RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Giving
the vaccine with interleukin-2 or sargramostim may help kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of peptide vaccine with or without
adjuvant interleukin-2 or sargramostim in treating patients who have recurrent or refractory
- Determine whether patients with refractory metastatic melanoma undergo partial or
complete response to peptides specific to their HLA-antigen, either alone or when
combined with 1 of 3 adjuvants.
- Evaluate the immunologic response to the peptide alone or when combined with 1 of 3
adjuvants in these patients.
OUTLINE: Patients are stratified by HLA status (A1 vs A3 vs A24 vs A31).
Patients are assigned to 1 of 4 vaccine groups:
- Group 1 (HLA-A1 positive): Patients receive tyrosinase:240-251.
- Group 2 (HLA-A3 positive): Patients receive gp100:17-25. (closed to accrual 5/17/2000)
- Group 3 (HLA-A24 positive): Patients receive tyrosinase:206-214.
- Group 4 (HLA-A31 positive): Patients receive tyrosinase related protein-1. Each peptide
vaccine is separately emulsified in Montanide ISA-51 and administered subcutaneously
into the thigh. Patients are treated with peptide vaccine alone or combined with 1 of 3
possible adjuvants (interleukin-2 (IL-2) IV, IL-2 delayed IV, or sargramostim (GM-CSF)
SQ) depending on the time of entry into study and response to treatment.
At least 4 to 6 patients are accrued for the peptide alone cohort before beginning accrual
on the other cohorts. Any patient who experiences unacceptable toxicity due to adjuvant
therapy is taken off study. If a second patient develops unacceptable toxicity, that
schedule of peptide administration is discontinued.
Patients exhibiting stable, minor, mixed, or partial response may receive up to 12
Patients are followed for 4-6 weeks.
PROJECTED ACCRUAL: A maximum of 457 patients will be accrued for this study over 3.5 years.
- Histologically proven refractory metastatic melanoma
- Must be HLA-A1, HLA-A3, HLA-A24, or HLA-A31 positive
- Measurable disease
- 16 and over
- ECOG 0-1
- Greater than 3 months
- WBC at least 3,000/mm^3
- Platelet count at least 90,000/mm^3
- No coagulation disorder
- AST or ALT less than 2 times upper limit of normal
- Bilirubin no greater than 1.6 mg/dL
- Creatinine no greater than 2.0 mg/dL
- No major cardiovascular disease
- No major respiratory disease
- Not pregnant
- Fertile patients must use effective contraception
- HIV negative
- Hepatitis B surface antigen negative
- No known allergy to Montanide ISA-51
- No active systemic infection
- No immunodeficiency disease
PRIOR CONCURRENT THERAPY:
- At least 3 weeks since prior biologic therapy
- No concurrent biologic therapy
- At least 3 weeks since prior chemotherapy
- No concurrent chemotherapy
- At least 3 weeks since prior endocrine therapy
- No concurrent steroid therapy or other endocrine therapy
- At least 3 weeks since prior radiotherapy
- No concurrent radiotherapy
- Prior or concurrent surgery for melanoma allowed