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.
- Determine the clinical responses in patients with HLA-A0201-positive refractory
metastatic melanoma treated with tyrosinase-related protein-2:180-188 peptide vaccine
- 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.
- 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
- 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
- No coagulation disorders
- 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
- Creatinine no greater than 2.0 mg/dL
- No major medical illness of the cardiovascular system
- No cardiac ischemia*
- No myocardial infarction*
- No cardiac arrhythmias* NOTE: * For interleukin-2 (IL-2) administration
- No major medical illness of the respiratory system
- No obstructive or restrictive pulmonary disease (for IL-2 administration)
- HIV negative
- No primary or secondary immunodeficiency
- No known immunodeficiency disease
- No autoimmune disease
- No active systemic infections
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT 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
- At least 3 weeks since prior chemotherapy for melanoma and recovered
- No concurrent chemotherapy for melanoma
- At least 3 weeks since prior endocrine therapy for melanoma
- No concurrent systemic steroid therapy
- No concurrent endocrine therapy for melanoma
- See Disease Characteristics
- At least 3 weeks since prior radiotherapy for melanoma and recovered
- No concurrent radiotherapy for melanoma
- See Disease Characteristics
- No other concurrent therapy for melanoma