gene therapy and biological therapy in treating patients with ovarian epithelial cancer

Conditions: Ovarian Cancer

Summary: rationale: interleukin-2 may stimulate a person's white blood cells to kill ovarian cancer cells. interleukin-2 combined with white blood cells that are gene-modified to recognize and kill ovarian cancer cells may be an effective treatment for recurrent or residual ovarian cancer. purpose: phase i trial to study the effectiveness of interleukin-2 plus gene-modified white blood cells in treating patients who have advanced ovarian epithelial cancer.

objectives: * 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 ovarian cancer. * 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.

Eligibility criteria:
disease characteristics: * histologically proven recurrent, resected recurrent, or residual ovarian epithelial cancer * failed prior standard effective therapy including cisplatin/carboplatin or paclitaxel * tumor positive for folate-binding protein by monoclonal antibody mov18 binding * measurable disease by ct scan, mri, ultrasound, or physical exam or * minimal residual disease on laparotomy, laparoscopy, or peritoneal washings (i.e., disease not evaluable radiologically or on physical exam) patient characteristics: age: * 18 and over performance status: * ecog 0 or 1 hematopoietic: * wbc greater than 3,000/mm\^3 * platelet count greater than 100,000/mm\^3 * hemoglobin greater than 9.0 g/dl * no coagulation disorder hepatic: * bilirubin no greater than 2.0 mg/dl * other liver function tests less than 3 times upper limit of normal * hepatitis b antigen negative renal: * creatinine no greater than 2.0 mg/dl cardiovascular: * no major cardiovascular illness * if history of ischemic heart disease, congestive heart failure, or cardiac arrhythmias, not eligible to receive interleukin-2 pulmonary: * fev_1 and dlco greater than 70% predicted * no major respiratory illness immunologic: * must have an intact immune system as evidenced by a positive reaction to candida albicans, mumps, or tetanus toxoid skin tests on a standard anergy panel * hiv negative * no active systemic infection other: * not pregnant * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * more than 2 weeks since prior biologic therapy chemotherapy: * see disease characteristics * more than 2 weeks since prior chemotherapy endocrine therapy: * more than 2 weeks since prior endocrine therapy * no concurrent steroids radiotherapy: * more than 2 weeks since prior radiotherapy surgery: * see disease characteristics * prior debulking allowed

Keywords: recurrent ovarian epithelial cancer