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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.


Detailed Summary:

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 an
    Sponsor: City of Hope Medical Center

    Current Primary Outcome:

    • Feasibility [ Time Frame: 1 year after the end of treatment on study ]
    • Safety [ Time Frame: 1 year after the end of treatment on study ]


    Original Primary Outcome:

    • Feasibility
    • Safety


    Current Secondary Outcome:

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


    Original Secondary Outcome:

    • Anti-tumor activity of adoptively transferred clones
    • Anti-IL 13 zetakine and anti-HyTK immune response in patients
    • Efficacy of ganciclovir for clone ablation (in the event of toxicity)


    Information By: City of Hope Medical Center

    Dates:
    Date Received: August 7, 2008
    Date Started: February 2002
    Date Completion:
    Last Updated: August 11, 2011
    Last Verified: August 2011