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

Study Overview
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Brief Summary
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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.

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

Conditions
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Melanoma, Metastatic Melanoma, Mucosal Melanoma

Intervention / Treatment
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* Biological: Peptide Vaccine (LPV7) + Tetanus peptide
* Other: PolyICLC
* Other: Resiquimod
* Other: IFA


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: IFA<br>* 2 mL administered half intradermally and half subcutaneously<br>|
| Experimental: Arm B (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: PolyICLC<br>* 1 mL administered half intradermally and half subcutaneously<br>|
| Experimental: Arm C (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: Resiquimod<br>* 500 mg applied to vaccine site after vaccine administration<br>|
| Experimental: Arm D (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: PolyICLC<br>* 1 mL administered half intradermally and half subcutaneously<br>Other: Resiquimod<br>* 500 mg applied to vaccine site after vaccine administration<br>|
| Experimental: Arm E (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: PolyICLC<br>* 1 mL administered half intradermally and half subcutaneously<br>Other: IFA<br>* 2 mL administered half intradermally and half subcutaneously<br>|
| Experimental: Arm F (Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: Resiquimod<br>* 500 mg applied to vaccine site after vaccine administration<br>Other: IFA<br>* 2 mL administered half intradermally and half subcutaneously<br>|
| Experimental: Arm G(Part 1)<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: PolyICLC<br>* 1 mL administered half intradermally and half subcutaneously<br>Other: Resiquimod<br>* 500 mg applied to vaccine site after vaccine administration<br>Other: IFA<br>* 2 mL administered half intradermally and half subcutaneously<br>|
| Experimental: Arm E2<br>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<br>* 1.5 mL administered half intradermally and half subcutaneously.<br>Other: PolyICLC<br>* 1 mL administered half intradermally and half subcutaneously<br>Other: IFA<br>* 2 mL administered half intradermally and half subcutaneously<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, neoplasms, Poly ICLC, Freund's Adjuvant, Metastatic melanoma, resiquimod, adjuvants, peptide vaccine