Brain and Central Nervous System TumorsPhase 1NCT00730613

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

A Phase 1 study testing therapeutic autologous lymphocytes, gene expression analysis and laboratory biomarker analysis in people with Brain and Central Nervous System Tumors, run by City of Hope Medical Center.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Brain and Central Nervous System Tumors
What is being tested?: therapeutic autologous lymphocytes, gene expression analysis and laboratory biomarker analysis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: No sites listed yet
Study dates: 25 Mar 2002to 1 Aug 2011
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

About this study

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

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.

Read the detailed description

OBJECTIVES:

Primary

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.

Secondary

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.

OUTLINE:

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.

Conditions: Brain and Central Nervous System Tumors
Being tested: therapeutic autologous lymphocytes, gene expression analysis, laboratory biomarker analysis
Keywords: 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
Medical subject headings: Central Nervous System Neoplasms, Astrocytoma, Ependymoma, Glioma, Subependymal, Oligodendroglioma, Glioblastoma, Brain Neoplasms, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

therapeutic autologous lymphocytesBiological
Cycles of escalating cell dose infusions up to the target cell dose of 10(8)
gene expression analysisGenetic
At the time of excess pathology samples documenting response/relapse
laboratory biomarker analysisOther
CSF generated at the time of each T-cell dose

Study groups in NCT00730613
Study group	Role	What they receive
Treatment (therapeutic autologous lymphocytes)	Experimental	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. Receives: Biological: therapeutic autologous lymphocytes; Genetic: gene expression analysis; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

Feasibility
Measured: 1 year after the end of treatment on study
Safety
Measured: 1 year after the end of treatment on study

Secondary outcomes (3)

Anti-tumor activity of adoptively transferred clones
Measured: 1 year after the end of treatment on study
Anti-IL 13 zetakine and anti-HyTK immune response in patients
Measured: 1 year after the end of treatment on study
Efficacy of ganciclovir for clone ablation (in the event of toxicity)
Measured: 1 year after the end of treatment on study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Mar 20021 Aug 2011

First posted8 Aug 2008 (estimated)
Study start25 Mar 2002
Primary completion1 Aug 2011
Study completion1 Aug 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00730613
Sponsor's protocol ID: 01020
Other IDs: P30CA033572, CHNMC-01020, CDR0000590506
Status last verified: Sep 2026
First submitted: 7 Aug 2008
Last updated: 1 Oct 2026
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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