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Cellular Adoptive Immunotherapy Using Genetically Modified T-Lymphocytes in Treating Patients With Recurrent or Refractory High-Grade Malignant Glioma

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ClinicalTrials.gov Identifier: NCT00730613
Recruitment Status : Completed
First Posted : August 8, 2008
Last Update Posted : October 9, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:

RATIONALE: Cellular adoptive immunotherapy may stimulate the immune system in different ways and stop cancer cells from growing.

PURPOSE: This clinical trial is studying the side effects of cellular adoptive immunotherapy using genetically modified T-lymphocytes and to see how well it works in treating patients with recurrent or refractory high-grade malignant glioma.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Biological: therapeutic autologous lymphocytes Genetic: gene expression analysis Other: laboratory biomarker analysis Phase 1

Detailed Description:



  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones
Study Start Date : February 2002
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Arm Intervention/treatment
Experimental: Treatment (therapeutic autologous lymphocytes)
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.
Biological: therapeutic autologous lymphocytes
Cycles of escalating cell dose infusions up to the target cell dose of 10(8)

Genetic: gene expression analysis
At the time of excess pathology samples documenting response/relapse

Other: laboratory biomarker analysis
CSF generated at the time of each T-cell dose

Primary Outcome Measures :
  1. Feasibility [ Time Frame: 1 year after the end of treatment on study ]
  2. Safety [ Time Frame: 1 year after the end of treatment on study ]

Secondary Outcome Measures :
  1. Anti-tumor activity of adoptively transferred clones [ Time Frame: 1 year after the end of treatment on study ]
  2. Anti-IL 13 zetakine and anti-HyTK immune response in patients [ Time Frame: 1 year after the end of treatment on study ]
  3. Efficacy of ganciclovir for clone ablation (in the event of toxicity) [ Time Frame: 1 year after the end of treatment on study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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 toxicity
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00730613

Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
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Principal Investigator: Stephen Forman, MD City of Hope Comprehensive Cancer Center
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00730613    
Other Study ID Numbers: 01020
P30CA033572 ( U.S. NIH Grant/Contract )
CDR0000590506 ( Registry Identifier: NCI PDQ )
First Posted: August 8, 2008    Key Record Dates
Last Update Posted: October 9, 2017
Last Verified: October 2017
Keywords provided by City of Hope Medical Center:
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
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases