Activation of pDCs at the Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist
The Study Drug/Vaccines:
Resiquimod (R848) is designed to increase the production of antigen-specific T-cells, to
activate immune cells, and to increase T-cells going into the tumor, which may cause the
tumor cells to die.
gp100 and MAGE-3 are vaccines designed to stimulate immune cells, also called T-cells, which
may help the immune system to recognize and kill melanoma cells.
Study Groups:
- If you are found to be eligible to take part in this study, you will be randomly
assigned (as in the flip of a coin) to 1 of 2 groups.
- If you are in Group 1, you will receive the vaccines (gp100 and MAGE-3) and R848 for 8
weeks. After 8 weeks, you will apply R848 to half of the lesions on your body for 16
weeks.
- If you are in Group 2, you will receive the vaccines (gp100 and MAGE-3) only for 8
weeks. After 8 weeks, you will apply R848 to half of the lesions on your body for 16
weeks.
Study Drug/Vaccine Administration:
Once a week for 8 weeks, you will receive the vaccines, gp100 and MAGE-3, intradermally
(through a needle into your skin) and subcutaneously (through a needle under your skin) at 2
separate sites. Half of each dose will be given one way, and half given the other way.
These vaccines will also be given on the same day.
If you are in Group 1, every time you have the vaccine injection, R848 will be applied as a
gel over the gp100 injection site. The R848 gel will be allowed to air dry for 30 minutes
and then covered with a gauze dressing.
After 8 weeks, 2 times a week for 16 weeks, both groups will apply the R848 gel to half of
the lesions on their body. You will be given written instructions and a "hands-on"
demonstration on how to apply the gel. You will also be given a worksheet to help you with
applying the gel.
Study Visits:
At Week 2, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine
combinations.
Every 4 weeks, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine
combinations.
Every 8 weeks, the following tests and procedures will be performed:
- You will have CT scans of the chest, abdomen, and pelvis to check the status of the
disease.
- The tumors will be measured and photographed. Your private areas will be covered (as
much as possible), and a picture of your face will not be taken unless there are tumors
on your face.
- If the doctor thinks it is necessary, the tumors will be measured by CT scan.
- You will have an MRI/CT of the brain to check the status of the disease.
At Week 0 (before vaccine is started) and Week 16, white blood cells will be collected by
leukapheresis. The leukapheresis procedure is research-related and would not be performed as
standard of care if you were not on study. Blood for the leukapheresis will be taken through
a needle in a vein 1 of your arms. A solution will be added to keep your blood from
clotting while it goes through the machine that collects and removes white blood cells from
your blood. The remaining blood is returned to you through a needle in a vein of your other
arm. This is may take up to 3-4 hours. Although several pints of blood will go through the
machine, only about 1/2 a pint (1 cup) will be in the machine at any time. If you cannot
have a needle in your vein, this blood will be removed thorough a central venous catheter
(CVC). A CVC is a sterile flexible tube that will be placed into a large vein while you are
under local anesthesia. You will be given another informed consent document to sign, which
describes the risks of the CVC and the care involved.
Length of Study:
You will continue to receive treatment for up to 4 months, as long as you may benefit from
the study and are responding to the gel. You will be taken off study if the disease gets
worse or you experience any intolerable side effects.
This is an investigational study. The study drugs/vaccines gp100, MAGE-3, and R848 are not
FDA approved or commercially available. At this time, they are only being used in research.
Up to 48 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Comparison of Immune Responses of Vaccine+R848 to Vaccine Alone
T-cell response to gp100(g209-2M) +/- MAGE3 measured at 8 weeks using a tetramer/multimer assay measured by flow cytometry. Based on the number of gp100(g209-2M) +/- MAGE3 T-cells measured, categorized as either immune responders or immune non-responders. T-cell response to the gp100(g209-2M) + /- MAGE3 peptide in each participant defined as ≥0.1% gp100(g209-2M) tetramer+ cells in the CD8+ T-cell population or ≥0.1% MAGE3 multimer cells in the CD4+ T-cell population.
8 weeks
No
Richard Royal, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2008-0416
NCT00960752
May 2010
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |