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

Completed · Phase 1/Phase 2

Conditions studied: Malignant Glioma, Glioblastoma, Brain Cancer, Gliosarcoma

In brief

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.

Key facts

Study ID

NCT01454596

Run by

National Cancer Institute (NCI)

People needed

18

Starts

2012-05-16

Expected to finish

2019-01-17

Last updated by the study team

2019-08-21

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• A prior history of gliadel implantation in the past six months..
• Women of child-bearing potential who are pregnant or breast feeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Active systemic infections, requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
• History of coronary revascularization or ischemic symptoms.
• Clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criteria; patients who with history of prior intratumoral bleeding, however, need to undergo a non-contrast head computed tomography (CT) to exclude acute bleeding.
• Other concomitant anti-cancer therapy except corticosteroids.
• Any patient known to have left ventricular ejection fraction (LVEF) less than or equal to 45%.
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history, with cessation within the past two years).
• Symptoms of respiratory dysfunction
• Patients who are receiving any other investigational agents.
• Documented LVEF less than or equal to 45% tested in patients:
• Age greater than or equal to 65 years
• With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease and/or chest pain.

Where it is running

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

Full record on ClinicalTrials.gov

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