Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2
Condition: Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor
MeSH terms: Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; Meningioma; Ependymoma; Gliosarcoma; Oligodendroglioma; Hemangiopericytoma; Solitary Fibrous Tumors; Neuroectodermal Tumors, Primitive
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, may stimulate the
      immune system in different ways and stop tumor cells from growing. Donor T cells that are
      treated in the laboratory may be effective treatment for malignant glioma. Aldesleukin may
      stimulate the white blood cells to kill tumor cells. Combining different types of biological
      therapies may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best way to give therapeutic
      donor lymphocytes together with aldesleukin in treating patients with stage III or stage IV
      malignant glioma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess the safety of GRm13Z40-2 CTL CNS loco-regional cellular immunotherapy in
      research participants with recurrent or refractory/ progressive malignant glioma (WHO Grades
      3 or 4).

      II. To assess the safety of convection enhanced delivery (CED) of recombinant human
      Interleukin-2 (rhuIL-2) used in conjunction with GRm13Z40-2 CTL adoptive transfer.

      SECONDARY OBJECTIVES:

      I. To investigate the ability of 9-(4-fluoro-3-hydroxy-methyl-butyl) guanine (18FHBG)
      positron emission tomography PET to image GRm13Z40-2 CTL's in research participants.

      II. To study the impact of concurrent dexamethasone administration on the tempo and magnitude
      of T cell allograft rejection responses in treated research participants by tracking the
      frequency of anti-GRm13Z40-2 immune responses in serially acquired peripheral blood samples.

      III. To evaluate ganciclovir administration for ablating transferred GRm13Z40-2 in vivo
      should significant graft-mediated toxicities be encountered.

      OUTLINE: Patients receive GRm13Z40-2 therapeutic allogeneic lymphocytes intratumorally (IT)
      over 10 minutes on days 1 and 3 and aldesleukin IT over 3 hours on days 2-5 (days 1-5 in week
      2). Treatment repeats every week for 2 courses in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed annually for at least 15 years.
    

Intervention name(s): therapeutic allogeneic lymphocytes; aldesleukin; laboratory biomarker analysis; positron emission tomography
Intervention type(s): Biological; Biological; Other; Procedure
Intervention description(s): Given intratumorally; Given intratumorally; Optional correlative studies; Optional correlative studies
Other intervention name(s): ALLOLYMPH; IL-2; interleukin II; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; TCGF, interleukin; FDG-PET; PET; PET scan; tomography, emission computed
Intervention MeSH terms: Aldesleukin; Interleukin-2
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic meningioma; adult anaplastic oligodendroglioma; adult brain stem glioma; adult ependymoblastoma; adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; adult grade III meningioma; adult meningeal hemangiopericytoma; adult mixed glioma; adult pineal gland astrocytoma; recurrent adult brain tumor; Los Angeles