Phase I/II Trial of a Long Peptide Vaccine (LPV7) Plus TLR Agonists

Inclusion Criteria:

* Histologically or cytologically proven Stage IIB - IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.

  * Patients may have had melanoma from a cutaneous, mucosal or unknown primary site
  * Patients with small radiologic or clinical findings may be eligible
* Patients with treated brain metastases may be eligible if the following are true:

  * Total number of brain metastases ever is less than or equal to 3
  * The brain metastases have been completely removed by surgery or have been treated completely with stereotactic radiotherapy
  * There has been no evident growth of any brain metastases since treatment
  * No treated brain metastases is greater than 2 cm at the time of protocol entry
* Patients must have at least 1 intact axillary and/or inguinal lymph node basin
* ECOG performance status of 0-1
* Lab parameters as follows:

  * HLA-A1, A2, A3, B35, or B51
  * ANC \> 1000/mm3 and Platelets \> 100,000/mm3 and Hemoglobin \> 9 g/dL
  * AST and ALT up to 2.5 x ULN
  * Bilirubin up to 2.5 x ULN
  * Alkaline Phosphatase up to 2.5 x ULN
  * Creatinine up to 1.5 x ULN
  * HGBA1C level ≤ 7.5%

Exclusion Criteria:

* Patients with melanoma from a uveal or ocular primary site
* Patients currently receiving any systemic therapy within 4 weeks of study registration. Gamma knife or stereotactic radiosurgery must not be administered within 1 week prior to study registration. Patients who are currently receiving nitrosoureas within the preceding 6 weeks.
* Patients who have received CTLA-4, PD-1, PD-L1, CD137, or CD27 within the prior 12 months.
* Patients with known or suspected allergy to any component of the vaccine
* HIV positive or active Hepatitis C virus
* Patients receiving any of the following medications within 4 weeks are excluded:

  * Agents with immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids)
  * Allergy desensitization injections
  * Systemic corticosteroids, administered parenterally or orally. Inhaled steroids (e.g. Advair, Flovent, Azmacort) are not permitted. Topical corticosteroids are acceptable including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex)
  * Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
  * Interferon therapy
  * Interleukin-2 or other interleukins
* Other investigational drugs or investigational therapy if currently receiving or have received within 1 month
* Pregnancy or the possibility of becoming pregnant during the study. And women who are breastfeeding.
* Must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. The following are not exclusionary:

  * Presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms
  * Clinical evidence of vitiligo
  * Other forms of depigmenting illness
  * Mild arthritis requiring NSAID medications
* Patients with a medical contradiction or potential problem with complying with the protocol, in the opinion of the investigator
* Patients with Class III or IV heart disease (according to NYHA classification)
* Patients with a body weight \< 110 lbs.