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

NCT01585350 | Completed Phase 1 DMC

• 1 other identifier: 15781
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma

Keywords

melanoma; peptide vaccine; polyICLC; lipopolysaccharide (LPS); immunotherapy

Outcome Measures

Primary Outcomes (2)

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

  over 6 months

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

  over 6 months

Secondary Outcomes (8)

• Toll-like receptor signaling in the replicate immunization site

  over 6 months

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

  over 6 months

• 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.

  over 6 months

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

  over 6 months

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

  over 6 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

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.

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

Cohort 2

EXPERIMENTAL

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.

Biological: MELITAC 12.1 + Montanide ISA-51 + polyICLC

Interventions

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

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

Cohort 1

MELITAC 12.1 + Montanide ISA-51 + polyICLC BIOLOGICAL

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

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven melanoma that meets one of the following two criteria:
• Stage IIB-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
• Stage III or IV melanoma with disease. Patients may be eligible if there are definite or equivocal findings of persistent or metastatic disease as long as those findings do not meet RECIST criteria for measurable disease.
• Patients with brain metastases may be eligible if all of the following are true:
• The total number of brain metastases ever is less than or equal to 3.
• The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy. Stereotactic radiotherapy, such as gamma knife, can be used up to 1 week prior to study entry.
• There has been no evident growth of any brain metastasis since treatment.
• No treated brain metastasis is greater than 2 cm in diameter at the time of protocol entry.
• Patients must have at least two intact axillary and/or inguinal lymph node basins.
• All patients must have:
• ECOG performance status of 0 or 1.
• Ability and willingness to give informed consent.
• Laboratory parameters as follows:
• HLA-A1, A2, A3, -A11, or -A31
• ANC \> 1000/mm3

You may not qualify if:

• Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other experimental therapy, or who have received this therapy within the preceding 4 weeks. Gamma knife or stereotactic radiosurgery may be administered within the prior 4 weeks, but must not be administered less than one week prior to study enrollment. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks.
• Patients with clinically detectable melanoma deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation.
• Patients with known or suspected allergies to any component of the vaccine.
• Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded:
• Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids
• Allergy desensitization injections.
• Systemic corticosteroids, administered parenterally or orally. Inhaled steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex®).
• Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
• Interferon therapy.
• Interleukin-2 or other interleukins.
• Toll-like receptor agonists, including imiquimod or resiquimod.
• Patients who have recurred or progressed either after or during administration of a melanoma vaccine may be eligible to enroll 12 weeks following their last vaccination.
• Patients may have been vaccinated previously with peptide vaccines (except that they may not have been vaccinated with peptides included in MELITAC 12.1 or MELITAC 12.6)
• Patients may have been vaccinated with protein, DNA, or cell-based vaccines that include the proteins from which these peptides are derived.
• Other investigational drugs or investigational therapy if the patient is currently taking those drugs/therapy, or if they have received the drugs/therapy within 1 month.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• University of Virginia: collaborator
• National Cancer Institute (NCI): collaborator
• Oncovir, Inc.: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• Pollack KE, Meneveau MO, Melssen MM, Lynch KT, Koeppel AF, Young SJ, Turner S, Kumar P, Sol-Church K, Mauldin IS, Slingluff CL Jr. Incomplete Freund's adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment. J Immunother Cancer. 2020 Apr;8(1):e000544. doi: 10.1136/jitc-2020-000544.

  PMID: 32350119 DERIVED

• Melssen MM, Petroni GR, Chianese-Bullock KA, Wages NA, Grosh WW, Varhegyi N, Smolkin ME, Smith KT, Galeassi NV, Deacon DH, Gaughan EM, Slingluff CL Jr. A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund's adjuvant in melanoma patients. J Immunother Cancer. 2019 Jun 27;7(1):163. doi: 10.1186/s40425-019-0625-x.

  PMID: 31248461 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

montanide ISA 51; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Officials

• Craig L Slingluff, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: April 25, 2012
• Study Start: October 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: October 1, 2014
• Last Updated: August 12, 2016

Record last verified: 2016-08

Locations

US (1)