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

April 28, 2015 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 1997

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 29, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

December 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000064488
  • NCI-96-C-0011
  • NCI-T95-0040N

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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