A Phase I/II Trial to Evaluate the Safety and Immunogenicity of a Helper Peptide Vaccine Plus CTLA-4 Blockade in Melanoma Patients (Mel62; 6PAC)
Overview
- Phase
- Phase 1
- Intervention
- Ipilimumab
- Conditions
- Melanoma
- Sponsor
- Craig L Slingluff, Jr
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Craig L Slingluff, Jr
Director, Human Immune Therapy Center
University of Virginia
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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.
Arms & Interventions
6MHP and ipilimumab
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.
Intervention: Ipilimumab
6MHP and ipilimumab
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.
Intervention: 6MHP
Outcomes
Primary Outcomes
CD4+ T Cell Responses in the Blood and in the Sentinel Immunized Node
Time Frame: through day 92
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).
Safety (Adverse Event Profile)
Time Frame: 30 days after the last vaccination
Adverse event profile for the combination of ipilimumab and 6MHP
Secondary Outcomes
- Epitope Spreading (Epitope-spreading for CD8+ T Cells in the Blood and the Sentinel Immunized Node)(through day 92)