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
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.
- 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.
- Histologically proven recurrent, resected recurrent, or residual ovarian epithelial
- 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)
- 18 and over
- ECOG 0 or 1
- 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
- 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
- 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:
- More than 2 weeks since prior biologic therapy
- See Disease Characteristics
- More than 2 weeks since prior chemotherapy
- More than 2 weeks since prior endocrine therapy
- No concurrent steroids
- More than 2 weeks since prior radiotherapy
- See Disease Characteristics
- Prior debulking allowed