cellular adoptive immunotherapy in treating patients with stage iii or stage iv ovarian cancer or primary peritoneal cancer

Conditions: Ovarian Cancer; Peritoneal Cavity Cancer

Summary: rationale: biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop tumor cells from growing. purpose: this phase i trial is studying the side effects and best dose of cellular adoptive immunotherapy in treating patients with stage iii or stage iv ovarian cancer or primary peritoneal cancer.

objectives: primary * determine the safety and toxicity of autologous cd4-positive antigen-specific t cells in patients with stage iii or iv ovarian epithelial cancer or primary peritoneal cavity cancer. * determine the duration of in vivo persistence of this drug in these patients. secondary * determine the antitumor effect of this drug in these patients. outline: this is a dose-escalation study. patients undergo leukapheresis for collection of t cells. responder t cells are stimulated in vitro with autologous peripheral blood mononuclear cell-derived dendritic cells pulsed with ny-eso-1 immunogenic peptides. patients receive autologous cd4-positive antigen-specific t cells iv over 30 minutes. cohorts of 3-6 patients receive escalating doses of autologous cd4-positive antigen-specific t cells until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed at 4, 8, and 12 weeks and then periodically thereafter for survival. projected accrual: a total of 9-18 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed stage iii or iv ovarian epithelial cancer or primary peritoneal cavity cancer meeting 1 of the following criteria: * progressive\* or persistent\* disease during or after primary chemotherapy * recurrent disease \< 6 months after completion of primary therapy that had resulted in a complete response * persistent\* or recurrent disease after second-line or additional therapies note: \*progression or persistence can be based on serological (ca 125 \> 100 u/ml or 2 times baseline), radiographic (measurable or evaluable disease), or second-look surgical findings * tumor expressing ny-eso-1 determined by ihc or rt-pcr * hla type expressing dpb\*0401, dpb1\*0201, drb1\*07 * no cns metastases patient characteristics: age * 18 to 75 performance status * karnofsky 70-100% life expectancy * more than 16 weeks hematopoietic * not specified hepatic * not specified renal * creatinine ≤ 2.0 mg/dl cardiovascular * no congestive heart failure\* * no clinically significant hypotension\* * no symptoms of coronary artery disease\* * no cardiac arrhythmias on ekg requiring drug therapy\* * no history of cardiovascular disease\* * no other significant cardiovascular abnormalities\* note: \*patients with any of the above undergo a stress test and/or echocardiography before being determined ineligible for study participation pulmonary * fev_1 ≥ 60% of predicted\* * dlco ≥ 55%\* note: \*patients with clinically significant pulmonary dysfunction only other * not pregnant or nursing * fertile patients must use effective contraception * hiv negative * no active infection * no oral temperature \> 38.2°c within the past 72 hours * no systemic infection requiring chronic maintenance or suppressive therapy prior concurrent therapy: biologic therapy * no other concurrent immunotherapy (e.g., interleukins, interferons, vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy) chemotherapy * see disease characteristics * at least 3 weeks since prior standard or experimental chemotherapy endocrine therapy * no concurrent systemic corticosteroids except for treatment-related toxicity radiotherapy * at least 3 weeks since prior radiotherapy surgery * see disease characteristics other * at least 3 weeks since prior immunosuppressive therapy * more than 3 weeks since prior investigational drugs and recovered * no other concurrent investigational agents * no concurrent pentoxifylline

Keywords: recurrent ovarian epithelial cancer stage iii ovarian epithelial cancer stage iv ovarian epithelial cancer peritoneal cavity cancer