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
- 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
- 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
- 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
- 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
- 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
- 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.
- Histologically confirmed metastatic melanoma that has failed standard therapy
- Measurable disease
- HLA-A0201 positive
- 16 and over
- ECOG 0-2
- More than 3 months
- WBC at least 3,000/mm^3
- Platelet count at least 90,000/mm^3
- Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL for patients with Gilbert's
- AST/ALT less than 3 times normal
- Hepatitis B surface antigen negative
- No coagulation disorder
- Creatinine no greater than 2.0 mg/dL
- No major cardiovascular disease
- If cardiovascular disease or other debilitating symptoms present, may receive peptide
emulsified with Montanide ISA-51 only
- No major respiratory disease
- 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:
- At least 3 weeks since prior biologic therapy
- No prior MART-1 antigen immunization
- At least 3 weeks since prior chemotherapy
- At least 3 weeks since prior endocrine therapy
- No concurrent steroid therapy
- At least 3 weeks since prior radiotherapy
- Prior surgery allowed