MART-1 Antigen With or Without TLR4 Agonist GLA-SE in Treating Patients With Stage II-IV Melanoma That Has Been Removed by Surgery

This randomized pilot clinical trial studies melanoma antigen recognized by T-cells 1 (MART-1) antigen with or without toll-like receptor 4 (TLR4) agonist glucopyranosyl lipid A-stable oil-in-water emulsion (GLA-SE) in treating patients with stage II-IV melanoma that has been removed by surgery. Vaccines made from MART-1a peptide or antigen may help the body build an effective immune response to kill tumor cells. Giving TLR4 agonist GLA-SE with MART-1 antigen may help increase the immune response to MART-1a antigen.

PRIMARY OBJECTIVES:

I. Evaluate the immune response of each immunization regimen to 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.

TERTIARY OBJECTIVES:

I. Describe the immunological efficacy of the vaccine preparations as measured by the frequency and interferon (IFN) gamma production of peptide-specific cytotoxic T lymphocytes (CTL).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive MART-1 antigen and TLR4 antagonist GLA-SE intramuscularly (IM) on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive MART-1 antigen IM on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, stage II patients are followed up at 10 weeks and then at 6, 12, 18, and 24 months and stage III-IV patients are followed up at 3, 6, 9, 12, 15, 18, 21, and 24 months.

Eligibility Criteria:
Inclusion Criteria:

* Central pathology review submission; Note: this review for MART-1 positivity is mandatory prior to randomization to confirm eligibility
* Human leukocyte antigen (HLA)-A2-positive
* Histologic proof of stage II, III or IV melanoma that has been completely resected or completely treated with ablative therapy (ex: stereotactic body radiosurgery, radiofrequency ablation, cryoablation) 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 any of the vaccine or adjuvant components, including eggs
* Any of the following prior therapies with interval since most recent treatment:

  * Chemotherapy =\< 4 weeks prior to registration
  * Biologic or immunologic therapy =\< 4 weeks prior to registration
  * Radiation therapy =\< 4 weeks prior to registration
* Failure to fully recover from side effects of prior therapy or surgery
* Any of the following:

  * 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
* 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) use of immunosuppressive medications including systemic (inhaled, oral, or intravenous \[IV\]) corticosteroids; Note: use of corticosteroids in doses not exceeding those used for adrenal replacement is acceptable
* History of brain metastases; EXCEPTION: patients with a solitary brain metastasis that has been completely resected, and who have no ongoing central nervous system (CNS) symptoms and an MRI documenting no evidence of CNS disease at least 3 months after resection and within 30 days of registration, are eligible for treatment
* 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 of prior malignancy \> 5 years prior to registration, the patient must not be receiving other cancer treatment