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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00730613
First received: August 7, 2008
Last updated: August 11, 2011
Last verified: August 2011
  Purpose

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 Intervention
Brain and Central Nervous System Tumors
Biological: therapeutic autologous lymphocytes
Genetic: gene expression analysis
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Feasibility [ Time Frame: 1 year after the end of treatment on study ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 1 year after the end of treatment on study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Anti-tumor activity of adoptively transferred clones [ Time Frame: 1 year after the end of treatment on study ] [ Designated as safety issue: No ]
  • Anti-IL 13 zetakine and anti-HyTK immune response in patients [ Time Frame: 1 year after the end of treatment on study ] [ Designated as safety issue: Yes ]
  • Efficacy of ganciclovir for clone ablation (in the event of toxicity) [ Time Frame: 1 year after the end of treatment on study ] [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: February 2002
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00730613

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Stephen Forman, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Stephen Forman MD, City of Hope Medical Cener
ClinicalTrials.gov Identifier: NCT00730613     History of Changes
Other Study ID Numbers: 01020, P30CA033572, CHNMC-01020, CDR0000590506
Study First Received: August 7, 2008
Last Updated: August 11, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
adult pilocytic astrocytoma
adult anaplastic astrocytoma
adult diffuse 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:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on August 28, 2014