Gene Therapy and Biological Therapy in Treating Patients With Ovarian Epithelial Cancer

Phase 1CompletedNCT00019136

National Cancer Institute (NCI)

Overview

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Ovarian Cancer

Interventions

MOv-gamma chimeric receptor geneBIOLOGICAL

aldesleukinBIOLOGICAL

therapeutic allogeneic lymphocytesBIOLOGICAL

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Data from ClinicalTrials.gov

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