This study will examine the effectiveness and side effects of an experimental vaccine to
prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients
who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes,
and in patients who have had surgery for metastatic disease (cancer that has spread beyond
the primary site). Melanoma tumors produce proteins called gp100 and MART-1. Vaccination
with specific pieces of these proteins (peptides) may boost the immune system's fight
against the cancer. The vaccine injections are mixed with an oil-based substance called
Montanide ISA-51, which is intended to increase the immune response to the peptide.
Patients 16 years of age and older whose melanoma has been surgically removed and who are
currently free of disease may be eligible for this study. Candidates will be screened with
a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and
other imaging studies will be done if recent results are not available. Some candidates may
require heart tests, such as a cardiac stress test or echocardiogram, or lung function
tests. In addition, all candidates will be tested for HLA tissue type; patients must be
type HLA-A*0201, the type on which this vaccine is based.
Participants will be randomly assigned to receive one of four different vaccines to
determine which peptides offer the best immunity. Each treatment course consists of two
injections of the vaccines every 3 weeks for four times. The injections are given under the
skin of the thigh. After every other treatment course (every 6 months), patients will
undergo a series of x-rays and scans to look for tumor. The immunizations may continue for
up to 12 months as long as the melanoma does not return. The injections are given at the
NIH Clinical Center. Patients are monitored for 1 hour after each injection and have blood
tests and a physical examination to look for treatment side effects.
Patients will be followed with blood tests every 12 weeks to monitor body functions. They
will also undergo leukapheresis-a procedure to collect white blood cells-before starting
treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines
affect the action of the immune system cells. For this procedure, blood is drawn through a
needle in the arm, similar to donating blood. The blood goes through a machine that
separates out the lymphocytes (white blood cells), and the rest of the blood is returned
through a needle in the other arm. Some patients may undergo a biopsy-surgical removal of a
small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue
to examine the effects of the vaccines on the tumor immune cells.
Patients whose disease returns during the first course of vaccine therapy will have surgery
to remove the tumor and will continue to receive the vaccine treatment. Patients whose
tumor returns after completing one course of therapy may receive a substance called
interleukin-2 (IL-2), which can boost immune function against the tumor. IL-2 is given
intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This
regimen is repeated after 10 to 14 days. Those who respond to IL-2 will have a third course
of treatment after 2 months. Patients whose disease recurs after treatment will be taken
off the study and will be referred back to their referring physician or to another study, if
an appropriate one is available.
HLA-A*0201 positive patients at high risk for recurrence of melanoma, or completely resected
metastatic melanoma will receive immunization with peptides representing HLA-restricted T
cell epitopes of the MART-1 or gp100 melanoma antigens emulsified in Montanide ISA-51 or
Montanide(TM) ISA 51 VG. Patients will be randomized to receive one of three different
MART-1 peptides or to receive a combination of a MART-1 peptide plus a gp100 peptide. This
study is designed to evaluate the immunologic effects of the different peptide
- INCLUSION CRITERIA:
HLA-A*0201 patients, age greater than or equal to 16 years, with lesions greater than or
equal to 1.5 mm in thickness, or greater than or equal to 1 positive lymph node, or
ulcerated lesions, or local recurrence, or completely resected metastatic melanoma, within
6 months of surgical resection will be considered. Patients must be clinically disease
free at the time of protocol entry as documented by radiologic studies within 6 weeks of
Serum creatinine of 2.0 mg/dl or less.
Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must
have a total bilirubin less than 3.0 mg/dl.
WBC 3000/mm(3) or greater.
Platelet count 90,000 mm(3) or greater.
Serum AST/ALT less than three times normal.
ECOG performance status of 0 or 1.
Patients of both genders must be willing to practice effective birth control during this
trial because the potential for teratogenic effects are unknown.
Patients may have had prior adjuvant treatment with immunotherapy, including interferon,
or may have had treatment for metastatic disease and are now NED, including chemotherapy
or biotherapy, as long as 3 weeks have elapsed since prior systemic therapy.
Patients will be excluded:
1. who have ocular or mucosal melanoma.
2. who are undergoing or have undergone in the past 3 weeks any systemic therapy except
surgery for their cancer, and must have recovered from any adverse effects of
treatment prior to entry, other than those that do not have clinical implications,
e.g. vitiligo, alopecia.
3. have active systemic infections, autoimmune disease or any known immunodeficiency
4. who require systemic steroid therapy.
5. who are pregnant or breastfeeding.
6. who are known to be positive for hepatitis B(s)AG or HIV antibody.
7. who have any form of active primary or secondary immunodeficiency or who have not
recovered immune competence after chemotherapy or radiation therapy.
8. who have previously been immunized with MART-1.
9. who have known hypersensitivity to any of the agents used in this study.
ELIGIBILITY FOR ADMINISTRATION OF IL-2:
Patients who develop progressive disease while receiving peptide alone must meet the
following criteria to be eligible to receive IL-2:
1. Patients must have measurable metastatic melanoma.
2. Patients may not have active major medical illnesses such as cardiac ischemia,
myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary
3. Patients with recent prolonged history of cigarette smoking or symptoms of
respiratory dysfunction must have a normal pulmonary function test as evidenced by a
FEV(1) greater than 60% predicted.
4. Patients with EKG abnormalities, symptoms of cardiac ischemia or arrhythmias or age
greater than 50 years will have a normal stress cardiac test (stress thallium, stress
MUGA, dobutamine echocardiogram or other stress test).
5. Patients must be willing to sign a durable power of attorney (DPA).
6. Serum creatinine of 2.0 mg/dl or less.
7. Total bilirubin 2.0 mg/dl or less, except in patients with Gilbert's Syndrome who
must have a total bilirubin less than 3.0 mg/dl.
8. WBC 3000/mm(3) or greater.
9. Platelet count 90,000 mm(3) or greater.