Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Metastatic Melanoma

Study Overview
=================
Brief Summary
-----------------
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: Phase II trial to compare the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have metastatic melanoma that has not responded to previous therapy.

Detailed Description
-----------------
OBJECTIVES: Compare the efficacy of gp100:209-217(210M) peptide and MART-1:26-35(27L) peptide administered with or without high-dose interleukin-2 (IL-2) in patients with metastatic melanoma who are HLA-A0201 positive. Determine the efficacy of these peptides in patients who cannot receive IL-2. Compare the efficacy of IL-2 with or without these peptides in patients who need immediate treatment with IL-2. Determine the efficacy of MART-1:26-35(27L) peptide in patients who have received prior gp100 antigen. Compare the immunologic response experienced by patients who have received peptide, with or without IL-2, as measured by changes in T-cell precursors from before to after treatment. Compare the toxic effects of these regimens in these patients. OUTLINE: This is a partially randomized study. Patients are assigned to 1 of 4 treatment groups based on disease status and prior therapy. Group A (eligible to receive interleukin-2 (IL-2) but not in immediate need; no prior immunization with gp100 or MART-1 antigen): Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive gp100 and MART-1 peptides emulsified in Montanide ISA-51 (ISA-51) subcutaneously (SC) on day 1. (Arm I closed as of 10/30/02). Arm II: Patients receive both peptides as in arm I on day 1 and high-dose IL-2 IV over 15 minutes every 8 hours on days 2-5 (for up to 12 doses). (Arm II closed as of 10/30/02). Group B (ineligible to receive IL-2 due to other debilitating disease): Patients receive treatment as in group A, arm I. Group C (need immediate IL-2 therapy due to extensive and rapid progression of disease): Patients receive treatment as in group A, arm II. (Group C closed as of 10/30/02). Group D (prior immunization with gp100 antigen): Patients receive modified MART-1:26-35(27L) peptide emulsified in ISA-51 SC on day 1. Treatment in all groups repeats every 3 weeks for 4 courses. Patients who achieve a minor, mixed, or partial response may receive up to 12 additional courses. Patients who achieve complete response receive 2 additional courses. Patients are followed at 4-6 weeks. PROJECTED ACCRUAL: A total of 103 patients (15-25 for group A, arm I; 19-33 for group A, arm II; and 15 each for groups B, C, and D) will be accrued for this study within 1 year.

Official Title
-----------------
Immunization of Patients With Metastatic Melanoma Using MART-1 and GP100 Peptides Modified to Increase Binding to HLA-0201

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: MART-1 antigen
* Biological: aldesleukin
* Biological: gp100 antigen
* Biological: incomplete Freund's adjuvant


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma that has failed standard therapy Measurable disease HLA-A0201 positive 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 Hepatic: Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL for patients with Gilbert's syndrome) AST/ALT less than 3 times normal Hepatitis B surface antigen negative No coagulation disorder Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No major cardiovascular disease If cardiovascular disease or other debilitating symptoms present, may receive peptide emulsified with Montanide ISA-51 only Pulmonary: No major respiratory disease Other: Not pregnant Fertile patients must use effective contraception HIV negative No active systemic infection No autoimmune disease or immunodeficiency disease No primary or secondary immunodeficiency PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy No prior MART-1 antigen immunization Chemotherapy: At least 3 weeks since prior chemotherapy Endocrine therapy: At least 3 weeks since prior endocrine therapy No concurrent steroid therapy Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: Prior surgery allowed

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MART-1 antigen|nan|
|Biological: aldesleukin|nan|
|Biological: gp100 antigen|nan|
|Biological: incomplete Freund's adjuvant|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

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

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