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

NCT ID: NCT00019136

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-02-28

Brief 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.

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.

Conditions

Ovarian Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

MOv-gamma chimeric receptor gene

Intervention Type: BIOLOGICAL

aldesleukin

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Steven A. Rosenberg, MD, PhD

Role: STUDY_CHAIR

NCI - Surgery Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Countries

United States

References

Pinte L, Cunningham A, Trebeden-Negre H, Nikiforow S, Ritz J. Global Perspective on the Development of Genetically Modified Immune Cells for Cancer Therapy. Front Immunol. 2021 Feb 15;11:608485. doi: 10.3389/fimmu.2020.608485. eCollection 2020.

Reference Type: DERIVED

PMID: 33658994 (View on PubMed)

Other Identifiers

NCI-96-C-0011

Identifier Type: -

Identifier Source: secondary_id

NCI-T95-0040N

Identifier Type: -

Identifier Source: secondary_id

CDR0000064488

Identifier Type: -

Identifier Source: org_study_id

NCT00001494

Identifier Type: -

Identifier Source: nct_alias