TREATMENT OF PATIENTS WITH ADVANCED EPITHELIAL OVARIAN CANCER USING ANTI-CD3 STIMULATED PERIPHERAL BLOOD LYMPHOCYTES TRANSDUCED WITH A GENE ENCODING A CHIMERIC T-CELL RECEPTOR REACTIVE WITH FOLATE BINDING PROTEIN
- Determine the clinical response in patients with advanced ovarian epithelial cancer
treated with intravenously administered allogeneic peripheral blood mononuclear
cell-stimulated, gene-modified lymphocytes (MOv-PBL).
- Evaluate the ability of intravenously administered MOv-PBL to traffic to sites of
- Determine the duration of survival of transduced lymphocytes in the systemic
circulation and at the tumor site in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified by eligibility to receive
interleukin-2 (IL-2) (yes vs no).
Patients undergo leukapheresis. The collected peripheral blood lymphocytes (PBLs) are
stimulated with allogeneic peripheral blood mononuclear cells (PBMCs) followed by retroviral
transduction with antiovarian cancer MOv-gamma chimeric receptor gene (MOv-PBL). MOv-PBL are
then reinfused IV over 30-60 minutes followed by IL-2 IV over 15-30 minutes every 12 hours
for up to 8 doses (if eligible). This course may be repeated at least once, beginning 2-3
weeks later. Patients receiving allogeneic PBMC-stimulated PBLs receive donor PBMCs
subcutaneously at 1 and 8 days after each MOv-PBL infusion instead of IL-2.
Cohorts of 3-6 patients in each stratum receive escalating doses of MOv-PBL until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients receive
MOv-PBL, without IL-2, followed by immunization with donor PBMCs as above.
Patients are followed at 4 and 8 weeks and then periodically for survival.
PROJECTED ACCRUAL: Approximately 13-50 patients will be accrued for this study.
Primary Purpose: Treatment
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|