Metastatic MelanomaPhase 2NCT00203879
Study of MAGE-3/Melan-A/gp 100/NA17 and rhIL-12 With/Out Low Dose IL-2 in Metastatic Melanoma
A Phase 2 study testing MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) and MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 in people with Metastatic Melanoma, run by University of Chicago at 1 site in United States.
Trial summary
Purpose of investigation: Primary hypotheses: Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8+ T cells against all 4 antigens simultaneously. Immunization with 4 melanoma antigen peptides will increase the response rate from 10% to 30%. 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?
- MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) and MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2002to May 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Histologically-confirmed melanoma with evidence of metastatic disease, either by radiologic or physical examination. In transit metastases are allowed. Biopsy should be performed to reconfirm the diagnosis in cases of doubt.
- Life expectancy of at least 12 weeks.
- Karnofsky performance status index >/=70.
- Written informed consent
- Adequate hematopoietic, renal, and hepatic function
- LDH <1.25 x ULN
- HLA typing: patient must express HLA-A2.
- Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells.
Who cannot join
- Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention.
- Pregnant or nursing women.
- Biological therapy in the 4 weeks prior to the start of dosing.
- Prior therapy with a melanoma vaccine containing MAGE-3, Melan-A, gplOO, NA17 peptides.
- Patients with intrinsic immunosuppression, including seropositivity for HIV antibody. Patient should be tested if risk factors are identified.
- Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C.
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- Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A).
- Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent.
- Active or history of autoimmune disease including but not limited to: rheumatoid arthritis (RF-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosis (clinical evidence with ANA 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura.
- Active gastrointestinal bleeding or uncontrolled peptic ulcer disease. Presence of untreated brain metastases. All patients must undergo brain imaging as part of the pre-study evaluation. Only patients with no brain metastases, or with brain lesions successfully treated by stereotactic radiation or surgical removal without recurrence at 28 day follow-up, will be eligible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Study of Immunization With MAGE-3/Melan-A/gp 100/NA17 Peptide-Pulsed Autologous PBMC and rhIL-12 With or Without Low Dose IL-2 Inpatients With Metastatic Melanoma
Purpose of investigation: Primary hypotheses: Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8+ T cells against all 4 antigens simultaneously. Immunization with 4 melanoma antigen peptides will increase the response rate from 10% to 30%. Administration of low-dose IL-2 following each vaccine will result in a greater than 3-fold increase in specific T cells compared to no IL-2.
Secondary hypotheses: Immunization will clear the blood of detectable circulating melanoma cells. Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens, class I MHC, or the TAP peptide transporter, or may fail to show increased expression of mRNA for IFN-y or perforin. Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination.
Read the detailed description
Based on the above preclinical and Phase I results, a logical strategy for a second generation melanoma vaccine has emerged. A randomized Phase II study in metastatic melanoma patients will be undertaken. Patients first will be HLA-typed; HLA-A2-positive patients will be eligible for screening. When feasible, each patient will undergo a tumor biopsy to screen for expression of MAGE-3, Melan-A, gplOO, and NAI 7 using RT-PCR and immunohistochemistry, to determine whether T cells are present in the lesion, to measure cytokine gene expression by RT-PCR, and to perform gene array analysis. In addition, blood cells will be analyzed for certain parameters of T cell function.
Patients will be randomized to cohorts A (no IL-2) or B (with low-dose IL-2). For treatment, peripheral blood will be collected and fractionated by density centrifugation to isolate PBMC as a source of APC. The PBMC will be divided into four pools, each of which will be incubated with one of the following peptides: MAGE-3, Melan-A, gp 100, or Ni 7A. The peptide-loaded cells will then be washed and recombined into a single suspension in PBS, and lethally irradiated. Approximately 120 x 106 pulsed cells will be injected subcutaneously at a site near a lymph node not thought to be involved with tumor. The subcutaneous route has been selected for the reasons of safety, efficacy in the preclinical model, and the goal of targeting the vaccine to a draining lymph node. rhIL-12 (4 .tg straight dose) will then be given subcutaneously adjacent to the vaccine site days 1,3, and 5 of each cycle. This dose and schedule was found to be effective in our phase I study. In one-half of the patients (cohort B), IL-2 (I MU straight dose) will be administered subcutaneously daily, days 7-18. Re-immunization along with rhIL-12 followed by IL-2 (if assigned) will be performed at 3 week intervals as in cycle I.
On day 1 of each cycle, peripheral blood will be collected to measure peptide-specific IFN-y production. Before treatment and after every 3 cycles, PBMC will be collected to quantify peptide specific CD8 T cells by flow cytometric analysis with peptide/HLA-A2 tetramers, and evidence for a molecular response will be assessed by performing RT-PCR. for melanoma antigens on peripheral blood samples. In addition, prior to treatment, after the first 3 cycles, and at the time of going off- study, a tumor biopsy will be performed to assess the immune response in the tumor microenvironment, including gene array analysis. It is hoped that these studies will uncover the reason for lack of clinical response in patients with residual tumors. Clinical response will be assessed as a secondary outcome.
- Conditions
- Metastatic Melanoma
- Being tested
- MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug), MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2
- Keywords
- metastatic melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug)Drug
Also called draft
draft
MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2Drug
MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 Receives: Drug: MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) |
| 2 | Experimental | MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 without IL-2 Receives: Drug: MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary hypothesis is immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-.-producing CD8+ T cells against all 4 antigens simultaneously, and to determine the clinical response rate.
Measured: draft
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startFeb 2002
- Primary completionMay 2006
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Gajewski, M.D., Ph.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00203879
- Sponsor's protocol ID
- 11447A
- Status last verified
- Sep 2013
- First submitted
- 12 Sep 2005
- Last updated
- 5 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of Immunization With MAGE-3/Melan-A/gp 100/NA17 Peptide-Pulsed Autologous PBMC and rhIL-12 With or Without Low Dose IL-2 Inpatients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00203879
- Acronym / sponsor ID
- 11447A
- Conditions
- Metastatic Melanoma
- Keywords
- metastatic melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- Feb 2002
- Primary completion
- May 2006 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose of investigation: Primary hypotheses: Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8+ T cells against all 4 antigens simultaneously. Immunization with 4 melanoma antigen peptides will increase the response rate from 10% to 30%. Administration of low-dose IL-2 following each vaccine will result in a greater than 3-fold increase in specific T cells compared to no IL-2.
Secondary hypotheses: Immunization will clear the blood of detectable circulating melanoma cells. Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens, class I MHC, or the TAP peptide transporter, or may fail to show increased expression of mRNA for IFN-y or perforin. Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination.
Detailed description
Based on the above preclinical and Phase I results, a logical strategy for a second generation melanoma vaccine has emerged. A randomized Phase II study in metastatic melanoma patients will be undertaken. Patients first will be HLA-typed; HLA-A2-positive patients will be eligible for screening. When feasible, each patient will undergo a tumor biopsy to screen for expression of MAGE-3, Melan-A, gplOO, and NAI 7 using RT-PCR and immunohistochemistry, to determine whether T cells are present in the lesion, to measure cytokine gene expression by RT-PCR, and to perform gene array analysis. In addition, blood cells will be analyzed for certain parameters of T cell function.
Patients will be randomized to cohorts A (no IL-2) or B (with low-dose IL-2). For treatment, peripheral blood will be collected and fractionated by density centrifugation to isolate PBMC as a source of APC. The PBMC will be divided into four pools, each of which will be incubated with one of the following peptides: MAGE-3, Melan-A, gp 100, or Ni 7A. The peptide-loaded cells will then be washed and recombined into a single suspension in PBS, and lethally irradiated. Approximately 120 x 106 pulsed cells will be injected subcutaneously at a site near a lymph node not thought to be involved with tumor. The subcutaneous route has been selected for the reasons of safety, efficacy in the preclinical model, and the goal of targeting the vaccine to a draining lymph node. rhIL-12 (4 .tg straight dose) will then be given subcutaneously adjacent to the vaccine site days 1,3, and 5 of each cycle. This dose and schedule was found to be effective in our phase I study. In one-half of the patients (cohort B), IL-2 (I MU straight dose) will be administered subcutaneously daily, days 7-18. Re-immunization along with rhIL-12 followed by IL-2 (if assigned) will be performed at 3 week intervals as in cycle I.
On day 1 of each cycle, peripheral blood will be collected to measure peptide-specific IFN-y production. Before treatment and after every 3 cycles, PBMC will be collected to quantify peptide specific CD8 T cells by flow cytometric analysis with peptide/HLA-A2 tetramers, and evidence for a molecular response will be assessed by performing RT-PCR. for melanoma antigens on peripheral blood samples. In addition, prior to treatment, after the first 3 cycles, and at the time of going off- study, a tumor biopsy will be performed to assess the immune response in the tumor microenvironment, including gene array analysis. It is hoped that these studies will uncover the reason for lack of clinical response in patients with residual tumors. Clinical response will be assessed as a secondary outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug)MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 |
| 2 | Experimental | Drug: MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 without IL-2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically-confirmed melanoma with evidence of metastatic disease, either by radiologic or physical examination. In transit metastases are allowed. Biopsy should be performed to reconfirm the diagnosis in cases of doubt.
- Life expectancy of at least 12 weeks.
- Karnofsky performance status index >/=70.
- Written informed consent
- Adequate hematopoietic, renal, and hepatic function
Key exclusion criteria (10 listed)
- Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention.
- Pregnant or nursing women.
- Biological therapy in the 4 weeks prior to the start of dosing.
- Prior therapy with a melanoma vaccine containing MAGE-3, Melan-A, gplOO, NA17 peptides.
- Patients with intrinsic immunosuppression, including seropositivity for HIV antibody. Patient should be tested if risk factors are identified.
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 |
|---|---|---|
| MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug)Also: draftdraft | Drug | 1 |
| MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 | Drug | 2 |
Primary outcome
The primary hypothesis is immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-.-producing CD8+ T cells against all 4 antigens simultaneously, and to determine the clinical response rate.
Time frame: draft
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2013.
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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.
Thomas Gajewski, M.D., Ph.D. principal investigator
University of Chicago
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 MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) and MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 in people with Metastatic Melanoma, run by University of Chicago 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 8 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: finished, as of the sponsor's last update on 5 Sep 2013. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary hypothesis is immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-.-producing CD8+ T cells against all 4 antigens simultaneously, and to determine the clinical response rate. (time frame: draft). 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 Sep 2013.