Metastatic MelanomaPhase 1NCT00672542
Immunotherapy of Melanoma With Tumor Antigen RNA and Small Inhibitory RNA Transfected Autologous Dendritic Cells
A Phase 1 study testing Proteasome siRNA and tumor antigen RNA-transfected dendritic cells in people with Metastatic Melanoma and Absence of CNS Metastases, run by Scott Pruitt at 1 site in United States.
Trial summary
Transfection with siRNA targeting the immunoproteasome alters proteasome-mediated antigen processing by the dendritic cell, generating TAA-derived peptides that we hypothesize, based on preclinical results, will induce enhanced anti-melanoma immune responses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Absence of CNS Metastases
- What is being tested?
- Proteasome siRNA and tumor antigen RNA-transfected dendritic cells
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Jul 2013
- Phase
- Phase 1
- 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
- Patients with confirmed metastatic melanoma.
- Karnofsky performance status greater than or equal to 70%.
- Estimated life expectancy > 6 months.
- Age > 18 years.
- Adequate hematologic function
- Adequate renal and hepatic function
- Ability to understand and provide signed informed consent that fulfills Institutional Review Board guidelines.
- Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol.
Who cannot join
- Subjects undergoing concurrent chemotherapy, radiation therapy, or immunotherapy will be excluded.
- The subject has previously irradiated, surgically treated, or newly diagnosed central nervous system (CNS) metastases will be excluded (Pre-enrollment head CT is not required if not indicated by clinical signs or symptoms).
- Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis will be excluded.
- Subjects with serious concurrent chronic or acute illness such as pulmonary (asthma or COPD), cardiac (NYHA class III or IV) or hepatic disease, or other illness considered by the principal investigator to constitute an unwarranted high risk for investigational drug administration will be excluded.
- Subjects with medical or psychological impediment to probable compliance with the protocol will be excluded.
- Subjects with concurrent second malignancy other than melanoma or non-melanoma skin cancer will be excluded. In the event of prior non-melanoma malignancies treated surgically, the subject must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrollment.
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- Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology) will lead to subject exclusion.
- Subjects receiving steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression.
- Subjects with inadequate peripheral vein access to undergo leukapheresis will be excluded.
- Female subjects with a positive pregnancy test, as well as those who have not previously undergone hysterectomy and/or bilateral oophorectomy and are unwilling to utilize a medically approved form of contraception, from the time of enrollment until 6 weeks after the final immunization, will be excluded.
- Male subjects, not previously surgically sterilized, who are unwilling to use a condom with spermicide during any sexual activity occurring over the entire immunization period and for the 6 weeks that immediately follow the final immunization will be excluded.
- Subjects with a documented history of severe allergic reaction to beta-lactams, eggs or soy products.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Phase I Study of Active Immunotherapy of Metastatic Melanoma With Mature Autologous Dendritic Cells Transfected With Tumor Antigen RNA and Small Inhibitory RNAs to Alter Proteasomal Antigen Processing
Transfection with siRNA targeting the immunoproteasome alters proteasome-mediated antigen processing by the dendritic cell, generating TAA-derived peptides that we hypothesize, based on preclinical results, will induce enhanced anti-melanoma immune responses. This phase I study, open to subjects with metastatic melanoma, will assess the safety of vaccination with melanoma tumor associated antigen-encoding RNA-transfected mature dendritic cells derived from monocytes that have been either untreated, transfected with control siRNA, or transfected with siRNA targeting the inducible immunoproteasome beta subunits LMP2, LMP7, and MECL1. A combination of RNAs encoding melanoma tumor associated antigens MART-1, tyrosinase, gp100, and MAGE-3 will be utilized for dendritic cell transfection. The vaccine will be administered by intradermal injection in the extremities. Clinical and laboratory toxicities will be characterized for each study arm. As a secondary objective, this phase I study will also assess the anti-melanoma immune responses, as well as clinical responses, induced by vaccination with this dendritic cell-based product.
- Conditions
- Metastatic Melanoma, Absence of CNS Metastases
- Being tested
- Proteasome siRNA and tumor antigen RNA-transfected dendritic cells
- Keywords
- melanoma, dendritic cell, immunoproteasome, vaccine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proteasome siRNA and tumor antigen RNA-transfected dendritic cellsBiological
The safety and toxicity of vaccination with tumor antigen RNA-transfected dendritic cells (DC), derived from either untransfected or siRNA-transfected monocytes, will be evaluated in subjects with metastatic melanoma. Subjects will undergo leukapheresis and monocytes will be isolated. These monocytes will then be left untreated (Study Arm A) or transfected with either control siRNA (Study Arm B) or siRNA targeting immunoproteasome subunits LMP2, LMP7, and MECL1 (Study Arm C), then differentiated into DC in vitro . After the induction of maturation, these DC will be transfected with RNA encoding defined melanoma antigens MART, MAGE-3, tyrosinase, and gp100. These RNA-transfected autologous DC will be cryopreserved, then used to vaccinate subjects with metastatic melanoma, each of whom will receive a total of six intradermal (ID) injections using 1x10e7 DC at each cycle, administered weekly.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from untreated monocytes Receives: Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cells |
| B | Experimental | Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with control siRNA Receives: Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cells |
| C | Experimental | Vaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with siRNA targeting the three inducible immunoproteasome subunits Receives: Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
For this Phase I study, subjects will be evaluated both clinically and with laboratory testing for any signs of toxicity associated with vaccination.
Measured: 3 months after last vaccination
Secondary outcomes (2)
For each subject, the induction of anti-melanoma immune responses will be assessed by in vitro testing.
Measured: At least 3 months after final vaccination
For each subject, clinical responses to vaccination will also be assessed.
Measured: At least 3 months, and up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startJan 2008
- Primary completionMar 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scott Pruitt
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Scott Pruitt, Duke University
- Investigators
- Scott K Pruitt, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672542
- Sponsor's protocol ID
- Pro00000806
- Other IDs
- IND # BB-13545, NIH OBA # 0708-874
- Status last verified
- Jan 2014
- First submitted
- 3 Feb 2008
- Last updated
- 23 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Dannull J, Haley NR, Archer G, Nair S, Boczkowski D, Harper M, De Rosa N, Pickett N, Mosca PJ, Burchette J, Selim MA, Mitchell DA, Sampson J, Tyler DS, Pruitt SK. Melanoma immunotherapy using mature DCs expressing the constitutive proteasome. J Clin Invest. 2013 Jul;123(7):3135-45. doi: 10.1172/JCI67544. Epub 2013 Jun 24.
PubMed 23934126
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Active Immunotherapy of Metastatic Melanoma With Mature Autologous Dendritic Cells Transfected With Tumor Antigen RNA and Small Inhibitory RNAs to Alter Proteasomal Antigen Processing
- ClinicalTrials.gov ID
- NCT00672542
- Acronym / sponsor ID
- Pro00000806
- Conditions
- Metastatic Melanoma, Absence of CNS Metastases
- Keywords
- melanoma, dendritic cell, immunoproteasome, vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Scott PruittUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Mar 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 6 May 2008 (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.
Transfection with siRNA targeting the immunoproteasome alters proteasome-mediated antigen processing by the dendritic cell, generating TAA-derived peptides that we hypothesize, based on preclinical results, will induce enhanced anti-melanoma immune responses. This phase I study, open to subjects with metastatic melanoma, will assess the safety of vaccination with melanoma tumor associated antigen-encoding RNA-transfected mature dendritic cells derived from monocytes that have been either untreated, transfected with control siRNA, or transfected with siRNA targeting the inducible immunoproteasome beta subunits LMP2, LMP7, and MECL1. A combination of RNAs encoding melanoma tumor associated antigens MART-1, tyrosinase, gp100, and MAGE-3 will be utilized for dendritic cell transfection. The vaccine will be administered by intradermal injection in the extremities. Clinical and laboratory toxicities will be characterized for each study arm. As a secondary objective, this phase I study will also assess the anti-melanoma immune responses, as well as clinical responses, induced by vaccination with this dendritic cell-based product.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cellsVaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from untreated monocytes |
| B | Experimental | Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cellsVaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with control siRNA |
| C | Experimental | Biological: Proteasome siRNA and tumor antigen RNA-transfected dendritic cellsVaccination with melanoma tumor associated antigen RNA loaded dendritic cells derived from monocytes transfected with siRNA targeting the three inducible immunoproteasome subunits |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with confirmed metastatic melanoma.
- Karnofsky performance status greater than or equal to 70%.
- Estimated life expectancy > 6 months.
- Age > 18 years.
- Adequate hematologic function
Key exclusion criteria (12 listed)
- Subjects undergoing concurrent chemotherapy, radiation therapy, or immunotherapy will be excluded.
- The subject has previously irradiated, surgically treated, or newly diagnosed central nervous system (CNS) metastases will be excluded (Pre-enrollment head CT is not required if not indicated by clinical signs or symptoms).
- Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis will be excluded.
- Subjects with serious concurrent chronic or acute illness such as pulmonary (asthma or COPD), cardiac (NYHA class III or IV) or hepatic disease, or other illness considered by the principal investigator to constitute an unwarranted high risk for investigational drug administration will be excluded.
- Subjects with medical or psychological impediment to probable compliance with the protocol will be excluded.
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 |
|---|---|---|
| Proteasome siRNA and tumor antigen RNA-transfected dendritic cellsThe safety and toxicity of vaccination with tumor antigen RNA-transfected dendritic cells (DC), derived from either untransfected or siRNA-transfected monocytes, will be evaluated in subjects with metastatic melanoma. Subjects will undergo leukapheresis and monocytes will be isolated. These monocytes will then be left untreated (Study Arm A) or transfected with either control siRNA (Study Arm B) or siRNA targeting immunoproteasome subunits LMP2, LMP7, and MECL1 (Study Arm C), then differentiated into DC in vitro . After the induction of maturation, these DC will be transfected with RNA encoding defined melanoma antigens MART, MAGE-3, tyrosinase, and gp100. These RNA-transfected autologous DC will be cryopreserved, then used to vaccinate subjects with metastatic melanoma, each of whom will receive a total of six intradermal (ID) injections using 1x10e7 DC at each cycle, administered weekly. | Biological | A, B, C |
Primary outcome
For this Phase I study, subjects will be evaluated both clinically and with laboratory testing for any signs of toxicity associated with vaccination.
Time frame: 3 months after last vaccination
2 secondary outcomes
For each subject, the induction of anti-melanoma immune responses will be assessed by in vitro testing.
Time frame: At least 3 months after final vaccination
For each subject, clinical responses to vaccination will also be assessed.
Time frame: At least 3 months, and up to 5 years
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 23 Jan 2014.
- Results publication: PubMed 23934126Dannull J, Haley NR, Archer G, Nair S, Boczkowski D, Harper M, De Rosa N, Pickett N, Mosca PJ, Burchette J, Selim MA, Mitchell DA, Sampson J, Tyler DS, Pruitt SK. Melanoma immunotherapy using mature DCs expressing the constitutive proteasome. J Clin Invest. 2013 Jul;123(7):3135-45. doi: 10.1172/JCI67544. Epub 2013 Jun 24.
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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.
Scott K Pruitt, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Proteasome siRNA and tumor antigen RNA-transfected dendritic cells in people with Metastatic Melanoma and Absence of CNS Metastases, run by Scott Pruitt 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 12 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 23 Jan 2014. 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 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.
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?
For this Phase I study, subjects will be evaluated both clinically and with laboratory testing for any signs of toxicity associated with vaccination. (time frame: 3 months after last vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00672542, which also lists 1 linked publication.
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 23 Jan 2014.