disease No other concurrent therapy, including adjuvant therapy

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MART-1 antigen|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: recombinant interleukin-12|nan|
|Biological: sargramostim|nan|
|Biological: tyrosinase peptide|nan|
|Drug: alum adjuvant|nan|
|Procedure: adjuvant therapy|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 II melanoma, iris melanoma, ciliary body and choroid melanoma, small size, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, recurrent intraocular melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma