EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) for 8 intrathecal (IT) injections (via
lumbar puncture) of anti-cluster of differentiation (CD)3 × anti-EGFRBi armed activated T
cells (aATC) (EGFRBi-armed autologous T cells) given twice per week for 4 weeks in a
standard 3+3 dose escalation schema with 0.10, 0.50 and 1.00 × 10^9 EGFRBi-aATC per IT
injection for a total of 0.8, 4.0, and 8.0 × 10^9 cells, respectively. (Phase I) II. To
explore efficacy and confirm the toxicity profile of EGFRBi-aATC. (Phase II)

SECONDARY OBJECTIVES:

I. Measure immune responses in participants of the phase I/II trial by sequential monitoring
of phenotype, interferon gamma (IFN-g) enzyme-linked immunoSpots (EliSpots),
anti-glioblastoma (GBM) cytotoxicity of peripheral blood mononuclear cell (PBMC) (direct
cytotoxicity against GBM cells) directed at GBM cell lines, T-helper 1 (Th1)/T-helper 2
(Th2) serum cytokine patterns, and anti-glioma antibodies in the cerebrospinal fluid
(CSF)/serum during the "vaccinate and consolidate" process.

II. Assess survival and persistence of aATC in the CSF, and trafficking of IT-injected aATC
out of the CSF into the bloodstream.

III. Image patients' brain with magnetic resonance imaging (MRI) (performed clinically in
2-month intervals; includes standard structural sequences and perfusion imaging) and
alpha-[11C]methyl-L-tryptophan (AMT) positron emission tomography (PET) scan (under Wayne
State University [WSU] Internal Review Board [IRB]/Karmanos Cancer Institute [KCI]-approved
research protocol) before and after the aATC treatment regimen.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

PHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks.

PHASE II: Patients receive EGFRBi-armed autologous T cells* IT twice weekly for 4 weeks and
then intravenously (IV) over 15-30 minutes twice weekly for 2 weeks.

*NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1
prior to first IT infusion.

After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months thereafter.

Inclusion Criteria:

- Histologically-confirmed intracranial glioblastoma or gliosarcoma (World Health
Organization [WHO] grade IV) with evidence of clinical and radiographic (computed
tomography [CT] or MRI brain) tumor progression (need not be biopsy proven)

- Patients who have undergone prior resection, radiation therapy, and/or chemotherapy
(except bevacizumab)

- Karnofsky performance score >= 70 or Eastern Cooperative Oncology Group (ECOG)
performance status = 0 or 1

- Patient agrees to undergo a baseline and a follow-up 11C-alpha-methyl-L-tryptophan
(AMT)-PET scan during immunotherapy (IMT)

- No serious medical or psychiatric illness which prevents informed consent or
intensive treatment is allowed

- Non pregnant: negative serum test for pregnancy, unless male, prior hysterectomy,
tubal ligation, or postmenopausal; (Note: postmenopausal is defined as age > 55 with
amenorrhea for > 1 year or age < 55 years with amenorrhea for 2 years and follicle
stimulating hormone (FSH) level within postmenopausal range of institutional
parameters; patients requiring FSH level to determine menopausal status need not have
this performed and may choose to proceed with serum pregnancy testing)

- Required initial laboratory data (normal limits per treating institution; minor
changes from the indicated laboratory guidelines will be allowed at the discretion of
the treating team under special circumstances and reasons for the changes will be
documented):

- Granulocytes >= 1,000/mm^3

- Absolute lymphocyte count >= 500/mm^3

- Platelet count >= 50,000/ul

- Hemoglobin >= 8 gm/dl

- Blood urea nitrogen (BUN) =< 1.5 times normal

- Serum creatinine < 1.8 mg/dl

- Creatinine clearance >= 50 ml/mm (can be calculated utilizing the Cockcroft & Gault
equation)

- Bilirubin < 1.5 times upper limit of normal

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper
limit of normal

- Alkaline phosphatase < 5 times upper limit of normal

- Prothrombin time (PT) or international normalized ratio (INR) and activated partial
thromboplastin time (aPTT) < 1.2 times upper limit of normal

- Negative human immunodeficiency virus (HIV)-1/2 serology

- Negative hepatitis B surface antigen

- Negative hepatitis C serology

- Left ventricular ejection fraction (LVEF) >= 45% at rest (multi gated acquisition
[MUGA] or echocardiogram [ECHO])

- Each patient must be aware of the nature of their disease and must willingly consent
to treatment after being informed of alternatives, potential benefits, side effects,
and risks

- Surgery is done prior to IMT if needed for palliation, tumor debulking, pathological
documentation of tumor recurrence; the patients may continue on study therapy even if
they do not have measurable disease

- No other investigational agents, immunomodulating agents, or cancer chemotherapy are
permitted for the duration and 12 months following the study IMT unless there is
disease progression; radiotherapy is not permitted; appropriate antibiotics, blood
products, antiemetics, fluids, electrolytes and general supportive care are to be
used as necessary

Exclusion Criteria:

- Resective surgery within 2 months prior to the initial pre-treatment AMT-PET scan

- Severe increased intracranial pressure, status epilepticus, or other serious
complications from the brain tumor, requiring emergency or urgent intervention

- Patients with a history of another malignancy within 5 years of study enrollment

- Patients with extracranial metastases

- Evidence of active bleeding or bleeding diathesis

- Patients will be ineligible for treatment on this protocol if (prior to protocol
entry):

- There is a history of a recent (within one year) myocardial infarction

- There is a current or prior history of angina/coronary symptoms requiring
medications and/or evidence of depressed left ventricular function (LVEF < 45%
by MUGA or ECHO)

- There is clinical evidence of congestive heart failure requiring medical
management (irrespective of MUGA or ECHO results)