Intraocular MelanomaPhase 1NCT00313508
Dendritic Cell Vaccination During Lymphoid Reconstruction
A Phase 1 study testing Autologous Dendritic Cells (DC), Fludarabine and Autologous Lymphocyte Infusion (ALI) in people with Intraocular Melanoma and Melanoma (Skin), run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms. The purpose of this study is to find out what side effects are caused in this study and whether Fludarabine with the dendritic cell vaccine (DC vaccine) can increase the ability of the… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Intraocular Melanoma, Melanoma (Skin)
- What is being tested?
- Autologous Dendritic Cells (DC), Fludarabine and Autologous Lymphocyte Infusion (ALI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Mar 2012
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Metastatic melanoma with measurable disease after attempted curative surgical therapy and without prior chemotherapy; adjuvant interferon or isolated limb perfusion is allowed.
- Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1/tyrosinase/NY-ESO-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement.
- Patients must be HLA-A *0201 positive by a DNA polymerase chain reaction (PCR) analysis.
- Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and alanine transaminase/aspartic transaminase (ALT/AST) of less than 3X institutional upper limit of normal (ULN).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Patients must be able to understand and sign an Institutional Review Board (IRB) approved informed consent form.
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- Patients must have whit blood count (WBC) of 3000 or greater, platelets of 100,000 or greater, and hemoglobin of 9.0 gm/dl or more.
- Patients must be seropositive for Epstein-Barr virus (EBV).
- Patients with unresectable stages III/IV uveal melanoma and metastatic mucosal melanoma will be eligible for this trial.
Who cannot join
- Patients who are undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy.
- Have major systemic infections, coagulation disorders, or other major medical illnesses (MI) of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months.
- Require steroid therapy.
- Are pregnant or lactating.
- Are known to be positive for hepatitis BsAg, Hepatitis C or human immunodeficiency virus (HIV) antibody, since cells for DC cannot be grown in the laboratory when virus contaminated.
- Have a prior history of uveitis or autoimmune inflammatory eye disease.
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- Have previously received the gp100 209-217 (210M), MART-1 26-35 (27L), gp100 280-288 (288V), tyrosinase 207-215 or NY-ESO-1 157-165 (165V) peptides.
- Have had another malignancy other than cervical carcinoma-in-situ or basal cell
- /squamous cancer of the skin, unless they have undergone curative therapy more than 5 years ago and are still free of detectable disease.
- Since this trial increase the risk of immunological impairment, patients with the following will be excluded from this trial: Hypogammaglobulinemia, Lymphocytopenia, History of impaired immune response, tuberculosis (TB) or positive purified protein derivative (PPD) unless they have received BCG vaccine.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612-9497
About this study
Official title: A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines With Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma
This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms.
The purpose of this study is to find out what side effects are caused in this study and whether Fludarabine with the dendritic cell vaccine (DC vaccine) can increase the ability of the immune system to recognize melanoma.
Read the detailed description
This is a dose ranging study of intranodal administration of autologous dendritic cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100 (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215 as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of Fludarabine. The nine or ten amino acid peptides representing HLA-A2 restricted T cell epitopes of MART-1, gp100, NY-ESO-1 and tyrosinase will be pulsed onto autologous dendritic cells produced by incubation of peripheral blood mononuclear cells obtained by apheresis with interleukin-4 (IL-4) and GM-CSF and pulsed with four helper peptides then matured with a cytokine cocktail including TNF-a, IL-6, IL-1b and PGE2. Melanoma antigen peptide-pulsed dendritic cells will be administered at a total dose of 10 million cells each for four intranodal injections to patients with chemotherapy-naïve metastatic melanoma.
DC matured with a cytokine cocktail and pulsed with class I and II peptides will be injected intranodally, weekly for two doses, then every two weeks for two doses, for a total of four injections to each cohort.
- Conditions
- Intraocular Melanoma, Melanoma (Skin)
- Being tested
- Autologous Dendritic Cells (DC), Fludarabine, Autologous Lymphocyte Infusion (ALI)
- Keywords
- stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, recurrent intraocular melanoma, metastatic intraocular melanoma, extraocular extension melanoma, iris melanoma
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Dendritic Cells (DC)Biological
Also called Autologous Dendritic Cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100, (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215, as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase, (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of
Given intranodally
FludarabineDrug
Also called fludarabine phosphate, FLUDARA
Fludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days.
Autologous Lymphocyte Infusion (ALI)Biological
Also called ALI
Infusion
| Study group | Role | What they receive |
|---|---|---|
| A: Peptide-pulsed DC, ALI and Low Dose Fludarabine | Experimental | Fludarabine: 5 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion Receives: Biological: Autologous Dendritic Cells (DC); Drug: Fludarabine; Biological: Autologous Lymphocyte Infusion (ALI) |
| B: Peptide-pulsed DC, ALI and High Dose Fludarabine | Experimental | Fludarabine: 25 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion Receives: Biological: Autologous Dendritic Cells (DC); Drug: Fludarabine; Biological: Autologous Lymphocyte Infusion (ALI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall Survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up.
Measured: 3 years, 6 months
Secondary outcomes (2)
Progression-Free Survival (PFS)
Progression-Free Survival is defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Evaluation of target lesions: Progressive Disease (PD)- At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: 3 years, 6 months
Time to Progression (TTP)
Time to Progression is defined as the time from first day of treatment to the first observation of disease progression or death due to disease. If failure has not occurred, failure time is censored at the time of last follow-up. Evaluation of target lesions: Progressive Disease (PD)- At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measured: 3 years, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2006 (estimated)
- Study startFeb 2006
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intraocular 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jeffrey S. Weber, M.D., Ph.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00313508
- Sponsor's protocol ID
- MCC-13649
- Other IDs
- NCI-6241
- Status last verified
- Dec 2012
- First submitted
- 11 Apr 2006
- Last updated
- 21 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines With Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00313508
- Acronym / sponsor ID
- MCC-13649
- Conditions
- Intraocular Melanoma, Melanoma (Skin)
- Keywords
- stage IV melanoma, recurrent melanoma, ciliary body and choroid melanoma, medium/large size, recurrent intraocular melanoma, metastatic intraocular melanoma, extraocular extension melanoma, iris melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2006
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 12 Apr 2006 (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.
This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms.
The purpose of this study is to find out what side effects are caused in this study and whether Fludarabine with the dendritic cell vaccine (DC vaccine) can increase the ability of the immune system to recognize melanoma.
Detailed description
This is a dose ranging study of intranodal administration of autologous dendritic cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100 (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215 as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses of Fludarabine. The nine or ten amino acid peptides representing HLA-A2 restricted T cell epitopes of MART-1, gp100, NY-ESO-1 and tyrosinase will be pulsed onto autologous dendritic cells produced by incubation of peripheral blood mononuclear cells obtained by apheresis with interleukin-4 (IL-4) and GM-CSF and pulsed with four helper peptides then matured with a cytokine cocktail including TNF-a, IL-6, IL-1b and PGE2. Melanoma antigen peptide-pulsed dendritic cells will be administered at a total dose of 10 million cells each for four intranodal injections to patients with chemotherapy-naïve metastatic melanoma.
DC matured with a cytokine cocktail and pulsed with class I and II peptides will be injected intranodally, weekly for two doses, then every two weeks for two doses, for a total of four injections to each cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Peptide-pulsed DC, ALI and Low Dose Fludarabine | Experimental | Biological: Autologous Dendritic Cells (DC), Drug: Fludarabine, Biological: Autologous Lymphocyte Infusion (ALI)Fludarabine: 5 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion |
| B: Peptide-pulsed DC, ALI and High Dose Fludarabine | Experimental | Biological: Autologous Dendritic Cells (DC), Drug: Fludarabine, Biological: Autologous Lymphocyte Infusion (ALI)Fludarabine: 25 mg/m^2/day, Auto Lymphocyte Infusion, DC Infusion |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Metastatic melanoma with measurable disease after attempted curative surgical therapy and without prior chemotherapy; adjuvant interferon or isolated limb perfusion is allowed.
- Tumor tissue must be available for immunohistochemical analysis, and specimens will stained for MART-1/tyrosinase/NY-ESO-1 by immunohistochemical staining and will also be stained for HMB-45 by immunohistochemistry, and positivity for at least one will be an entry requirement.
- Patients must be HLA-A *0201 positive by a DNA polymerase chain reaction (PCR) analysis.
- Serum creatinine of 2.0 mg/dl or less, total bilirubin of 2.0 mg/dl or less, and alanine transaminase/aspartic transaminase (ALT/AST) of less than 3X institutional upper limit of normal (ULN).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (10 listed)
- Patients who are undergoing or have undergone in the past month any other therapy for their melanoma, including radiation therapy, chemotherapy and adjuvant therapy.
- Have major systemic infections, coagulation disorders, or other major medical illnesses (MI) of the cardiovascular or respiratory systems, or have had a documented MI in the last 6 months.
- Require steroid therapy.
- Are pregnant or lactating.
- Are known to be positive for hepatitis BsAg, Hepatitis C or human immunodeficiency virus (HIV) antibody, since cells for DC cannot be grown in the laboratory when virus contaminated.
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 |
|---|---|---|
| Autologous Dendritic Cells (DC)Also: Autologous Dendritic Cells (DC) pulsed with tumor antigen class I peptides derived from MART-1 (26-35) (27L), gp100, (209-217 (210M), gp100 280-288 (288V), NY-ESO-1 157-165 (165V) and tyrosinase 207-215, as well as class II MART-1 (51-73), NY-ESO-1 (119-143), MAGE-3 (243-258) and tyrosinase, (450-462) peptides preceded by Autologous Lymphocyte Infusion (ALI) and one of two doses ofGiven intranodally | Biological | A: Peptide-pulsed DC, ALI and Low Dose Fludarabine, B: Peptide-pulsed DC, ALI and High Dose Fludarabine |
| FludarabineAlso: fludarabine phosphate, FLUDARAFludarabine will be administered intravenously (IV) over 30 minutes, daily for 5 consecutive days. | Drug | A: Peptide-pulsed DC, ALI and Low Dose Fludarabine, B: Peptide-pulsed DC, ALI and High Dose Fludarabine |
| Autologous Lymphocyte Infusion (ALI)Also: ALIInfusion | Biological | A: Peptide-pulsed DC, ALI and Low Dose Fludarabine, B: Peptide-pulsed DC, ALI and High Dose Fludarabine |
Primary outcome
Overall Survival (OS)
Time frame: 3 years, 6 months
Overall Survival is defined as the time from first day of treatment to time of death due to any cause. If a patient is still alive, survival time is censored at the time of last follow-up.
2 secondary outcomes
Progression-Free Survival (PFS)
Time frame: 3 years, 6 months
Time to Progression (TTP)
Time frame: 3 years, 6 months
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 21 Feb 2014.
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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.
Jeffrey S. Weber, M.D., Ph.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 Autologous Dendritic Cells (DC), Fludarabine and Autologous Lymphocyte Infusion (ALI) in people with Intraocular Melanoma and Melanoma (Skin), run by H. Lee Moffitt Cancer Center and Research Institute 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 9 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 21 Feb 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?
Overall Survival (OS) (time frame: 3 years, 6 months). 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 21 Feb 2014.