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

Phase 1

Completed

Conditions: Metastatic Melanoma
Mucosal Melanoma
Melanoma

Interventions: Biological: Peptide Vaccine (LPV7) + Tetanus peptide
Other: PolyICLC
Other: IFA
Other: Resiquimod

Registration Number: NCT02126579

Lead Sponsor: Craig L Slingluff, Jr

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B (Part 1)	PolyICLC	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.
Arm E (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm E (Part 1)	IFA	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.
Arm D (Part 1)	PolyICLC	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.
Arm G(Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm A (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm A (Part 1)	IFA	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.
Arm B (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm D (Part 1)	Resiquimod	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.
Arm E (Part 1)	PolyICLC	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.
Arm F (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm F (Part 1)	IFA	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.
Arm C (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm C (Part 1)	Resiquimod	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.
Arm D (Part 1)	Peptide Vaccine (LPV7) + Tetanus peptide	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.
Arm G(Part 1)	PolyICLC	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.
Arm G(Part 1)	Resiquimod	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.
Arm G(Part 1)	IFA	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.
Arm F (Part 1)	Resiquimod	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.
Arm E2	PolyICLC	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.
Arm E2	IFA	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.
Arm E2	Peptide Vaccine (LPV7) + Tetanus peptide	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.

Primary Outcome Measures

Name	Time	Method
T Cell Response in Peripheral Blood Over Duration of Study Participation	6 months	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.
Number of Participants With Treatment-related Adverse Events Per Study Arm	6 months	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.

Secondary Outcome Measures