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

Inclusion Criteria

-INCLUSION CRITERIA:

1. Patients with histologically proven glioblastomas or gliosarcomas that express
EGFRvIII as assessed by IHC or PCR.

2. Patients must have progression of disease after radiotherapy (including patients that
undergo surgery for recurrent disease and are rendered NED). This includes recurrent
GBM after receiving all standard first-line treatment, including surgery (if feasible
due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy
+/- chemotherapy.

3. Patients must either not be receiving steroids, or be on a stable dose of steroids
for at least five days prior to registration.

4. Patients must be > 18 years old, and must have a life expectancy > 8 weeks

5. Patients must be able to understand and sign the Informed Consent Document

6. Must be willing to sign a durable power of attorney.

7. Patients must have a Karnofsky performance status of greater than or equal to 60

8. Patients of both genders must be willing to practice birth control for four months
following the preparative regimen.

9. Serology:

- Seronegative for HIV antibody. (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive can have decreased immune-competence and thus be less responsive to
the experimental treatment and more susceptible to its toxicities.)

- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody
unless antigen negative.

10. Hematology

- WBC greater than or equal to 3000/mm(3)

- ANC greater than or equal to 1000/mm(3) without the support of filgrastim

- Platelet count greater than or equal to 100,000/mm(3)

- Hemoglobin greater than or equal to 8.0 g/dl (eligibility level for hemoglobin
may be reached by transfusion)

11. Chemistry:

- ALT/AST less than or equal to to 2.5 times the upper limit of normal

- Creatinine less than or equal to to 1.6 mg/dl

- Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with
Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

12. Patients must be at least 4 weeks from radiation therapy. Additionally, patients must
be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from
procarbazine, 2 weeks from vincristine and 4 weeks from last bevacizumab
administration. Patients must be at least 4 weeks from other cytotoxic therapies not
listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen)
including investigative agents. All toxicities from prior therapies should be
resolved to CTCAE less than or equal to grade 1 (except for toxicities such as
alopecia, or vitiligo).

EXCLUSION CRITERIA:

1. A prior history of gliadel implantation in the past six months..

2. Women who are currently pregnant or breast feeding because of the potentially
dangerous effects of the preparative regimen on the fetus or infant.

3. Active systemic infections, coagulation disorders or other major medical illnesses
including those of the cardiovascular, respiratory or immune system, myocardial
infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease.

4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
Disease).

5. 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).

6. History of severe immediate hypersensitivity to any of the agents including

cyclophosphamide, fludarabine, or aldesleukin.

7. History of coronary revascularization or ischemic symptoms.

8. 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 CT to exclude acute bleeding.

9. Other concomitant anti-cancer therapy except corticosteroids.

10. Any patient known to have an LVEF less than or equal to 45%.

11. Documented FEV1 less than or equal to 60% predicted tested in patients with:

- A prolonged history of cigarette smoking (20 pk/year of smoking within thepast 2
years).

- Symptoms of respiratory dysfunction