Trial for the Evaluation of the Effect of Systemic Low-dose Interleukin-2 (IL-2) on the Immunogenicity of a Vaccine Comprising Synthetic Melanoma Peptides Administered With Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)-In-Adjuvant, in Patients With High Risk Melanoma

Study Overview
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Brief Summary
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This clinical pilot study will test the hypothesis that systemic low-dose IL-2 therapy significantly enhances the immunologic efficacy of a vaccine comprising melanoma peptides plus GM-CSF-in-adjuvant.

Official Title
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Pilot Phase II Trial for the Evaluation of the Effect of Systemic Low-dose IL-2 on the Immunogenicity of a Vaccine Comprising Synthetic Melanoma Peptides Administered With GM-CSF-in-Adjuvant, in Patients With High Risk Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: low-dose IL-2
* Biological: melanoma vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been diagnosed, by cytologic or histologic examination, with AJCC stage IIB, stage III or resected stage IV melanoma. Patients with up to 2 brain metastases less than or equal to 2 cm that have been surgically removed or treated successfully with the gamma-knife are eligible. Surgical resections must have been performed within 6 months prior to entry. All patients must have: ECOG performance status 0-1, and, Ability and willingness to give informed consent. Laboratory parameters as follows: HLA-A1, A2 or A3 (+) gp100 (+) and/or tyrosinase (+) tumor cells ANC > 1000/mm3, and Platelets > 100,000 and Hgb > 9 Hepatic: AST and ALT up to 2.5 x upper limits of normal (ULN), Bilirubin up to 2.5 x ULN, Alkaline phosphatase up to 2.5 x ULN Renal: Creatinine up to 1.5 x ULN Serology: HIV negative, Hepatitis C negative Exclusion criteria: Patients who are currently receiving cytotoxic Chemotherapy or radiation or who have received that therapy within the preceding 4 weeks. Patients with known or suspected allergies to any component of the vaccine. Patients receiving the following medications at study entry or within the preceding 30 days are excluded: Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents) Allergy desensitization injections Corticosteroids, administered parenterally or orally - topical corticosteroids are acceptable Any growth factors, Interleukin 2, Interferon alfa. Prior melanoma vaccinations will not be an exclusion criteria if given more than 8 weeks previously, but will be recorded, and data analysis will take this into account. Other investigational drugs or investigational therapy also will not necessarily be an exclusion criteria, but will similarly be recorded and taken into account during data analysis. Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the first vaccine dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. This is consistent with existing standards of practice for vaccine and chemotherapy protocols. Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator. Patients classified according to the New York Heart Association classification system as having Class II, III or IV heart disease. Patients with active connective tissue disease requiring medication, or other severe autoimmune disease. Patients who are actively hyperthyroid. Patients with uncontrolled diabetes.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Peptides with GM-CSF-in-adjuvant, with upfront IL-2<br>Each of the peptides plus tetanus toxoid peptide, plus GM-CSF in adjuvant, administered subcutaneously and intradermally. Systemic low-dose IL-2 will be administered daily for 6 weeks, beginning at week 1 and ending at week 7. | Drug: low-dose IL-2<br>* low-dose IL-2, administered daily for 6 weeks, to begin either at week 1 (group 1) or week 4 (group 2)<br>Biological: melanoma vaccine<br>* six melanoma vaccines given over a 6-week period<br>|
| Active Comparator: Peptides plus GM-CSF-in-adjuvant, delayed IL-2<br>Peptides plus GMCSF-in-adjuvant, with delayed IL-2. Each of the peptides plus tetanus toxoid peptide, plus GM-CSF in adjuvant, administered subcutaneously and intradermally. Systemic low-dose IL-2 will be administered daily for 6 weeks, beginning at week 4 and ending at week 10. | Drug: low-dose IL-2<br>* low-dose IL-2, administered daily for 6 weeks, to begin either at week 1 (group 1) or week 4 (group 2)<br>Biological: melanoma vaccine<br>* six melanoma vaccines given over a 6-week period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of systemic low-dose IL-2 on the immunogenicity of a vaccine comprising synthetic melanoma peptides plus GM-CSF-in-adjuvant. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in disease, analysis of melanoma antigen (gp100, tyrosinase, MART-1) expression on melanoma cells from metastatic sites, Vitiligo. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, vaccine, peptides, adjuvant, immunogenicity, stage IIB, stage III or resected stage IV