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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


Phase 1
18 Years
N/A
Not Enrolling
Female
Ovarian Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Surgery Branch

Authority:

United States: Federal Government

Study ID:

CDR0000064488

NCT ID:

NCT00019136

Start Date:

February 1997

Completion Date:

Related Keywords:

  • Ovarian Cancer
  • recurrent ovarian epithelial cancer
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182