NCT01454596

CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with gliomas that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient's white blood cells with a retrovirus that has the gene for epidermal growth factor receptor (EGFR) vIII incorporated in the retrovirus. Objective: The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-EGFRvIII cells) are a safe and effective treatment for advanced gliomas. Eligibility: \- Adults age 18-70 with malignant glioma expressing the EGFRvIII molecule. Design: Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-EGFRvIII cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-EGFRvIII cells, and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans every month for the first year, and then every 1-2 months as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Detailed description

BACKGROUND: \- Patients with recurrent gliomas have very limited treatment options. Epidermal growth factor receptor (EGFR). (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, lymphodepleting preparative 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, lymphodepleting preparative regimen. ELIGIBILITY: * Histologically proven glioblastoma or gliosarcoma expressing EGFRvIII as determined by immunohistochemistry (IHC) or Reverse transcription polymerase chain reaction (RT-PCR) * Failed prior standard treatment with radiotherapy with or without chemotherapy * Karnofsky performance score (KPS) 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, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumorreactive, CAR gene-transduced peripheral blood mononuclear cells (PBMC), plus intravenous (IV) aldesleukin. * Once the maximum tolerated cell dose (MTD) has been determined, the study will proceed to the phase II portion. * In the phase II portion of the trial, patients will be accrued to two cohorts: * Patients with recurrent malignant glioma receiving steroids at the time of treatment. * Patients with recurrent malignant glioma not receiving steroids at the time of treatment. * A total of 107 patients may be enrolled over a period of 7 years.

Conditions

• Malignant Glioma
• Glioblastoma
• Brain Cancer
• Gliosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	Epidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL	Day 0: Cells will be infused intravenously over 20-30 minutes. Patients will receive two cell doses, 2 hours apart.
DRUG	Aldesleukin	Aldeskeukin 72,000 IU /kg intravenous (IV) or 720,000 IU /kg IV (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).
DRUG	Fludarabine	Days -7 to -3: Fludarabine 25 mg /m(2)/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
DRUG	Cyclophosphamide	Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg /day X 2 days over 1 hr.

Timeline

• Start date: 2012-05-16
• Primary completion: 2018-11-01
• Completion: 2019-01-17
• First posted: 2011-10-19
• Last updated: 2019-08-21
• Results posted: 2019-08-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study