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
Both
Brain and Central Nervous System Tumors
Trial Information
Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Feasibility
Outcome Time Frame:
1 year after the end of treatment on study
Safety Issue:
No
Principal Investigator
Stephen Forman, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
01020
NCT ID:
NCT00730613
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
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