Phase II Study of Metastatic Cancer That Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes and Dendritic Cell Vaccination
- Determine if the administration of anti-p53 T-cell receptor (TCR) gene-engineered
peripheral blood lymphocytes, high-dose aldesleukin, and adenovirus p53 dendritic cell
(DC) vaccine after a nonmyeloablative, but lymphoid-depleting, preparative regimen will
result in clinical tumor regression in patients with metastatic cancer that
- Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.
- Determine the ability of a dendritic cell (DC) vaccine to restimulate TCR
gene-engineered cells in vivo.
- Determine the toxicity profile of this treatment regimen.
OUTLINE: Patients are stratified according to type of metastatic cancer (melanoma or renal
cell cancer vs all other cancers).
- Peripheral blood mononuclear cell (PBMC) collection: Patients undergo PBMC collection
via leukapheresis for the generation of the adenovirus p53 dendritic cell vaccine as
well as anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes.
- Nonmyeloablative lymphocyte-depleting preparative regimen: Patients receive
cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine
phosphate IV over 30 minutes on days -5 to -1.
- Peripheral blood lymphocyte infusion: Patients receive anti-p53 TCR gene-engineered
peripheral blood lymphocytes IV over 20-30 minutes on day 0. Patients receive
filgrastim (growth colony stimulating factor (G-CSF)) subcutaneously (SC) once daily
beginning on day 1 or 2 and continuing until blood counts recover.
- High-dose aldesleukin: Patients receive high-dose aldesleukin IV over 15 minutes three
times daily on days 0-4 for up to 15 doses.
- Dendritic cell vaccine: Patients receive adenovirus p53 dendritic cell vaccine SC on
days 0, 7, 14, and 28.
Patients may receive one re-treatment course as above (nonmyeloablative preparative regimen,
peripheral blood lymphocyte infusion, high-dose aldesleukin, and dendritic cell
vaccinations) beginning 6-8 weeks after the last dose of high-dose aldesleukin.
After completion of study treatment, patients are followed periodically for up to 15 years.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical Response (Complete Response + Partial Response)
Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all lesions. Partial response is a 30% decrease in the sum of the longest diameter (LD) of target lesions.
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|