Phase I/II Trial of a Long Peptide Vaccine (LPV7) Plus TLR Agonists (MEL60)

Open Label, Randomized, Phase I/II Study of a Long Peptide Vaccine Plus TLR Agonists for Resected Stage IIb-IV Melanoma. (MEL60)

The purpose of this study is to learn what effects (good and bad) an experimental vaccine (LPV7) plus tetanus peptide and other substances called polyICLC, resiquimod, and Montanide ISA-51 have on you and your melanoma. We will also look at whether the experimental vaccine and these drugs cause any changes in your immune system.

Study Overview

• Status: Completed
• Conditions: Melanoma; Metastatic Melanoma; Mucosal Melanoma
• Intervention / Treatment: Biological: Peptide Vaccine (LPV7) + Tetanus peptide; Other: IFA; Other: PolyICLC; Other: Resiquimod

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MDAnderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically proven Stage IIB - IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.

  • Patients may have had melanoma from a cutaneous, mucosal or unknown primary site
  • Patients with small radiologic or clinical findings may be eligible

• Patients with treated brain metastases may be eligible if the following are true:

  • 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 with stereotactic radiotherapy
  • There has been no evident growth of any brain metastases since treatment
  • No treated brain metastases is greater than 2 cm at the time of protocol entry
• Patients must have at least 1 intact axillary and/or inguinal lymph node basin
• ECOG performance status of 0-1

• Lab parameters as follows:

  • HLA-A1, A2, A3, B35, or B51
  • ANC > 1000/mm3 and Platelets > 100,000/mm3 and Hemoglobin > 9 g/dL
  • AST and ALT up to 2.5 x ULN
  • Bilirubin up to 2.5 x ULN
  • Alkaline Phosphatase up to 2.5 x ULN
  • Creatinine up to 1.5 x ULN
  • HGBA1C level ≤ 7.5%

Exclusion Criteria:

• Patients with melanoma from a uveal or ocular primary site
• Patients currently receiving any systemic therapy within 4 weeks of study registration. Gamma knife or stereotactic radiosurgery must not be administered within 1 week prior to study registration. Patients who are currently receiving nitrosoureas within the preceding 6 weeks.
• Patients who have received CTLA-4, PD-1, PD-L1, CD137, or CD27 within the prior 12 months.
• Patients with known or suspected allergy to any component of the vaccine
• HIV positive or active Hepatitis C virus

• Patients receiving any of the following medications within 4 weeks are excluded:

  • Agents with 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
• Other investigational drugs or investigational therapy if currently receiving or have received within 1 month
• Pregnancy or the possibility of becoming pregnant during the study. And women who are breastfeeding.

• Must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. The following are not exclusionary:

  • Presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms
  • Clinical evidence of vitiligo
  • Other forms of depigmenting illness
  • Mild arthritis requiring NSAID medications
• Patients with a medical contradiction or potential problem with complying with the protocol, in the opinion of the investigator
• Patients with Class III or IV heart disease (according to NYHA classification)
• Patients with a body weight < 110 lbs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + IFA administered in one skin location 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: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: IFA; 2 mL administered half intradermally and half subcutaneously
Experimental: Arm B (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + PolyICLC vaccine administered 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: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: PolyICLC; 1 mL administered half intradermally and half subcutaneously
Experimental: Arm C (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide vaccine administered in one skin location that is rotated to different sites on an extremity clinically uninvolved with melanoma. Resiquimod will be applied to the vaccine site immediately after the vaccine administration. Vaccines will be administered on Days 1, 8, 15, 36, 57, and 78.	Biological: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: Resiquimod; 500 mg applied to vaccine site after vaccine administration
Experimental: Arm D (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + PolyICLC vaccines administered in one skin location that is rotated to different sites on an extremity clinically uninvolved with melanoma. Resiquimod will be applied to the vaccine site immediately after vaccine administration. Vaccines will be administered on Days 1, 8, 15, 36, 57, and 78.	Biological: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: PolyICLC; 1 mL administered half intradermally and half subcutaneously; Other: Resiquimod; 500 mg applied to vaccine site after vaccine administration
Experimental: Arm E (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + IFA + PolyICLC vaccines administered 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: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: IFA; 2 mL administered half intradermally and half subcutaneously; Other: PolyICLC; 1 mL administered half intradermally and half subcutaneously
Experimental: Arm F (Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + IFA vaccines administered in one skin location that is rotated to different sites on an extremity clinically uninvolved with melanoma. Resiquimod will be applied to the vaccine site immediately after vaccine administration. Vaccines will be administered on Days 1, 8, 15, 36, 57, and 78.	Biological: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: IFA; 2 mL administered half intradermally and half subcutaneously; Other: Resiquimod; 500 mg applied to vaccine site after vaccine administration
Experimental: Arm G(Part 1); Peptide Vaccine (LPV7) + Tetanus peptide + PolyICLC + IFA vaccines administered in one skin location that is rotated to different sites on an extremity clinically uninvolved with melanoma. Resiquimod will be applied to the vaccine site immediately after vaccine administration. Vaccines will be administered on Days 1, 8, 15, 36, 57, and 78.	Biological: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: IFA; 2 mL administered half intradermally and half subcutaneously; Other: PolyICLC; 1 mL administered half intradermally and half subcutaneously; Other: Resiquimod; 500 mg applied to vaccine site after vaccine administration
Experimental: Arm E2; Peptide Vaccine (LPV7) + IFA + PolyICLC vaccines administered in one skin location. Each vaccine will be administered in the same skin site for all 6 vaccines. Vaccines will be administered on Days 1, 8, 15, 36, 57, and 78.	Biological: Peptide Vaccine (LPV7) + Tetanus peptide; 1.5 mL administered half intradermally and half subcutaneously.; Other: IFA; 2 mL administered half intradermally and half subcutaneously; Other: PolyICLC; 1 mL administered half intradermally and half subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events Per Study Arm	Safety and toxicity following vaccination with 7 long peptides in melanoma patients with and without TLR agonists. Patients are evaluated by safety labs and physical exams to assess for toxicity.	6 months
T Cell Response in Peripheral Blood Over Duration of Study Participation	Levels of peptide-reactive CD8+ T cells in the peripheral blood: number of participants with T cell response to minimal epitope for CD8 T cells. This was assessed by direct (ex vivo) IFN-gamma ELIspot assay for reactivity to known minimal epitopes. To be considered positive, there had to be an increase compared to the maximum negative control target by at least 2-fold and by at least 20 IFN-gamma secreting cells per 100,000 CD8 T cells evaluated.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T Cell Response and Function in Peripheral Blood	CD4+ T cell responses to peptides in the vaccine, and their function	6 months

Collaborators and Investigators

• Sponsor: Craig L Slingluff, Jr
• Collaborators: University of Virginia
• Investigators: Principal Investigator: Craig L Slingluff, Jr., M.D., University of Virginia

Publications and helpful links

General Publications

• Patel SP, Petroni GR, Roszik J, Olson WC, Wages NA, Chianese-Bullock KA, Smolkin M, Varhegyi N, Gaughan E, Smith KT, Haden K, Hall EH, Gnjatic S, Hwu P, Slingluff CL. Phase I/II trial of a long peptide vaccine (LPV7) plus toll-like receptor (TLR) agonists with or without incomplete Freund's adjuvant (IFA) for resected high-risk melanoma. J Immunother Cancer. 2021 Aug;9(8):e003220. doi: 10.1136/jitc-2021-003220.

Helpful Links

• NCI website

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimated): April 30, 2014

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic melanoma; neoplasms; melanoma; adjuvants; Poly ICLC; Freund's Adjuvant; resiquimod; peptide vaccine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; Poly ICLC
• Other Study ID Numbers: 15931; MEL60 (Other Identifier: UVA Human Immune Therapy Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No