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

Craig L Slingluff, Jr

Status and phase: Completed; Phase 2; Phase 1

Conditions: Mucosal Melanoma; Melanoma; Metastatic Melanoma

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02126579

MEL60 (Other Identifier)

15931

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 8 patient groups

Arm A (Part 1)

Experimental group

Description:

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.

Treatment:

Other: IFA

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm B (Part 1)

Experimental group

Description:

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.

Treatment:

Other: PolyICLC

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm C (Part 1)

Experimental group

Description:

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.

Treatment:

Other: Resiquimod

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm D (Part 1)

Experimental group

Description:

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.

Treatment:

Other: Resiquimod

Other: PolyICLC

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm E (Part 1)

Experimental group

Description:

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.

Treatment:

Other: IFA

Other: PolyICLC

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm F (Part 1)

Experimental group

Description:

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.

Treatment:

Other: Resiquimod

Other: IFA

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm G(Part 1)

Experimental group

Description:

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.

Treatment:

Other: Resiquimod

Other: IFA

Other: PolyICLC

Biological: Peptide Vaccine (LPV7) + Tetanus peptide

Arm E2

Experimental group

Description:

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.

Treatment:

Other: IFA

Other: PolyICLC

Biological: Peptide Vaccine (LPV7) + Tetanus peptide