Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer
RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to the cancer cells. Vaccines made from a gene-modified virus and a person's white blood cells may help the body build an effective immune response to kill cancer cells. Giving denileukin diftitox together with vaccine therapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects of giving denileukin diftitox together with vaccine therapy in treating patients with metastatic cancer that expresses carcinoembryonic antigen.
Unspecified Adult Solid Tumor, Protocol Specific
Biological: denileukin diftitox
Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine
Biological: therapeutic autologous dendritic cells
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Regulatory T Cell Depletion With Denileukin Diftitox Followed by Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox-Tricom in Patients With Advanced or Metastatic Malignancies Expressing CEA|
- Safety as measured by rate of adverse events during study drug treatment [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Rate of immune response as measured by ELISPot at week 10 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||May 2009|
|Primary Completion Date:||March 2007 (Final data collection date for primary outcome measure)|
Experimental: Denileukin Diftitox plus vaccine
This is a single arm Phase I safety study.
|Biological: denileukin diftitox Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine Biological: therapeutic autologous dendritic cells|
- Determine the safety and feasibility of two different schedules of denileukin diftitox followed by active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA(6D)-TRICOM vaccine in patients with metastatic CEA-expressing malignancies.
- Determine the immune response to this regimen in these patients.
- Determine, preliminarily, clinical response rate and/or time to progression in patients with assessable disease treated with this regimen.
OUTLINE: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are cultured with sargramostim (GM-CSF) and interleukin-4 for the production of dendritic cells( DC). DC are mixed with recombinant fowlpox-TRICOM to produce the vaccine. Patients are assigned to 1 of 2 cohorts according to timing of study enrollment.
- Cohort 1: Patients receive denileukin diftitox IV over at least 15 minutes once in week 0 and vaccine therapy comprising autologous DC infected with recombinant fowlpox-CEA (6D)-TRICOM vaccine intradermally and subcutaneously once in weeks 0 (beginning 4 days after the denileukin diftitox infusion), 3, 6, and 9. If < 2 of 6 patients experience dose-limiting toxicity, a second cohort of patients is enrolled.
- Cohort 2: Patients receive denileukin diftitox as in cohort 1 once in weeks 0, 3, 6, and 9 and vaccine as in cohort 1.
In both cohorts, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed annually for up to 15 years.
PROJECTED ACCRUAL: A total of 6-12 patients (6 per cohort) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00128622
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Study Chair:||Michael A. Morse, MD||Duke Cancer Institute|