Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI NCI-96-C-0011 NCI-T95-0040N, T95-0040, NCT00019136

Objectives

1. 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).
2. Evaluate the ability of intravenously administered MOv-PBL to traffic to sites of ovarian cancer.
3. Determine the duration of survival of transduced lymphocytes in the systemic circulation and at the tumor site in these patients.

Entry 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)

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0 or 1

Hematopoietic:

• WBC greater than 3,000/mm³
• Platelet count greater than 100,000/mm³
• 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:

• FEV₁ 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

Expected Enrollment

Approximately 13-50 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Steven Rosenberg, MD, PhD, Protocol chair		Ph: 301-496-4164 Email: sar@nih.gov

Registry Information
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
Trial Start Date		1997-02-28
Registered in ClinicalTrials.gov		NCT00019136
Date Submitted to PDQ		1995-11-07
Information Last Verified		2003-12-08