Vaccine Therapy and Resiquimod in Treating Patients With Stage II-IV Melanoma That Has Been Removed By Surgery

PRIMARY OBJECTIVES:

I. Evaluate the immune response of each immunization regimen and determine an optimal regimen
in terms of immune response to recommend for phase II testing.

SECONDARY OBJECTIVES:

I. Evaluate the adverse events profile of each immunization regimen. II. Evaluate
disease-free survival.

TERTIARY OBJECTIVES:

I. Describe the immunological efficacy of the vaccine preparations with Gag267-274
(Gag:267-274 peptide vaccine) and resiquimod, as measured by the frequency and interferon
(IFN)gamma production of peptide-specific cytotoxic T lymphocytes (CTL).

II. Examine immune responses to the tumor antigen analog MART-1a (MART-1 antigen) versus the
xenoantigen Gag267-274.

OUTLINE: Patients are assigned to 1 of 3 treatment groups.

ARM I: Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in
Montanide ISA 51 VG subcutaneously (SC) on day 1.

ARM II: Patients receive MART-1 antigen emulsified in Montanide ISA 51 VG SC followed by
resiquimod applied topically on day 1.

ARM III: Patients receive MART-1 antigen and Gag:267-274 peptide vaccine emulsified in
Montanide ISA 51 VG SC followed by resiquimod applied topically on day 1.

In all arms, treatment repeats every 21 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12 and 24 months.

Inclusion Criteria:

- Central pathology review submission; this review for MART-1 positivity is mandatory
prior to registration to confirm eligibility

- Human leukocyte antigen (HLA)-A2-positive

- Histologic proof of stage II, III or IV melanoma that has been completely resected
with no current evidence of disease, as demonstrated by imaging within 2 months (stage
III or stage IV; must be computed tomography [CT], magnetic resonance imaging [MRI],
or positron emission tomography [PET]/CT) or 6 months (stage II; may be chest x-ray,
CT, MRI, or PET/CT)

- Absolute neutrophil count (ANC) >= 1500 mL

- Hemoglobin (Hgb) > 10 g/dL

- Platelets (PLT) >= 50,000 mL

- Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)

- Alkaline phosphatase =< 3 x ULN

- Ability to provide informed consent

- Willingness to return to Mayo Clinic Rochester for follow-up

- Life expectancy >= 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- For women of childbearing potential, a negative serum pregnancy test =< 7 days prior
to registration

- Willingness to provide mandatory blood samples for correlative research

Exclusion Criteria:

- Uncontrolled or current infection

- Known standard therapy for the patient's disease that is potentially curative or
proven capable of extending life expectancy

- Known allergy to vaccine or adjuvant components

- Any of the following prior therapies with interval since most recent treatment:

- Chemotherapy =< 4 weeks prior to registration

- Biologic therapy or immunotherapy =< 4 weeks prior to registration

- Radiation therapy =< 4 weeks prior to registration

- Failure to fully recover from side effects of prior chemotherapy or surgery

- Any of the following, as this regimen may be harmful to a developing fetus or nursing
child:

- Pregnant women

- Nursing women

- Women of childbearing potential or their sexual partners who are unwilling to
employ adequate contraception (condoms, diaphragm, birth control pills,
injections, intrauterine device [IUD], surgical sterilization, subcutaneous
implants, or abstinence, etc.)

- Known immune deficiency, including human immunodeficiency virus (HIV) infection, as
patients with known immune deficiencies will likely not be able to mount an immune
response to the study vaccine; in addition, study patients should be naive to the
HIV-derived Gag267-274 antigen

- History of systemic autoimmune disease, as patients with ongoing autoimmunity may be
at an increased risk of autoimmune toxicity from the study vaccine

- Current or recent (=< 4 weeks prior to registration) use of immunosuppressive
medications including systemic corticosteroids; (use of corticosteroids in doses not
exceeding those used for adrenal replacement is acceptable)

- History of brain metastases (even if completely resected)

- Other active malignancy =< 5 years prior to registration; EXCEPTIONS: Non-melanotic
skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior
malignancy, they must not be receiving other treatment for their cancer