Pilot Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Genetically-Modified Autologous CD8+ T Cell Clones
- 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.
- 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
- To evaluate the efficacy of ganciclovir administration for ablating transferred clones
in vivo should toxicity be encountered.
- 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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
1 year after the end of treatment on study
Stephen Forman, MD
Beckman Research Institute
United States: Food and Drug Administration