Randomized Comparison of Three Schedules of Peptide Immunization in Patients With Stage II or III, or Completely Resected Metastatic Melanoma
16 Years
N/A
Both
Melanoma (Skin)
Trial Information
Randomized Comparison of Three Schedules of Peptide Immunization in Patients With Stage II or III, or Completely Resected Metastatic Melanoma
OBJECTIVES:
- Compare the immunologic activity of three different schedules of peptide immunization
with gp100:209-217 (210M) or gp100:17-25 antigen and tyrosinase:368-376 (370D),
tyrosinase:240-251 (244S), tyrosinase:206-214 (closed to accrual 11/05/01), or
tyrosinase-related protein-1 (ORF3):1-9 peptide (closed to accrual 11/05/01) emulsified
in Montanide ISA-51 in patients with melanoma at high risk for recurrence.
- Compare the response rate to treatment with interleukin-2 (IL-2) after being immunized
with this regimen with the usual response rate to IL-2 in this patient population.
- Determine whether an exploratory cohort of HLA-A2-positive patients demonstrate
immunologic activity to immunization with 2 peptides emulsified together.
OUTLINE: This is a randomized study. Patients are stratified according to HLA type (A0201 vs
A1 vs A3 vs A24 vs A31). (HLA-A24 and HLA-A31 closed to accrual 11/05/01). Patients are
randomized to 1 of 3 treatment arms and are given an assigned vaccine, which is emulsified
in Montanide ISA-51.
- HLA typing:
- HLA-A2: gp100:209-217 (210M) and tyrosinase:368-376 (370D)
- HLA-A1: tyrosinase:240-251 (244S)
- HLA-A3: gp100:17-25
- HLA-A24: tyrosinase:206-214 (closed to accrual 11/05/01)
- HLA-A31: tyrosinase-related protein-1 (ORF3):1-9 (closed to accrual 11/05/01)
- Arm I: Patients receive assigned vaccine subcutaneously (SC) weekly for 10 weeks
followed by 3 weeks of no treatment.
- Arm II: Patients receive assigned vaccine SC on days 1, 22, 43, and 64.
- Arm III: Patients receive assigned vaccine SC on days 1-4, 22-25, 43-46, and 64-67.
Treatment in all arms repeats every 13 weeks for 4 courses in the absence of disease
progression or unacceptable toxicity.
After the completion of the randomized arms of HLA-A2 patients, additional HLA-A2 patients
receive immunization with gp100:209-217 (210M) and tyrosinase:368-376 (370D) emulsified in
Montanide ISA-51 SC once every 3 weeks for 4 courses.
Patients with progressive disease may receive interleukin-2 IV over 15 minutes every 8 hours
for up to 4 days. Treatment repeats every 10-14 days for at least 4 courses in the absence
of disease progression or unacceptable toxicity. Patients with stable disease or mixed or
partial response to treatment may receive additional courses every 2 months.
Patients are followed at 6 months.
PROJECTED ACCRUAL: A total of 324 patients (19-33 per arm for the HLA-A0201 stratum, 13-16
per arm for the other 4 strata, and 33 per the additional HLA-A2 cohort) will be accrued for
this study within 2 years. (HLA-A24 and HLA-A31 closed to accrual 11/05/01).
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of melanoma, including one of the following characteristics:
- Lesions at least 1.5 mm in thickness
- At least 1 positive lymph node
- Ulcerated lesion
- Local recurrence
- Metastatic lesions completely resected within the past 6 months
- Clinically disease free within the past 6 weeks
- HLA-A1, A3, A24, A31, or 0201 positive (HLA-A24 and HLA-A31 closed to accrual
11/05/01)
- No ocular or mucosal melanoma
PATIENT CHARACTERISTICS:
Age:
- 16 and over
Performance status:
- ECOG 0-1
Life expectancy:
- Not specified
Hematopoietic:
- WBC at least 3,000/mm^3
- Platelet count at least 90,000/mm^3
Hepatic:
- Bilirubin no greater than 1.6 mg/dL (3.0 mg/dL in Gilbert's syndrome)
- AST and ALT less than 3 times normal
- Hepatitis B surface antigen negative
Renal:
- Creatinine no greater than 2.0 mg/dL
Cardiovascular:
- For interleukin-2 (IL-2) therapy:
- No cardiac ischemia, myocardial infarction, or cardiac arrhythmias
- Stress cardiac test required if abnormal EKG, symptoms of cardiac ischemia or
arrhythmia, or older than 50 years
Pulmonary:
- For IL-2 therapy:
- No obstructive or restrictive pulmonary disease
- FEV_1 greater than 60% predicted if prolonged history of cigarette smoking or
symptoms of respiratory dysfunction
Other:
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No active systemic infections, autoimmune disease, or active primary or secondary
immunodeficiency
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 3 weeks since prior systemic biologic therapy for melanoma
- No prior gp100 antigen or tyrosinase or TRP-1 peptide
- No other concurrent systemic biologic therapy for melanoma
Chemotherapy:
- At least 3 weeks since prior systemic chemotherapy and recovered
- No concurrent systemic chemotherapy for melanoma
Endocrine therapy:
- At least 3 weeks since prior systemic endocrine therapy for melanoma
- No concurrent systemic steroid therapy
Radiotherapy:
- At least 3 weeks since prior systemic radiotherapy and recovered
- No concurrent systemic radiotherapy for melanoma
Surgery:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Steven A. Rosenberg, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Federal Government
Study ID:
CDR0000068299
NCT ID:
NCT00020358
Start Date:
September 2000
Completion Date:
October 2007
Related Keywords:
- Melanoma (Skin)
- stage I melanoma
- stage II melanoma
- stage III melanoma
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
