Human Telomerase Reverse Transcriptase Messenger RNA (hTERT mRNA) Transfected Dendritic Cell Vaccines
The purpose of this research is to develop a new and powerful type of immune therapy for prostate cancer patients. This therapy involves vaccinations with special stimulator cells found in the human body called dendritic cells. These dendritic cells can take up proteins released from cancer cells and present pieces of these proteins to immune cells called T lymphocytes to create a strong stimulatory signal to fight the cancer.
One of these proteins is called telomerase, which is found on prostate cancers and is critically important for prostate cancer cells to grow. However, in most cancer patients, the immune system does not adequately destroy the tumor because the T cells are not stimulated sufficiently. T cells require strong stimulation before they grow and become active against cancer cells.
We have discovered that substances called ribonucleic acids (RNA), which carry the genetic instructions for the production of telomerase, can be used to overcome this problem and stimulate a strong immune response in cancer patients.
In order to test this hypothesis we have designed a clinical study and will enroll patients with metastatic prostate cancer expressing telomerase in order to determine whether or not this vaccine will stimulate T cells, which can recognize and kill prostate tumor cells.
The main objectives of this study are to find out whether injections with dendritic cells grown from blood cells and "pulsed" (mixed together for a short period of time) with RNA derived from the patient's own tumor are:
- Safe without inducing any major side effects.
- And effective in boosting the patient body's immunity against telomerase expressing prostate cancer cells.
- Finally, we will test whether or not tumor shrinkage based on serum PSA levels or on X-ray studies will occur.
We hope that this new form of immune therapy, although in its infancy, will ultimately slow down tumor growth and prolong survival of prostate cancer patients.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Active Immunotherapy With Mature, Human Telomerase Reverse Transcriptase Messenger RNA -Transfected, Autologous Dendritic Cells (DC) Administered In A Prime-Boost Format to Subjects With Metastatic Prostate Cancer|
- The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC. [ Time Frame: 50 Weeks ] [ Designated as safety issue: Yes ]
All subjects will receive 1x107 cells administered ID at study weeks 1, 2, 3, 4, 5, and 6. Subjects will subsequently be randomized with equal probability to receive hTERT mRNA DC at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 at one of the following doses:
- 5x106 cells per infusion administered ID (Treatment arm A).
- 1x107 cells per infusion administered ID (Treatment arm B).
- PSA-specific T cells from pre- and post-therapy PBMC samples [ Time Frame: 50 Weeks ] [ Designated as safety issue: No ]To analyze the induction of PSA-specific T cells from pre- and post-therapy PBMC samples among subjects enrolled in both treatment arms.
- Calculate progression-free survival if subject responds to therapy. [ Time Frame: 50 Weeks ] [ Designated as safety issue: No ]To monitor eventual clinical responses as evidenced on clinical response criteria and calculate progression-free survival if subject responds to therapy.
- overall survival [ Time Frame: 50 Weeks ] [ Designated as safety issue: No ]To determine overall survival for all subjects at one-year of follow-up.
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||December 2010|
|Estimated Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Experimental: Treatment Arm A
• 5x106 cells per infusion administered ID
Biological: hTERT mRNA DC
Subjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 5x106 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50.
Experimental: Treatment Arm B
• 1x107 cells per infusion administered ID (Treatment arm B).
Biological: hTERT mRNA DC
Subjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 1x107 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50.
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