Autologous CMV-Specific Cytotoxic T Cells and Temozolomide in Treating Patients With Glioblastoma

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PRIMARY OBJECTIVES: I. To determine the maximum feasible dose (MFD) or maximum tolerated dose (MTD) and safety of cytomegalovirus (CMV)-specific T cells in combination with dose-dense temozolomide in patients with recurrent glioblastoma. (Phase I) II. To evaluate the immunological effects in resecte...

PRIMARY OBJECTIVES: I. To determine the maximum feasible dose (MFD) or maximum tolerated dose (MTD) and safety of cytomegalovirus (CMV)-specific T cells in combination with dose-dense temozolomide in patients with recurrent glioblastoma. (Phase I) II. To evaluate the immunological effects in resected glioblastoma after intravenous administered cytomegalovirus (CMV)-stimulated adoptive T cells in patients with recurrent glioblastoma (GBM). (Phase II: recurrent glioblastoma undergoing resection) III. To correlate 6-month progression-free survival rate (PFS6) with objective clearance of CMV antigens as measured by immunohistochemistry (IHC) and by ex vivo T-cell-specific effector responses using intracellular cytokine profiling. (Phase II: recurrent glioblastoma undergoing resection) IV. Overall survival (OS). (Phase II: newly diagnosed glioblastoma) SECONDARY OBJECTIVES: I. Time to progression, overall survival (OS) as well as immunological reactivity and safety. (Phase II: recurrent glioblastoma undergoing resection) II. Safety and tolerability of dose-dense temozolomide in combination with intravenous administered CMV-stimulated adoptive T cells in patients receiving adjuvant therapy after completing external beam radiotherapy with concurrent temozolomide for newly diagnosed glioblastoma. (Phase II: newly diagnosed glioblastoma) III. Overall objective response rate (ORR), median duration of response, PFS6. (Phase II: newly diagnosed glioblastoma) EXPLORATORY OBJECTIVES: I. To determine the persistence and expansion of adoptively-infused CMV-specific T cells by multiparameter flow cytometry in serially-sampled peripheral blood. (Phase I) II. To identify imaging characteristics such as magnetic resonance imaging (MRI) textural analysis associated with immunological changes in tumor following treatment with CMV-stimulated adoptive T cells. (Phase II: recurrent glioblastoma undergoing resection) III. To ascertain if adoptive transfer of CMV-specific T cells leads to the expansion of T cells with specificity to other glioblastoma antigens (i.e. epitope spreading) by performing longitudinally monitoring of antigen-specific T cell frequency with enzyme-linked immunosorbent spot assay (ELISPOT). (Phase II: recurrent glioblastoma undergoing resection) IV. To determine the persistence and expansion of adoptively-infused CMV-specific T cells by multiparameter flow cytometry in serially-sampled peripheral blood. (Phase II: newly diagnosed glioblastoma) OUTLINE: This is a phase I, dose-escalation study of CMV-specific T cells followed by a phase II study. Patients are assigned to 1 of 2 treatment arms. ARM I: Patients receive temozolomide orally (PO) once a day (QD) on days 1-21 and CMV-specific T cell transfer intravenously (IV) over 1-5 minutes on day 22. Patients undergo surgery on day 30 of cycle 1. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-21. Treatment repeats every 42 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive temozolomide PO QD on days 1-21 and CMV-specific T cell transfer intravenously IV over 1-5 minutes on day 22. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 3 months.

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