Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma

NCT03617328 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 20085
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates whether it is safe to administer a peptide vaccine (6MHP) with adjuvants and the CDX-1127 monoclonal antibody, and whether the adjuvants and the CDX-1127 monoclonal antibody boost immune responses to the vaccine. In this study, the adjuvants are Montanide ISA-51 and polyICLC. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and tissue from a vaccine site.

Conditions

Melanoma

Keywords

peptide; vaccine; adjuvant; 6MHP; polyICLC; varlilumab; CDX-1127; Montanide ISA-51

Outcome Measures

Primary Outcomes (2)

• Safety of CDX-1127 administered with a melanoma vaccine

  Number of participants with dose-limiting toxicities based on CTCAE v5.0

  30 days after receiving the last dose of study drug

• Immunogenicity-Percent of patients with persistent CD4+ T cell responses to the 6MHP vaccine

  Number of participants with CD4+ T cell responses to 6 MHP persisting to day 127 or later.

  Day 127 or Day 176 or both

Secondary Outcomes (5)

• Immunologic effect of CDX-1127 - Impact on regulatory T cells

  Day 22 and Day 85 (Note: Day 85 biopsy not required for participants whose Day 85 visit would be due after IRB approval of Protocol v12-03-2020)

• Immunologic effect of CDX-1127 - Percent of circulating regulatory T cells

  through day 176

• Immunogenicity - Frequency of circulating CD4+ Th1 responses

  through day 176

• Immunogenicity-Frequency of durable CD4+ Th1 memory responses

  Day 8 to Day 85

• Immunogenicity-Frequency of CD4+ Th1 memory responses

  Day 183

Study Arms (2)

Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127

EXPERIMENTAL

200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. CDX-1127 (3mg/kg) will be administered intravenously on days 1, 36, and 78.

Biological: 6MHP; Drug: Montanide ISA-51; Drug: polyICLC; Drug: CDX-1127

Arm B: 6MHP/Montanide ISA-51 + polyICLC

EXPERIMENTAL

200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176.

Biological: 6MHP; Drug: Montanide ISA-51; Drug: polyICLC

Interventions

6MHP BIOLOGICAL

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Also known as: 6 melanoma helper peptide vaccine

Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127; Arm B: 6MHP/Montanide ISA-51 + polyICLC

Montanide ISA-51 DRUG

Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant

Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127; Arm B: 6MHP/Montanide ISA-51 + polyICLC

polyICLC DRUG

polyICLC, local adjuvant

Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127; Arm B: 6MHP/Montanide ISA-51 + polyICLC

CDX-1127 DRUG

CDX-1127, anti-CD27 monoclonal antibody

Also known as: Varlilumab

Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127

Eligibility Criteria

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

You may qualify if:

• Patients with stage IIB, IIC, III, or IV melanoma at original diagnosis or at restaging after recurrence, rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
• Patients with small radiologic or clinical findings of an indeterminate nature may be eligible.
• Patients with high-risk stage IIA melanoma (by DecisionDx Melanoma test, Castle Biosciences, Inc., Friendswood, TX) may be eligible.
• Participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Diagnosis of melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on version 8 AJCC staging system.
• Participants who have had brain metastases will be eligible if all of the following are true:
• Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery.
• No brain metastasis is \> 2 cm in diameter at the time of registration.
• Any neurologic symptoms attributable to brain metastases have returned to baseline.There is no evidence of new or enlarging brain metastases.
• The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week and ≤ 6 months prior to registration.
• ECOG performance status of 0 or 1.
• Ability and willingness to give informed consent.
• Adequate organ function
• Age 18 years or older at registration.

You may not qualify if:

• The following medications or treatments at any time within 4 weeks of registration:
• Chemotherapy
• Interferon (e.g. Intron-A®)
• Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week and ≤ 6 months prior to registration)
• Allergy desensitization injections
• High doses of systemic corticosteroids
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational medication
• Targeted therapies specific for mutated BRAF or for MEK
• Nitrosoureas within 6 weeks of registration.
• Checkpoint molecule blockade therapy within 12 weeks of registration.
• Known or suspected allergies to any component of the vaccine.
• Previous vaccination with 6MHP.
• Prior treatment with CDX-1127 or other CD27 agonistic antibody.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• Celldex Therapeutics: collaborator

Study Sites (2)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

montanide ISA 51; varlilumab

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

Study Officials

• Craig L Slingluff, Jr., 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: Professor of Surgery; Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: August 6, 2018
• Study Start: November 13, 2018
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Starting 1 year after publication
• Access Criteria: The PI will review access requests. We may share files or share documents through a shared server.

Locations

US (2)