RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.
Combining an immune adjuvant with a vaccine may cause a stronger immune response and kill
more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of immune adjuvant
when given together with vaccine therapy and to see how well they work in treating patients
with stage IIB, stage IIC, stage III, or stage IV melanoma.
- Determine the maximum tolerated dose and recommended dose of sargramostim (GM-CSF)
plasmid DNA adjuvant with a multi-epitope peptide vaccine comprising tyrosinase peptide
and gp100 antigen in patients with stage IIB, IIC, III, or IV melanoma who are
- Determine the safety of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the dose-limiting toxic effects of this regimen in these patients.
- Determine the immunogenicity of this regimen in these patients.
- Determine any anti-tumor response in patients treated with this regimen.
OUTLINE: This is a phase I, pilot, dose-escalation study of sargramostim (GM-CSF) plasmid
DNA adjuvant followed by a phase II, pilot study.
- Phase I: Patients receive GM-CSF plasmid DNA adjuvant subcutaneously (SC) on day 1 and
a vaccine comprising tyrosinase peptide and gp100 antigen SC on day 5. Treatment
repeats every 28 days for a total of 3 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of GM-CSF plasmid DNA adjuvant until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive vaccination as in phase I at the MTD. After completion of
study, patients are followed up for 1 year.
PROJECTED ACCRUAL: A total of 3-27 patients (3-18 for phase I and 9 for phase II) will be
accrued for this study within 2-14 months.
- Histologically confirmed malignant melanoma
- Stage IIB, IIC, III, or IV disease
- Patients with resectable disease must have undergone surgical resection before study
- Patients free of disease after surgical resection are eligible up to 6 months
- HLA-A0201 positive
- No detectable brain metastases by brain MRI or CT scan
- Any age if weight > 25 kg (55 lb)
- Karnofsky 80-100%
- Not specified
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
- No active bleeding
- Lactic dehydrogenase ≤ 2 times upper limit of normal (ULN)
- Albumin ≥ 3.5 mg/dL
- AST ≤ 2 times ULN
- Creatinine ≤ 2 mg/dL
- No prior creatinine > 2 mg/dL
- Must weigh ≥ 25 kg
- No medical condition that would preclude study participation (e.g., active autoimmune
disease or immunodeficiency)
- No pre-existing retinal or choroidal eye disease
- No inflammation of the eyes
- No serious underlying medical conditions
- No active infection requiring antimicrobial drugs
- Not pregnant or nursing
- At least 3 months post-partum
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 3 months
after study participation
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior immunotherapy
- No prior vaccines containing tyrosinase peptide or gp100 antigen or peptides derived
from tyrosinase peptide or gp100 antigen
- No other concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- No concurrent chemotherapy
- More than 6 weeks since prior systemic corticosteroids
- Inhaled or nasal steroids allowed
- More than 4 weeks since prior radiotherapy
- No concurrent radiotherapy
- See Disease Characteristics
- Recovered from prior surgery
- Recovered from all prior therapy
- No concurrent medication that would preclude study participation