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

Phase 2

Completed

• Conditions: Melanoma
• Interventions: Drug: low-dose IL-2; Biological: melanoma vaccine

• Registration Number: NCT00928902
• Lead Sponsor: University of Virginia

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 1999-11
• Primary Completion: 2001-04
• Study Completion: 2005-03
• Study First Submitted: 2009-06-24
• Study First Submitted QC: 2009-06-25
• Study First Posted: 2009-06-26
• Status Verified: 2010-10
• Last Update Submitted: 2010-10-20
• Last Update Posted: 2010-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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:

  1. ECOG performance status 0-1, and,
  2. 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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peptides with GM-CSF-in-adjuvant, with upfront IL-2	low-dose 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 1 and ending at week 7.
Peptides with GM-CSF-in-adjuvant, with upfront IL-2	melanoma vaccine	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.
Peptides plus GM-CSF-in-adjuvant, delayed IL-2	low-dose IL-2	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.
Peptides plus GM-CSF-in-adjuvant, delayed IL-2	melanoma vaccine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Changes in disease, analysis of melanoma antigen (gp100, tyrosinase, MART-1) expression on melanoma cells from metastatic sites, Vitiligo.