White Blood Cells With Anti-EGFR-III for Malignant Gliomas
- 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.
- To see if anti-EGFR white blood cells are a safe and effective treatment for advanced gliomas.
- 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.
- 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.
Biological: Anti-EGFRvIII CAR transduced PBL
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- 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 and todetermine the six month progression free surviv... [ Time Frame: approximately 7 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||September 2019 (Final data collection date for primary outcome measure)|
Experimental: Single Arm
Patients will receive a non-myeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of anti- EGFRvIII CAR transduced PBL, plus IV aldesleukin.
Biological: Anti-EGFRvIII CAR transduced PBL
On day 0 (one to four days after the last dose of fludarabine),cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.Drug: Aldesleukin
Aldesleukin(based on total body weight) 72,000 IU/kg IV over 15 minute approximately every eight hours (+/- one hour) beginning within 24 hours of cell infusion and continuing for up to 5 days maximum of 15 doses).Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
- 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.
- 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.
- 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01454596
|Contact: June Kryk, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 email@example.com|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|