A Phase I/II Study of the Safety and Feasibility of Administering T Cells Expressing Anti-EGFRvIII Chimeric Antigen Receptor to Patients With Malignant Gliomas Expressing EGFRvIII
- 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
- EGFRvIII expression promotes oncogenesis and is associated with poor prognosis.
- EGFRvIII is not expressed in normal tissue and is an attractive target for
- 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.
- To evaluate the safety of the administration of anti-EGFRvIII CAR engineered peripheral
blood lymphocytes in patients receiving the non-myeloablative conditioning regimen, and
- 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.
- Determine the in vivo survival of CAR gene-engineered cells.
- Evaluate radiographic changes after treatment
- 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
- The study will be conducted using a Phase I/II design.
- Patients will be accrued to both the phase I and phase II portion of the trial in two
- patients with recurrent malignant glioma requiring steroid use at the start of
- patients with recurrent malignant glioma not requiring steroids at the start of
- 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 for each individual group in the phase I portion of
the trial, the study will proceed to the phase II portion.
- Patients will again be accrued to the same two groups. For each of the 2 groups
evaluated, the study will be conducted using a single stage phase II design.
- A total of 160 patients may be enrolled over a period of 7 years.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the safety and the six month progression free survival in patients administered anti-EGFRlll CAR engineered peripheral blood lymphocytes, the non-myeloablative conditioning regimen, and aldesleukin.
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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