Oncolytic Adenovirus DNX-2401 in Treating Patients With Recurrent High-Grade Glioma

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PRIMARY OBJECTIVES: I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral super-selective endovascular in...

PRIMARY OBJECTIVES: I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral super-selective endovascular intracranial injection) in patients with recurrent glioblastoma (GBM), gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. II. To determine the local and systemic toxicity of allogeneic BM-hMSCs-DNX2401 administered by intra-arterial injection (i.e., transfemoral super-selective endovascular intracranial injection) in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. III. To determine at the molecular and cellular level the capacity of allogeneic BM-hMSCs-DNX2401 administered intra-arterially to home to and deliver DNX-2401 to recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma by analyzing post-treatment surgical brain tumor specimens for the expression and distribution of adenoviral proteins. SECONDARY OBJECTIVES: I. To assess shedding of adenovirus into the blood, sputum, and nasopharynx after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. II. To assess the development of anti-adenovirus antibodies after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. III. To evaluate immune-mediated cytokine responses after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. IV. To assess anti-tumoral activity and to determine progression-free survival (PFS) and overall survival (OS) after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma. OUTLINE: This is a dose-escalation study. PART I: Patients receive oncolytic adenovirus Ad5-DNX-2401 intra-arterially (IA) over 20-30 minutes on day 0. PART II: Patients receive oncolytic adenovirus Ad5-DNX-2401 as in part I. After 2 weeks, patients undergo surgery, then receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes. After completion of study treatment, patients in part I are followed up on days 1, 4, 7, and 14 of month 1, months 1.5, 3, and 4.5, every 2 months up to month 26, month 30, then every 6 months thereafter. Patients in part II will be followed up on the day after surgery, weeks 1, 2 and 4, months 2, 2.5, 4, 5.5 and 7, every 2 months until month 19, every 4 months until month 32, then every 6 months thereafter.

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