Primary Outcome Measures:
- Feasibility [ Designated as safety issue: No ]
- Safety [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Anti-tumor activity of adoptively transferred clones [ Designated as safety issue: No ]
- Anti-IL 13 zetakine and anti-HyTK immune response in patients
- Efficacy of ganciclovir for clone ablation (in the event of toxicity)
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.