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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •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
- •Bilirubin no greater than 2.0 mg/dL
- •Other liver function tests less than 3 times upper limit of normal
- •Hepatitis B antigen negative
- •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
- •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
- •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
- •See Disease Characteristics
- •Prior debulking allowed
排除标准
- 未提供