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White Blood Cells With Anti-EGFR-III for Malignant Gliomas

2014-12-03 09:44:50 | BioPortfolio

Summary

Background:

- A new cancer treatment involves collecting white blood cells from a patient, modifying them to act against the cancer, and returning them to the body. The white blood cells may then be able to identify and destroy the cancer cells. Some kinds of advanced gliomas contain a protein called EGFR, which is not present in normal tissues. Doctors want to modify white blood cells to have an anti-EGFR effect, and use them to treat the glioma.

Objectives:

- To see if anti-EGFR white blood cells are a safe and effective treatment for advanced gliomas.

Eligibility:

- Individuals greater than or equal to 18 years of age and less than or equal to 66 years of age who have a malignant glioma that has not responded to standard treatments.

Design:

- Participants will be screened with a medical history and physical exam. They will also have blood tests and imaging studies.

- Participants will have leukapheresis about a month before the treatment to collect white blood cells.

- They will have chemotherapy 1 week before the treatment to prepare the body for the anti-EGFR cells.

- The anti-EGFR cells will be given as an infusion. Interleukin-2 will be given along with the cells to help boost the immune system s response. It will be given every 8 hours for up to 15 doses.

- Participants will be monitored in the hospital with blood tests and other studies during their recovery from treatment.

- Participants will have regular followup exams with blood tests, imaging studies, and other exams every 1 to 6 months.

Description

BACKGROUND:

- Patients with recurrent gliomas have very limited treatment options. EGFR variant III

(EGFRvIII) is the most common mutant variant of EGFR and is present in 24-67% of patients with glioblastoma.

- EGFRvIII expression promotes oncogenesis and is associated with poor prognosis.

- EGFRvIII is not expressed in normal tissue and is an attractive target for immunotherapy.

- We have constructed a retroviral vector that contains a chimeric antigen receptor (CAR) that recognizes the EGFRvIII tumor antigen, which can be used to mediate genetic transfer of this CAR with high efficiency without the need to perform any selection.

OBJECTIVES:

Primary Objectives

- To evaluate the safety of the administration of anti-EGFRvIII CAR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative conditioning regimen, and aldesleukin

- Determine the six month progression free survival of patients receiving anti-EGFRvIII CAR-engineered peripheral blood lymphocytes and aldesleukin following a nonmyeloablative but lymphoid depleting preparative regimen.

Secondary objectives

- Determine the in vivo survival of CAR gene-engineered cells.

- Evaluate radiographic changes after treatment

ELIGIBILITY:

- Histologically proven glioblastoma or glisarcoma expressing EGFRvIII as determined by IHC or RT-PCR

- Failed prior standard treatment with radiotherapy with or without chemotherapy

- Karnofsky score greater than or equal to 60%

- Cardiac, pulmonary and laboratory parameters within acceptable limits

DESIGN:

- The study will be conducted using a Phase I/II design.

- Patients will receive a non-myeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, CAR gene-transduced PBMC, plus IV aldesleukin.

- Once the MTD has been determined, the study will proceed to the phase II portion.

- In the phase 2 portion of the trial, patients will be accrued to two groups:

- Patients with recurrent malignant glioma requiring steroid use at the start of treatment

- Patients with recurrent malignant glioma not requiring steroids at the start of treatment

- A total of 160 patients may be enrolled over a period of 7 years.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Malignant Glioma

Intervention

Anti-EGFRvIII CAR transduced PBL, Aldesleukin, Fludarabine, Cyclophosphamide

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-12-03T09:44:50-0500

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