Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Vaccines

Immunomodulating Agents

Poly ICLC

Monatide (IMS 3015)

Freund's Adjuvant

Adjuvants, Immunologic

Immunologic Factors

Interferons

Vaccines will be administered subcutaneously, intradermally or transdermally in one skin location that is rotated to different sites on an extremity clinically uninvolved with melanoma.

Vaccines will be administered on days 1, 8, 15, 36, 57, and 78.

Cohort 1 will be divided into three sub-groups and will receive:

* Group 1a: MELITAC 12.1 + lipopolysaccharide (LPS)
* Group 1b: MELITAC 12.1 + lipopolysaccharide (LPS) + Montanide adjuvant with vaccination #1
* Group 1c: MELITAC 12.1 + lipopolysaccharide (LPS) adjuvant + Montanide adjuvant with all vaccinations

MELITAC 12.1 + Montanide ISA-51 + lipopolysaccharide (LPS)

Cohort 2 will be divided into three sub-groups and will receive:

* Group 2a: MELITAC 12.1 + polyICLC adjuvant
* Group 2b: MELITAC 12.1 + polyICLC adjuvant + Montanide adjuvant with vaccination #1
* Group 2c: MELITAC 12.1 + polyICLC adjuvant + Montanide adjuvant with all vaccinations

MELITAC 12.1 + Montanide ISA-51 + polyICLC

Craig L Slingluff, MD

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.

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)

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

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

* 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 title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients	NCT01585350	Melanoma	MELITAC 12.1 + ... MELITAC 12.1 + ...	18 Years -	University of Virginia
A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients	NCT01585350	Melanoma	MELITAC 12.1 + ... MELITAC 12.1 + ...	18 Years -	University of Virginia

Spots Global Cancer Trial Database for lipopolysaccharide (lps)