Metastatic MelanomaPhase 2NCT01042366
Dendritic Cells (DC) Vaccine for Metastatic Melanoma
A Phase 2 study testing Vaccination in people with Metastatic Melanoma, run by John Kirkwood at 1 site in United States.
Trial summary
The purpose of this study is to determine what effect using an experimental tumor vaccine (a substance or group of substances meant to cause the immune system to respond to a tumor) made using patients' own tumor cells and blood cells will have on their melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Vaccination
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2002to Nov 2014
- Phase
- Phase 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
- Subjects must have Stage III-IV melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC). Each diagnosis will be confirmed by pathology review at the Melanoma Center of the University of Pittsburgh Cancer Institute.
- All subjects have to be HLA-A2 positive (required for immunologic testing).
- Subjects must have recovered fully from surgery.
- Availability of resectable or tissue banked tumor cells for autologous tumor dendritic cell vaccine preparation.
- Sufficient number of tumor cells available for autologous tumor dendritic cell vaccine preparation (min 2.6 x 10 7).
- Sufficient number of DCs of at least 12 X 10 6 for preparation of the autologous tumor dendritic cell vaccine preparation (if less than needed number of cells will be obtained by one course of leukopheresis, the second leukopheresis will be repeated 2 weeks apart).
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- Subjects must not have received any chemotherapy or immunotherapy within the four weeks preceding vaccination (six weeks for nitrosourea, mitomycin).
- Subjects must have an expected survival of greater than or equal to 12 months.
- Subjects must have an ECOG performance status 0 or 1.
- Subjects must have the following initial and subsequent pretreatment
- laboratory parameters: Granulocytes >=2,500/mm3 Lymphocytes >=1000/mm3 Platelets >100,000/mm3 Serum Creatinine <=1.5 X the ULN AST, ALT, GGT, LDH, Alk phos <= 2.5 X the ULN Serum Bilirubin <=1.5 X ULN
- Subjects must be >= 18 years of age and must be able to understand the written informed consent.
- No evidence of active infection, regardless of the degree of severity or localization. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
- Subjects with measurable disease must have an evaluation for extent of disease (tumor staging) performed within 30 days of start of treatment.
- Pretreatment baseline evaluations for laboratory parameters must be obtained within 10 to18 days of subject registration
Who cannot join
- Subjects currently treated with anti inflammatory agents including glucocorticoid therapy are ineligible.
- Subjects currently on treatment with steroids are ineligible, but may receive the DC autologous tumor dendritic cell vaccine 4 weeks after steroid cessation. Subjects on maintenance steroids because of adrenal insufficiency are eligible.
- Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT, Alk.Phos, LDH, and total bilirubin greater than 2 X ULN].
- Subjects with uncontrolled pain.
- Subjects with autoimmune disease, HIV, and hepatitis
- Subjects with symptomatic brain metastasis.
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- Subjects with active prior malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix).
- Subjects who have been previously immunized with melanoma vaccine until 10 subjects have been registered in each treatment arm.
- Subjects who are pregnant.
- Subjects who have sensitivity to drugs to provide local anesthesia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Metastatic Melanoma Using Autologous Mature Dendritic Cells
The purpose of this study is to determine what effect using an experimental tumor vaccine (a substance or group of substances meant to cause the immune system to respond to a tumor) made using patients' own tumor cells and blood cells will have on their melanoma.
Read the detailed description
Historically, metastatic melanoma has been associated with a poor prognosis. Recently, numerous immunotherapeutic agents, particularly checkpoint inhibitors, have moved to the forefront of therapy. Checkpoint inhibitors such as ipilimumab, pembrolizumab, and nivolumab have revolutionized the treatment of melanoma. Despite this, not all patients respond to checkpoint inhibitors, and even patients who initially respond to checkpoint inhibitor therapy often later relapse (median response duration of 2 years); complete responses remain uncommon. Thus, more effective immunotherapies are clearly needed.
The concept of administering dendritic cell (DC)-based vaccines to prompt an immune response against tumor cells has shown promise in the treatment of advanced cancers. Sipuleucel-T, now FDA-approved for the treatment of advanced prostate cancer, is one such vaccine that consists of autologous antigen-presenting cell (APC) activated ex vivo by a fusion protein consisting of the antigen prostatic acid phosphatase (PAP) and granulocyte-macrophage colony stimulating factor (GM-CSF). Although response rates to Sipuleucel-T are low, recent studies suggest that DC vaccines have the potential to improve survival by increasing the breadth and diversity of melanoma-specific T cells.
It is known that the method of antigen (Ag) delivery is important for the success of DC vaccines, but it remains unclear which method is most effective in producing antitumor responses. Approaches tested clinically include pulsing with HLA-restricted defined peptide Ags, loading with purified proteins, transfecting with mRNA, engineering with Ag-encoding viral vectors, and using autologous tumor cells or allogeneic cell lines directly as sources of Ag. Efficacy can be measured in vivo using surrogate endpoints, such as development of tumor-specific delayed-type hypersensitivity (DTH) reactions. Prolonged survival of vaccinated melanoma patients has been reported to correlate with induction of positive DTH tests. Antitumor activity may also be assessed by ELISpot analysis of the frequency of tumor-Ag specific IFNγ-producing T cells. To assess the quality of the DC vaccines, surrogate markers of DC function including maturation markers, co-stimulatory molecule expression, and IL12p70 production, a critical cytokine in antitumor response, can be measured
- Conditions
- Metastatic Melanoma
- Being tested
- Vaccination
- Keywords
- Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VaccinationBiological
Subjects will receive as an outpatient 4 weekly ultrasound-guided intra/peri-lymph nodal administrations of the autologous tumor dendritic cell vaccine. The dose of the autologous tumor cell dendritic cells/vaccine will be 1-5 X 106.
| Study group | Role | What they receive |
|---|---|---|
| Vaccine co-cultured with melanoma cells | Experimental | Dendritic Cells co-cultured with melanoma cells injected as a vaccine intra/peri-nodally under ultrasound guidance Receives: Biological: Vaccination |
| Vaccine pulsed with tumor cell lysates | Experimental | Dendritic Cells pulsed with tumor cell lysates were injected as a vaccine intra/peri-nodally under ultrasound guidance Receives: Biological: Vaccination |
| Vaccine fused with tumor cells | Experimental | Dendritic Cells fused with tumor cells were injected as a vaccine intra/peri-nodally under ultrasound guidance Receives: Biological: Vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delayed Type Hypersensitivity (DTH) Response
Delayed type hypersensitivity (DTH) response to antigen-loaded autologous, dendritic cell vaccine (DC) injected intradermal in vivo
Measured: 12 mo
ELISpot Response to Melanoma
Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, and HLA-presented melanoma epitopes, using ELISPOT and MHC-peptide tetramer assays.
Measured: 12 mo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2010 (estimated)
- Study startOct 2002
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: Closed to accrual in March 2009 for slow accrual.
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 Metastatic 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Kirkwood
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, John Kirkwood, University of Pittsburgh
- Investigators
- John M Kirkwood, MD, Principal investigator, UPMC UPCI HCC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01042366
- Sponsor's protocol ID
- UPCI 01-171
- Other IDs
- 5P01CA073743
- Status last verified
- Jul 2017
- First submitted
- 4 Jan 2010
- Last updated
- 16 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Evaluation of Immunization Against Tumor Cells in Subjects With Metastatic Melanoma Using Autologous Mature Dendritic Cells
- ClinicalTrials.gov ID
- NCT01042366
- Acronym / sponsor ID
- UPCI 01-171
- Conditions
- Metastatic Melanoma
- Keywords
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed to accrual in March 2009 for slow accrual.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- John KirkwoodUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- Oct 2002
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 5 Jan 2010 (estimated)
- Results
- Posted 16 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine what effect using an experimental tumor vaccine (a substance or group of substances meant to cause the immune system to respond to a tumor) made using patients' own tumor cells and blood cells will have on their melanoma.
Detailed description
Historically, metastatic melanoma has been associated with a poor prognosis. Recently, numerous immunotherapeutic agents, particularly checkpoint inhibitors, have moved to the forefront of therapy. Checkpoint inhibitors such as ipilimumab, pembrolizumab, and nivolumab have revolutionized the treatment of melanoma. Despite this, not all patients respond to checkpoint inhibitors, and even patients who initially respond to checkpoint inhibitor therapy often later relapse (median response duration of 2 years); complete responses remain uncommon. Thus, more effective immunotherapies are clearly needed.
The concept of administering dendritic cell (DC)-based vaccines to prompt an immune response against tumor cells has shown promise in the treatment of advanced cancers. Sipuleucel-T, now FDA-approved for the treatment of advanced prostate cancer, is one such vaccine that consists of autologous antigen-presenting cell (APC) activated ex vivo by a fusion protein consisting of the antigen prostatic acid phosphatase (PAP) and granulocyte-macrophage colony stimulating factor (GM-CSF). Although response rates to Sipuleucel-T are low, recent studies suggest that DC vaccines have the potential to improve survival by increasing the breadth and diversity of melanoma-specific T cells.
It is known that the method of antigen (Ag) delivery is important for the success of DC vaccines, but it remains unclear which method is most effective in producing antitumor responses. Approaches tested clinically include pulsing with HLA-restricted defined peptide Ags, loading with purified proteins, transfecting with mRNA, engineering with Ag-encoding viral vectors, and using autologous tumor cells or allogeneic cell lines directly as sources of Ag. Efficacy can be measured in vivo using surrogate endpoints, such as development of tumor-specific delayed-type hypersensitivity (DTH) reactions. Prolonged survival of vaccinated melanoma patients has been reported to correlate with induction of positive DTH tests. Antitumor activity may also be assessed by ELISpot analysis of the frequency of tumor-Ag specific IFNγ-producing T cells. To assess the quality of the DC vaccines, surrogate markers of DC function including maturation markers, co-stimulatory molecule expression, and IL12p70 production, a critical cytokine in antitumor response, can be measured
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vaccine co-cultured with melanoma cells | Experimental | Biological: VaccinationDendritic Cells co-cultured with melanoma cells injected as a vaccine intra/peri-nodally under ultrasound guidance |
| Vaccine pulsed with tumor cell lysates | Experimental | Biological: VaccinationDendritic Cells pulsed with tumor cell lysates were injected as a vaccine intra/peri-nodally under ultrasound guidance |
| Vaccine fused with tumor cells | Experimental | Biological: VaccinationDendritic Cells fused with tumor cells were injected as a vaccine intra/peri-nodally under ultrasound guidance |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must have Stage III-IV melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC). Each diagnosis will be confirmed by pathology review at the Melanoma Center of the University of Pittsburgh Cancer Institute.
- All subjects have to be HLA-A2 positive (required for immunologic testing).
- Subjects must have recovered fully from surgery.
- Availability of resectable or tissue banked tumor cells for autologous tumor dendritic cell vaccine preparation.
- Sufficient number of tumor cells available for autologous tumor dendritic cell vaccine preparation (min 2.6 x 10 7).
Key exclusion criteria (10 listed)
- Subjects currently treated with anti inflammatory agents including glucocorticoid therapy are ineligible.
- Subjects currently on treatment with steroids are ineligible, but may receive the DC autologous tumor dendritic cell vaccine 4 weeks after steroid cessation. Subjects on maintenance steroids because of adrenal insufficiency are eligible.
- Subjects with severely abnormal liver function tests [AST (SGOT), ALT (SGPT), GGT, Alk.Phos, LDH, and total bilirubin greater than 2 X ULN].
- Subjects with uncontrolled pain.
- Subjects with autoimmune disease, HIV, and hepatitis
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 |
|---|---|---|
| VaccinationSubjects will receive as an outpatient 4 weekly ultrasound-guided intra/peri-lymph nodal administrations of the autologous tumor dendritic cell vaccine. The dose of the autologous tumor cell dendritic cells/vaccine will be 1-5 X 106. | Biological | Vaccine co-cultured with melanoma cells, Vaccine fused with tumor cells, Vaccine pulsed with tumor cell lysates |
Primary outcome
Delayed Type Hypersensitivity (DTH) Response
Time frame: 12 mo
Delayed type hypersensitivity (DTH) response to antigen-loaded autologous, dendritic cell vaccine (DC) injected intradermal in vivo
ELISpot Response to Melanoma
Time frame: 12 mo
Peripheral blood CD8+ and CD4+ T cell responses against autologous tumor cells, and HLA-presented melanoma epitopes, using ELISPOT and MHC-peptide tetramer assays.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2017.
- 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.
John M Kirkwood, MD principal investigator
UPMC UPCI HCC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vaccination in people with Metastatic Melanoma, run by John Kirkwood 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 15 inclusion and 10 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 16 Aug 2017. 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 phase mean?
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 16 Aug 2017). 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?
Delayed Type Hypersensitivity (DTH) Response (time frame: 12 mo). 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 16 Aug 2017.