A Pilot Trial of Therapeutic Vaccination With a Modified gp100 Melanoma Peptide (gp100:209-217(210M)), Montanide ISA 51, and KLH With Reconstitution After Chemotherapy to Induce Lymphopenia in Patients With Metastatic Melanoma
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
A Pilot Trial of Therapeutic Vaccination With a Modified gp100 Melanoma Peptide (gp100:209-217(210M)), Montanide ISA 51, and KLH With Reconstitution After Chemotherapy to Induce Lymphopenia in Patients With Metastatic Melanoma
OBJECTIVES:
Primary
- Determine the toxicity and immune effects of vaccination comprising modified gp100
peptide (gp100:209-217[210M]), Montanide ISA-51, and keyhole limpet hemocyanin followed
by peripheral blood mononuclear cell reinfusion after treatment-induced lymphopenia
with fludarabine in patients with unresectable or metastatic melanoma.
- Determine the induction of antigen-specific T-cell responses in patients treated with
this regimen.
- Determine the kinetics and duration of immune response in patients treated with this
regimen.
- Compare the immunologic effects of this regimen in these patients with historical
results.
Secondary
- Compare 2 different dosing schedules of fludarabine, in terms of induction of
lymphopenia and granulocytopenia and on the induction of a specific immune response to
this vaccine, in these patients.
OUTLINE: This is a pilot, randomized study. Patients are randomized to 1 of 2 treatment
arms.
Within 2 weeks before the start of fludarabine, all patients undergo leukapheresis over 4-6
hours for the collection of peripheral blood mononuclear cells (PBMCs).
- Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5.
- Arm II: Patients receive fludarabine as in arm I on days 1, 3, and 5. In both arms,
patients receive autologous PBMCs IV over approximately 30 minutes on day 8 and
vaccination comprising gp100:209-217(210M) peptide, Montanide ISA-51, and keyhole
limpet hemocyanin subcutaneously on days 8, 22, 36, 50, and 64. Patients with stable or
responding disease continue to receive vaccination on day 78 and then every 28-31 days
for up to 1 year.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this
study within 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed malignant melanoma
- Metastatic or unresectable disease
- Measurable disease
- HLA-A2 positive
- Received at least 1 prior immunotherapy and/or chemotherapy regimen for metastatic
disease (first 6 patients only)
- No known brain metastases unless previously treated with radiotherapy and/or surgery
AND is stable for at least 1 month after treatment
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Absolute lymphocyte count ≥ 500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL (transfusions allowed)
- Hematocrit ≥ 24%
- No other active bleeding
Hepatic
- Bilirubin < 2 times upper limit of normal (ULN) (unless due to Gilbert's disease)
- AST and ALT < 3 times ULN
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal
- Creatinine < 2 mg/dL
- No uncontrolled hypercalcemia
Cardiovascular
- No uncontrolled symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
Pulmonary
- No uncontrolled bronchospasm
- No hemoptysis
Immunologic
- Negative serology for all of the following:
- HIV-1 and HIV-2
- HTLV-1 and -2
- Syphilis
- Rheumatoid factor < 43 units/μL
- Anti-nuclear antibody < 11 units/μL
- No history of multiple sclerosis, systemic lupus erythematosus, or myasthenia gravis
- No primary or secondary immunodeficiency
- No active infection
- No allergy to seafood or shellfish that would preclude study participation
Other
- No active gastrointestinal bleeding
- No uncontrolled hyperglycemia
- No other medical or psychiatric condition or social situation that would preclude
study compliance
- No other uncontrolled illness
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3-4 months after
study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior immunization with gp100:209-217(210M) peptide
Chemotherapy
- See Disease Characteristics
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
Endocrine therapy
- More than 2 weeks since prior steroid therapy except replacement steroids or inhaled
steroids
- No concurrent corticosteroids except replacement steroids
- No concurrent dexamethasone
Radiotherapy
- See Disease Characteristics
- More than 2 weeks since prior radiotherapy
Surgery
- See Disease Characteristics
- Recovered from prior surgery
Other
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Toxicity by clinical and laboratory observation at 1 month
Safety Issue:
Yes
Principal Investigator
Walter J. Urba, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Providence Cancer Center, Earle A. Chiles Research Institute
Authority:
United States: Federal Government
Study ID:
CDR0000383908
NCT ID:
NCT00091143
Start Date:
July 2004
Completion Date:
March 2010
Related Keywords:
- Melanoma (Skin)
- recurrent melanoma
- stage III melanoma
- stage IV melanoma
- Melanoma
Name | Location |
|---|---|
| Providence Cancer Center at Providence Portland Medical Center | Portland, Oregon 97213-2967 |
