A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma

NCT02385669 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 17780
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether it is safe to administer a peptide vaccine with ipilimumab. This study will also evaluate the effects of the combination of the peptide vaccine and ipilimumab on the immune system. The investigators will monitor these effects by performing tests in the laboratory on participants' blood, a lymph node, and tumor samples.

Conditions

Melanoma

Keywords

vaccine; peptide; ipilimumab; Yervoy; Montanide ISA-51

Outcome Measures

Primary Outcomes (2)

• Safety (Adverse Event Profile)

  Adverse event profile for the combination of ipilimumab and 6MHP

  30 days after the last vaccination

• CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node

  CD4+ T cell responses to the peptide vaccine, defined as: 1. any CD4+ T cell response to 6 melanoma helper peptides (6MHP) in peripheral blood mononuclear cells (PBMC) with a 10 fold (or greater) increase in response over background (high response) by ex vivo ELIspot assay. 2. CD4+ T cell high responses to 6MHP in PBMC at at least 2 consecutive time points having peripheral blood mononuclear cells (PBMC) with a 10 fold (or greater) increase in response over background by ex vivo ELIspot assay. 3. CD4+ T cell high response to 6MHP in sentinel immunized lymph node (SIN).

  through day 92

Secondary Outcomes (1)

• Epitope Spreading (Epitope-spreading for CD8+ T Cells in the Blood and the Sentinel Immunized Node)

  through day 92

Study Arms (1)

6MHP and ipilimumab

EXPERIMENTAL

The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 43, 64, and 85. All peptide vaccines are administered intradermally and subcutaneously. Ipilimumab will be administered in accord with the official prescribing information: 3 mg/kg intravenously once every 3 weeks, for 4 doses. Ipilimumab will be administered on days 1, 22, 43, and 64.

Drug: Ipilimumab; Biological: 6MHP

Interventions

Ipilimumab DRUG

Checkpoint blockade inhibitor

Also known as: Yervoy

6MHP and ipilimumab

6MHP BIOLOGICAL

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

Also known as: 6 melanoma helper peptide vaccine

6MHP and ipilimumab

Eligibility Criteria

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

You may qualify if:

• Participants with stage IIA (with class 2 DecisionDx Score) through IV melanoma in cohorts defined below. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. The diagnosis of melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC staging system. Participants must be eligible to be treated with ipilimumab based on clinician judgment within standard of care.
• Cohort 1 (Advanced Patients): unresectable stage III or IV melanoma that have clinical or radiographic evidence of disease.
• Cohort 2 (Neoadjuvant therapy): primary melanoma with clinically apparent lymph node or in transit/satellite lesions with or without lymph node involvement, in transit recurrence or metastatic recurrence amenable to complete resection to no evidence of disease
• Cohort 3 (Adjuvant therapy): Stage IIA (with class 2 DecisionDx Score), IIB-IV melanoma resected to no evidence of disease.
• Participants will be required to have radiological studies to define radiologically evident disease. Required studies include:
• Chest CT scan,
• Abdominal and pelvic CT scan, and
• Head CT scan or MRI PET/CT fusion scan may replace scans of the chest, abdomen, and pelvis.
• Participants who have melanoma available for biopsy pre-treatment and on day 22 must consent to having those biopsies. Melanoma lesions may be in nodes, skin, soft tissue, liver, or other sites that can be accessed by core needle biopsy, or incisional or excisional biopsy, with or without image guidance.
• Participants who have had brain metastases will be eligible if all of the following are true:
• Each brain metastasis must have been treated by surgical removal, stereotactic radiosurgery or managed to complete resolution with immunotherapy. Patients with brain lesions managed by immunotherapy without excision or radiosurgery are included provided that the brain metastases have completely resolved after systemic therapy and there are no neurologic symptoms or need for systemic therapy to control CNS-disease related symptoms.
• There has been no evident growth of any brain metastasis since the most recent treatment. If a patient has been managed by immunotherapy alone, the prior lesions must be completely resolved.
• No brain metastasis is \> 2 cm in diameter at the time of registration
• The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week prior to registration.
• ECOG performance status of 0 or 1

You may not qualify if:

• Participants who have received 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 prior to registration)
• Allergy desensitization injections
• High doses of systemic corticosteroids, with the following qualifications and exceptions:
• Daily doses of 10 mg predisone (or equivalent) per day administered parenterally or orally are not allowed in patients with normal adrenal and pituitary function.
• In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed.
• Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent).
• Topical and nasal corticosteroids are acceptable.
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational medication
• Targeted therapies specific for mutated BRAF or for MEK
• HIV positivity or evidence of active Hepatitis C virus (testing to be done within 6 months of study entry).

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead

Study Sites (1)

Cancer Center at the University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Craig L. Slingluff, Jr. MD
• Organization: University of Virginia

cls8h@virginia.edu

434-924-9311

Study Officials

• Elizabeth Gaughan, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Craig L. Slingluff, Jr., MD

  University of Virginia

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 11, 2015
• Study Start: April 1, 2015
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: May 5, 2020
• Results First Posted: June 26, 2019

Record last verified: 2020-04

Locations

US (1)