This randomized pilot phase II trial studies how well vaccine therapy works in treating
human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with
melanoma. Vaccines made from peptides may help the body build an effective immune response
to kill tumor cells.
I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M]
peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20
peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients
who present with a primary melanoma > 1 mm thick.
II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and
the unmodified parental glycoprotein 100 (gp100) peptide.
III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1
restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.
IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide
tetramers is an effective method for monitoring the immune response of patients undergoing
peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT),
limiting dilution analysis (LDA) and measurement of intracellular cytokine production
V. To determine whether there is a difference between the induction of primary
peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7
VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a
total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide
vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6
months. Treatment continues in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide
vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment
continues in the absence of disease progression or unacceptable toxicity.
In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the
second vaccination. Patients with positive lymph nodes undergo complete lymph node
dissection and resume vaccinations.
After completion of study treatment, patients are followed up every 3 months for 1 year,
every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.
- Patients must have histologically confirmed primary melanoma of Breslow thickness
1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however,
those who have already undergone a wide local excision are also eligible; patients
may be enrolled up to three months after their wide local excision
- Patients whose melanoma is > 4.0 mm thick who have positive or negative regional
lymph nodes are also eligible
- After accrual to the original 26 patient goal, all patients must be enrolled prior to
sentinel lymph node dissection; patients with previous lymph node dissection will not
- Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic
techniques, flow cytometry, or molecular techniques
- Patients must be ambulatory with good performance status (Karnofsky performance
status [PS] 80-100)
- White blood cell (WBC) >= 3500/mm^3
- Platelets (Plt) >= 100,000/mm^3
- Hemoglobin >= 9 gm/100 ml
- Serum creatinine =< 2 mg/dl
- Total bilirubin =< 2.0 mg/dl
- Patients must have recovered from any effects of major surgery and be free of
significant systemic infection
- Patients must be negative for human immunodeficiency virus (HIV) antibody by
enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is
positive) if they are considered to be at high risk; others do not require serologic
testing if there are no symptoms or risk factors for HIV disease
- Women of childbearing potential must have a negative pregnancy test and should avoid
becoming pregnant while on treatment
- Patients must give written informed consent prior to initiation of therapy; patients
with a history of major psychiatric illness must be judged able to fully understand
the investigational nature of the study and the risks associated with the therapy
- Patients must not have clinically detectable distant metastases
- Patients who require or are likely to require systemic corticosteroids for
- Patients with any significant medical disease other than the malignancy (e.g. chronic
obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions)
which in the opinion of the investigator would significantly increase the risk of
- Patient should be free of any other cancers or deemed at low risk for their