MelanomaPhase 1/2Mel62; 6PACNCT02385669
A Phase I/II Trial to Evaluate a Peptide Vaccine Plus Ipilimumab in Patients With Melanoma
A Phase 1/2 study testing Ipilimumab and 6MHP in people with Melanoma, run by Craig L Slingluff, Jr at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Ipilimumab and 6MHP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 18 Sep 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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
Who cannot join
- 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:
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- 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:
- was discontinued early for toxicity, or
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Center at the University of Virginia
Charlottesville, Virginia, 22908
About this study
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)
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
- Being tested
- Ipilimumab, 6MHP
- Keywords
- vaccine, peptide, ipilimumab, Yervoy, Montanide ISA-51
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Checkpoint blockade inhibitor
6MHPBiological
Also called 6 melanoma helper peptide vaccine
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ipilimumab; Biological: 6MHP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Adverse Event Profile)
Adverse event profile for the combination of ipilimumab and 6MHP
Measured: 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:
- 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.
- 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.
- CD4+ T cell high response to 6MHP in sentinel immunized lymph node (SIN).
Measured: through day 92
Secondary outcomes (1)
Epitope Spreading (Epitope-spreading for CD8+ T Cells in the Blood and the Sentinel Immunized Node)
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.
Measured: through day 92
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study startApr 2015
- Primary completion18 Sep 2019
- Study completion18 Sep 2019
Why it stopped: why study stopped
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig L Slingluff, Jr
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Craig L Slingluff, Jr, University of Virginia
- Investigators
- Elizabeth Gaughan, MD, Principal investigator, University of VirginiaCraig L. Slingluff, Jr., MD, Study director, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02385669
- Sponsor's protocol ID
- 17780
- Acronym
- Mel62; 6PAC
- Status last verified
- Apr 2020
- First submitted
- 5 Mar 2015
- Last updated
- 5 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02385669
- Acronym / sponsor ID
- Mel62; 6PAC / 17780
- Conditions
- Melanoma
- Keywords
- vaccine, peptide, ipilimumab, Yervoy, Montanide ISA-51
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: why study stopped
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Craig L Slingluff, JrUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- 18 Sep 2019 (actual)
- Study completion
- 18 Sep 2019 (actual)
- First posted
- 11 Mar 2015 (estimated)
- Results
- Posted 26 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6MHP and ipilimumab | Experimental | Drug: Ipilimumab, Biological: 6MHPThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
- Participants will be required to have radiological studies to define radiologically evident disease. Required studies include:
- 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:
- ECOG performance status of 0 or 1
Key exclusion criteria (44 listed)
- Participants who have received the following medications or treatments at any time within 4 weeks of registration:
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabAlso: YervoyCheckpoint blockade inhibitor | Drug | 6MHP and ipilimumab |
| 6MHPAlso: 6 melanoma helper peptide vaccine6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides | Biological | 6MHP and ipilimumab |
Primary outcome
Safety (Adverse Event Profile)
Time frame: 30 days after the last vaccination
Adverse event profile for the combination of ipilimumab and 6MHP
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).
1 secondary outcome
Epitope Spreading (Epitope-spreading for CD8+ T Cells in the Blood and the Sentinel Immunized Node)
Time frame: through day 92
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Gaughan, MD principal investigator
University of Virginia
Craig L. Slingluff, Jr., MD study director
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ipilimumab and 6MHP in people with Melanoma, run by Craig L Slingluff, Jr at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Adverse Event Profile) (time frame: 30 days after the last vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2020.