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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00019136
• Other study ID #: CDR0000064488
• Secondary ID: NCI-96-C-0011NCI
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: April 28, 2015
• Start date: February 1997

Study information

• Verified date: December 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00001494

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Biological:
• MOv-gamma chimeric receptor gene

• aldesleukin

• therapeutic allogeneic lymphocytes

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,