Vaccination Plus Ontak in Patients With Metastatic Melanoma

This is an open-label, randomized phase II, single institution study comparing
administration of a 4-peptide melanoma vaccine alone or post-Ontak, in patients with
metastatic melanoma.

Treatment:

1. Cohort A: Vaccine alone. Patients will receive immunization with an emulsion of 4
melanoma peptides (250 mcg each)/GM-CSF/Montanide injected intradermally/subcutaneously
on day 1. A second vaccination will be given 2 weeks later and a third vaccination 2
weeks after that. Patients will be re-evaluated around week 6 and can continue courses
of 3 vaccinations (one every 2 weeks) until disease progression.

2. Cohort B: Ontak plus vaccine. Patients will receive Ontak (18 mcg/kg) intravenously on
day -4 for one dose. On day 0, they will receive the first immunization with an
emulsion of 4 melanoma peptides (250 mcg each)/GM-CSF/Montanide injected
intradermally/subcutaneously. A second vaccination will be given 2 weeks later and a
third vaccination 2 weeks after that. Patients will be re-evaluated around week 6 and
can continue courses of 3 vaccinations (one every 2 weeks) until disease progression.
However, no further Ontak will be given.

Duration: Patients may remain on study until disease progression, unacceptable toxicity,
patient choice to withdraw, or physician decision to discontinue therapy (due to intervening
illness, poor patient compliance, or other situation that would increase patient risk).

Inclusion Criteria:

- Melanoma with evidence of metastatic disease

- Life expectancy of at least 12 weeks.

- Karnofsky performance status index of greater than or equal to 80%.

- Adequate hematopoietic, renal, and hepatic function, defined as:

- Patient must express HLA-A2

- Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and
after therapy, when feasible, to study tumor cell properties and characteristics of
immune cells.

- EKG without evidence of arrhythmia or changes that indicate acute ischemia.

- Pulse oximetry showing oxygen saturation of at least 90% on room air.

Exclusion Criteria:

- Significant cardiovascular disease, or cardiac arrhythmia requiring medical
intervention.

- Pregnant or nursing women.

- Biological therapy in the 4 weeks prior to the start of dosing.

- Patients with intrinsic immunosuppression, including seropositivity for HIV antibody.

- Serious concurrent infection, including active tuberculosis, hepatitis B, or
hepatitis C.

- Concurrent systemic corticosteroids (except physiologic replacement doses)or other
immunosuppressive drugs (eg. cyclosporin A).

- Psychiatric illness that may make compliance to the clinical protocol unmanageable or
may compromise the ability of the patient to give informed consent.

- Active or history of autoimmune disease

- Active gastrointestinal bleeding or uncontrolled peptic ulcer disease.

- Presence of untreated brain metastases.