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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

Phase 1
18 Years
70 Years
Open (Enrolling)
Anaplastic Astrocytoma, Anaplastic Ependymoma, Anaplastic Meningioma, Anaplastic Oligodendroglioma, Brain Stem Glioma, Ependymoblastoma, Giant Cell Glioblastoma, Glioblastoma, Gliosarcoma, Grade III Meningioma, Meningeal Hemangiopericytoma, Mixed Glioma, Pineal Gland Astrocytoma, Brain Tumor

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Trial Information

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


I. To assess the safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy in
research participants with recurrent or refractory/ progressive malignant glioma (WHO Grades
3 or 4).

II. To assess the safety of convection enhanced delivery (CED) of recombinant human
Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer.


I. To investigate the ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG)
positron emission tomography PET to image GRm13Z40-2 CTL's in research participants.

II. To study the impact of concurrent dexamethasone administration on the tempo and
magnitude of T cell allograft rejection responses in treated research participants by
tracking the frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral
blood samples.

III. To evaluate ganciclovir administration for ablating transferred GRm13Z40-2 in vivo
should significant graft-mediated toxicities be encountered.

OUTLINE: Patients receive GRm13Z40-2 therapeutic allogeneic lymphocytes intratumorally (IT)
over 10 minutes on days 1 and 3 and aldesleukin IT over 3 hours on days 2-5 (days 1-5 in
week 2). Treatment repeats every week for 2 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed annually for at least 15 years.

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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy

Outcome Time Frame:

Daily for first 2 weeks, weekly for month 1, every other week for month 2 , monthly for 6 months

Safety Issue:


Principal Investigator

Behnam Badie

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

May 2010

Completion Date:

Related Keywords:

  • Anaplastic Astrocytoma
  • Anaplastic Ependymoma
  • Anaplastic Meningioma
  • Anaplastic Oligodendroglioma
  • Brain Stem Glioma
  • Ependymoblastoma
  • Giant Cell Glioblastoma
  • Glioblastoma
  • Gliosarcoma
  • Grade III Meningioma
  • Meningeal Hemangiopericytoma
  • Mixed Glioma
  • Pineal Gland Astrocytoma
  • Brain Tumor
  • 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
  • Astrocytoma
  • Brain Neoplasms
  • Ependymoma
  • Glioblastoma
  • Glioma
  • Hemangiopericytoma
  • Meningioma
  • Oligodendroglioma
  • Gliosarcoma
  • Neuroectodermal Tumors, Primitive



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