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Activation of pDCs at the Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Melanoma

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Trial Information

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.


Inclusion Criteria:



1. HLA-A*0201 positive (to enable immunization with the HLA class I restricted
gp100(g209-2M) peptide).

2. HLA-DP4 positive (to enable immunization with the HLA class II restricted MAGE-3
peptide).

3. Patients >/= 18 years old with histologically documented metastatic melanoma with
measurable disease, stage IIIC (in transit lesions) or stage IV M1A with disease that
includes lesions accessible for biopsies.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. At least 4 biopsiable cutaneous lesions

6. White Blood Count (WBC) >/= 3000/mm^3 (part 1 & 2)

7. Platelet count >/= 90,000/mm^3 (part 1 & 2)

8. Serum alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) upper limit of normal (ULN) (part 1 & 2)

9. Total bilirubin have a total bilirubin less than 3.0 mg/dl Total bilirubin for patients with Gilbert's syndrome who must have a total bilirubin less than 3.0
mg/dl (part 1 & 2)

10. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental
treatment being evaluated in this protocol depends on an intact immune system.
Patients who are HIV seropositive can have decreased immune competence and thus may
be less responsive to the experimental treatment and more susceptible to its
toxicities.)

11. Negative pregnancy test for women of childbearing potential (WOCBP) A WOCBP has not
undergone a hysterectomy or who has not been naturally postmenopausal for at least 12
consecutive months (i.e., who has had menses at any time in the preceding 12
consecutive months)

12. Patients of both gender must practice a barrier method of birth control while
participating in this trial.

Exclusion Criteria:

1. Autoimmune disease

2. Concurrent systemic or inhaled steroid therapy

3. Any form of active primary or secondary immunodeficiency

4. Prior malignancy except for the following: adequately treated basal cell or squamous
cell skin cancer, in-situ cervical cancer, or any cancer from which the patient has
been disease-free for 5 years

5. History of immunization with gp100(g209-2M) or MAGE-3

6. Active systemic infections requiring intravenous antibiotics

7. Women who are breastfeeding

8. Prior systemic therapy, radiation therapy or surgery within 28 days of starting study
treatment

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of Immune Responses of Vaccine+R848 to Vaccine Alone

Outcome Description:

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.

Outcome Time Frame:

8 weeks

Safety Issue:

No

Principal Investigator

Richard Royal, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2008-0416

NCT ID:

NCT00960752

Start Date:

May 2010

Completion Date:

Related Keywords:

  • Melanoma
  • gp100 peptide
  • MAGE-3 peptide
  • R848
  • Resiquimod
  • Toll Like Receptor
  • TLR
  • T-cells
  • Tumor
  • Metastatic
  • Lesions
  • Injection Site
  • Melanoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030