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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019136
First received: July 11, 2001
Last updated: February 6, 2009
Last verified: December 2003
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Biological: MOv-gamma chimeric receptor gene
Biological: aldesleukin
Biological: therapeutic allogeneic lymphocytes
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: February 1997
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019136

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00019136     History of Changes
Obsolete Identifiers: NCT00001494
Other Study ID Numbers: CDR0000064488, NCI-96-C-0011, NCI-T95-0040N
Study First Received: July 11, 2001
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent ovarian epithelial cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Aldesleukin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 20, 2014