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

This is an interventional treatment trial for Adult Brain Glioblastoma Read More

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)