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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Ovarian Cancer

Treatments: Biological: MOv-gamma chimeric receptor gene; Biological: aldesleukin; Biological: therapeutic allogeneic lymphocytes

Study type: Interventional

Funder types: NIH

Identifiers

NCT00019136

NCI-T95-0040N

NCI-96-C-0011

CDR0000064488

Details and patient eligibility

About

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.

Full description

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.

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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