A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients — MEL58  

Melanoma Clinical Trial

Official title: A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients, With Evaluation of the Injection Site Microenvironment

Status Completed

Clinical Trial Summary

The purpose of this study is to learn the effects an experimental vaccine (MELITAC 12.1) combined with other substances called lipopolysaccharide (LPS; endotoxin), polyICLC, and Montanide ISA-51. The LPS, polyICLC, and Montanide ISA-51 are included with the vaccine to test whether they have an effect on the MELITAC 12.1 vaccine. The study will also look at whether the experimental vaccine and these drugs cause any changes to the immune system.

Clinical Trial Description

Goals:

1. To determine the safety of intradermal and subcutaneous injection of lipopolysaccharide (LPS) as a vaccine adjuvant with a multipeptide vaccine.

2. To obtain preliminary data on whether administration of a multipeptide vaccine plus each of 2 TLR agonists is immunogenic with or without Incomplete Freund's Adjuvant (IFA)

3. To obtain preliminary data on whether addition of either of 2 toll-like receptor (TLR) agonists improve the persistence of circulating CD8+ T cell responses to vaccination with a multipeptide vaccine.

4. To determine the local and systemic toxicities of administration of a multipeptide vaccine with each of 2 TLR agonists, and with or without incomplete Freund's adjuvant.

5. To determine the cytokine and chemokine profile of the vaccine-site microenvironment week 1 after injection of a multipeptide vaccine and each of 2 TLR agonists, with or without IFA.

6. To obtain preliminary data on T cell activation status and apoptosis in the vaccine site microenvironment (VSME) as a function of vaccine adjuvant.

7. To assess whether circulating CD8 T cells induced by vaccination express different homing receptor profiles (CLA, CXCR3, α4β1 integrin, α4β7 integrin).

8. To evaluate dendritic cell activation and function in sentinel immunized nodes draining the site of vaccination, for production of IDO, arginase, IL10, IL12.

9. To characterize MyD88 expression in dendritic cells infiltrating vaccination sites.

10. To identify regulatory processes in the vaccination site.

Design: This is an open-label, randomized, pilot study of cellular and molecular events at the cutaneous site of immunization with a multipeptide vaccine. This and related peptide vaccines have been associated with immunologic efficacy in a majority of participants and have been associated with clinical tumor regressions in some participants. The maximum number of participants accrued will be 51.

Endpoints:

Primary:

• Safety, with measures of adverse events, locally and systemically

• CD8+ and CD4+ peptide-reactive T cell responses among lymphocytes in the peripheral blood and in sentinel immunized nodes (SIN)

Secondary:

• Toll-like receptor signaling in the replicate immunization site

• CCR and integrin expression on vaccine induced T cells in the peripheral blood and at the replicate immunization site

• Th1, Th2, and Th17 profiles of T cells in the vaccination site and SIN as measured by cytokine expression (IFNγ, IL-2, TNFα, IL-4, IL-5, IL-10, IL-17, IL-23), and nuclear expression of transcription factors (T-bet, GATA3, RORγt) by immunohistochemistry.

• Chemokines CXCL9, 10, and 11; CCL19, CCL21, CXCL12, CXCL13 in the vaccine site microenvironment.

• Markers of activation, regulation, and apoptosis on CD4 and CD8 T cells in the vaccine site and SIN: CD69, Ki67, FoxP3, and TUNEL staining.

• Homing receptors expressed by antigen-reactive (tetramer-positive) T cells induced by vaccination, in the circulation and SIN.

• MyD88 expression in the VSME and SIN

• Regulatory processes in the immunization site and SIN

• Regulatory T cells (CD4+CD25hi FoxP3+)

• Myeloid suppressor cells

• Indole-amine dioxygenase

• PD-1, B7-H1

• IL-10 and IL-12 expression by dendritic cells (DC) ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

• NCT number: NCT01585350
• Study type: Interventional
• Source: University of Virginia
• Status: Completed
• Phase: Phase 1
• Start date: October 2012
• Completion date: October 2014