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

NCT02385669

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 17780
  • NCT ID: NCT02385669

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
IpilimumabYervoy6MHP and ipilimumab
6MHP6 melanoma helper peptide vaccine6MHP and ipilimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
6MHP and ipilimumabExperimentalThe 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.
  • Ipilimumab
  • 6MHP

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:

               -  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

          -  Ability and willingness to give informed consent

          -  Adequate lab function tests Age 18 years or older at registration.

          -  Participants must have at least two intact (undissected) axillary and/or inguinal
             lymph node basins

        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.

               -  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).

          -  Participants who are currently receiving nitrosoureas or who have received this
             therapy within the preceding 6 weeks

          -  Participants who are currently receiving a checkpoint molecule blockade therapy, or
             who have received this therapy within the preceding 6 weeks, with the following
             exceptions:

               -  Participants who have received a PD-1 blocking antibody (eg: pembrolizumab or
                  nivolumab) may be enrolled 3 weeks after receiving the last dose of that
                  antibody.

               -  Participants who have been treated previously with a CTLA-4 blocking antibody
                  either as monotherapy or as part of combination CTLA-4/PD-1 blockade will be
                  ineligible if CTLA-4 therapy:

                    1. was discontinued early for toxicity, or

                    2. did not induce stable disease or objective clinical response (by RECIST or
                       irRC criteria) lasting 6 months or more.

        Note: Patients may be eligible if they have experienced progression after a period of
        stable disease (6 months or more) or an objective clinical response (by irRC or RECIST) (6
        months or more) induced by CTLA-4 blockade or combination CTLA-4/PD-1 blockade.

        Note: Similar guidelines will apply for tremelimumab or other CTLA-4 blocking antibodies.

          -  Participants with known or suspected allergies to any component of the vaccine.

          -  Participants may not have been vaccinated previously with any of the synthetic
             peptides included in this protocol. Participants who have received vaccinations
             containing agents other than the synthetic peptides included in this protocol and have
             recurred during or after administration of the vaccine will be eligible to enroll 12
             weeks following their last vaccination.

          -  Pregnancy.

          -  Female participants must not be breastfeeding

          -  Participants in whom there is a medical contraindication or potential problem in
             complying with the requirements of the protocol in the opinion of the investigator.

          -  Participants classified according to the New York Heart Association classification as
             having Class III or IV heart disease.

        Participants with uncontrolled diabetes, defined as having a HGB-A1C> 7.5%.

          -  Participants must not have had prior autoimmune disorders requiring cytotoxic or
             immunosuppressive therapy, or autoimmune disorders with visceral involvement.
             Participants with an active autoimmune disorder requiring these therapies are also
             excluded. The following will not be exclusionary:

               -  The 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

               -  A history of immune-related adverse events with immune therapy, if they have
                  resolved completely.

          -  Participants who have another cancer diagnosis, except that the following diagnoses
             will be allowed:

               -  squamous cell cancer of the skin without known metastasis

               -  basal cell cancer of the skin without known metastasis

               -  carcinoma in situ of the breast (DCIS or LCIS)

               -  carcinoma in situ of the cervix

               -  any cancer without distant metastasis that has been treated successfully, without
                  evidence of recurrence or metastasis for over 2 years

          -  Participants with known addiction to alcohol or drugs who are actively taking those
             agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.

          -  Body weight < 110 pounds at registration, due to the amount and frequency with which
             blood will be drawn.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety (Adverse Event Profile)
Time Frame:30 days after the last vaccination
Safety Issue:
Description:Adverse event profile for the combination of ipilimumab and 6MHP

Secondary Outcome Measures

Measure:Epitope Spreading (Epitope-spreading for CD8+ T Cells in the Blood and the Sentinel Immunized Node)
Time Frame:through day 92
Safety Issue:
Description:An evaluation of epitope-spreading for CD8+ T cells in the blood and the sentinel immunized node that are reactive to a panel of defined melanoma antigens.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Craig L Slingluff, Jr

Trial Keywords

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

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