Clinical Trial Finder

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)

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.

Arms

Experimental: Treatment (EGFRBi-armed autologous T cells)

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 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.

Interventions

Biological: - EGFRBi-Armed Autologous T Cells

Given IT and IV

Other: - Laboratory Biomarker Analysis

Correlative studies