Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

This is an interventional treatment trial for Anaplastic Astrocytoma focused on measuring adult anaplastic astrocytoma, adult anaplastic ependymoma, adult anaplastic meningioma, adult anaplastic oligodendroglioma, adult brain stem glioma, adult ependymoblastoma, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult grade III meningioma, adult meningeal hemangiopericytoma, adult mixed glioma, adult pineal gland astrocytoma, recurrent adult brain tumor, Los Angeles Read More

Inclusion Criteria:

• Histological verification of grade III or IV MG at original diagnosis
• Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of radiation therapy
• Expression of IL13Ralpha2 by immunohistochemistry
• Karnofsky performance status (KPS) >= 60

• Disease recurrence/progression in the cerebral hemisphere, which is in at least one area of enhancement amenable to biopsy after protocol enrollment in the following locations:

  • Adjacent or near previous resection cavity
  • Distant from primary location; this includes tumor spread to contralateral hemisphere, corpus callosum, thalamus, basal ganglion, or subependymal locations
• Research participant has recovered from toxicity of prior therapies; an interval of at least 12 weeks must have elapsed since the completion of radiation therapy; at least 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen; and at least 4 weeks since the completion of a non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only, and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment
• History of prior treatment with Temodar if no evidence of intolerance; documentation of intolerance to Temodar is not required
• Creatinine < 1.6
• White blood cell (WBC) >= 2,000/dl (or absolute neutrophil count [ANC] > 1,000) Platelets >= 100,000/dl unsupported by transfusion or growth factor, international normalized ratio (INR) < 1.3
• Bilirubin < 1.5
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) < 2 X upper limits of normal
• Female research participants of childbearing potential must not be pregnant as evidenced by a serum beta-HCG pregnancy test obtained within 7 days of enrollment
• Research participants having reproductive potential must agree to use effective contraception during participation on this protocol
• In the opinion of the neurosurgeon, research participant requires on-going dexamethasone therapy

Exclusion Criteria:

• Survival expectation less than 4 weeks
• Pulmonary- Requirement for supplemental oxygen use that is not expected to resolve within 2 weeks, Cardiac- Uncontrolled cardiac arrhythmia, hypotension requiring pressor support, Renal- Dialysis dependent, Neurologic- refractory seizure disorder, clinically evident progressive encephalopathy

• Tumors with the following characteristics:

  • Large tumor recurrence causing significant symptoms from brain shift or mass effect, and thus not requiring "decompressive" craniotomy
  • Tumors located primarily in the basal ganglion or thalamus
  • Tumors with significant involvement of midbrain, cerebellum, pons and medulla will be excluded due to neurological risks associated with edema exacerbation from therapy
• Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
• Positive human immunodeficiency virus (HIV) serology based on testing within 4 weeks of enrollment
• Research participants being treated for severe infection or who are recovering from major surgery are ineligible until recovery is deemed complete by the investigator
• Failure to understand the basic elements of the protocol and/or the risks/benefits of participating in this pilot study
• History of ganciclovir and/or magnetic resonance imaging (MRI) contrast allergy or intolerance History of intolerance to IL-2