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Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones

18 Years
70 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones



- To assess the feasibility and safety of cellular immunotherapy utilizing ex vivo
expanded autologous CD8-positive T-cell clones genetically modified to express the
IL-13 zetakine chimeric immunoreceptor and the Hy/TK selection/suicide fusion protein
in patients with recurrent or refractory, high-grade malignant glioma.


- To evaluate the antitumor activity of adoptively transferred clones in these patients.

- To screen for the development of anti-IL13 zetakine and anti-HyTK immune responses in
these patients.

- To evaluate the efficacy of ganciclovir administration for ablating transferred clones
in vivo should toxicity be encountered.


- Leukapheresis and therapy preparation: Patients undergo leukapheresis to obtain
peripheral blood mononuclear cells. T-cells isolated from the peripheral blood are then
genetically modified, hygromycin-resistant cloned, expanded ex vivo, and cryopreserved
until the first clinical or radiographic evidence of recurrence or progression.
Patients with documented disease recurrence or progression undergo re-biopsy or
re-resection of the tumor and placement of a reservoir-access device (Rickham shunt)
into the tumor resection cavity prior to autologous T-cell clone infusion therapy.

- Autologous T-cell clone infusion: Patients receive an infusion of autologous
antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and
5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the
absence of disease progression or unacceptable toxicity. Patients achieving tumor
regression with residual disease by MRI after 4 courses of study therapy may receive up
to 2 additional courses in the absence of disease progression, unacceptable toxicity,
or a complete response.

Patients undergo blood, cerebrospinal fluid, and tissue sample collection periodically for
correlative studies. Samples are assessed for IL13Rα2 expression levels, susceptibility to
redirected T-cell effector mechanisms, and other tumor and T-cell activation markers.

After completion of study treatment, patients will be followed monthly for 3 months, then
every 3 months for two years, and then annually for at least 15 years.

Inclusion Criteria


- Histologically confirmed malignant glioma at original diagnosis

- Grade III or IV disease

- Refractory or recurrent disease

- Unifocal site of original disease in cerebral cortex

- No clinical evidence of progressive encephalopathy

- Has not undergone recent re-resection of recurrent or progressive disease

- No communication between the tumor resection cavity and the ventricles and deep
cerebrospinal fluid pathways as documented by post-operative MRI scan


- Karnofsky performance status 70-100%

- Life expectancy > 3 months

- WBC ≥ 2,000/dL

- ANC > 1,000/dL

- Platelet count ≥ 100,000/dL (unsupported by transfusion or growth factor)

- Creatinine < 1.6 mg/dL

- Bilirubin < 1.5

- SGOT and SGPT < 2 times upper limit of normal

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to understand protocol basic elements and/or risks/benefits of participating in
this pilot study

- No requirement for supplemental oxygen to keep saturation > 95% that is not expected
to resolve within 2 weeks

- No uncontrolled cardiac arrhythmia

- No hypotension requiring pressor support

- No renal dialysis dependency

- No refractory seizure disorder

- No concurrent non-malignant illness that is poorly controlled with treatment or is of
such severity the investigators deem it unwise to enter the patient on protocol

- No severe infection for which patient is being treated

- No history of ganciclovir and/or Prohance contrast allergy or intolerance

- No HIV positivity within the past 3 months


- See Disease Characteristics

- Must have recovered from major surgery

- At least 4 weeks since primary therapy and no steroid dependence

- At least 2 weeks since prior adjuvant cytotoxic chemotherapy and recovered

- No concurrent systemic corticosteroids, except for use in managing T-cell therapy

- No concurrent immunotherapy (i.e., interferons, vaccines, or other cellular products)

- No concurrent pentoxifylline

- No other concurrent investigative agents

- No concurrent ganciclovir or ganciclovir derivative

- No concurrent acyclovir for non-life threatening herpes virus infection

Type of Study:


Study Design:

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

Outcome Measure:


Outcome Time Frame:

1 year after the end of treatment on study

Safety Issue:


Principal Investigator

Stephen Forman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2002

Completion Date:

August 2011

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic astrocytoma
  • adult diffuse astrocytoma
  • adult pilocytic astrocytoma
  • adult subependymal giant cell astrocytoma
  • adult anaplastic ependymoma
  • adult ependymoma
  • adult myxopapillary ependymoma
  • adult subependymoma
  • adult anaplastic oligodendroglioma
  • adult oligodendroglioma
  • adult brain stem glioma
  • adult giant cell glioblastoma
  • adult glioblastoma
  • recurrent adult brain tumor
  • adult gliosarcoma
  • adult mixed glioma
  • adult pineal gland astrocytoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms