 Patients receive pevonedistat intravenously IV over 60 minutes on days 1, 8, 10, and 12, temozolomide orally PO daily on days 8 -12, and irinotecan hydrochloride IV over 90 minutes on days 8-12 of course 1. Beginning at course 2, patients receive pevonedistat IV over 60 minutes on days 1, 3, and 5, temozolomide PO daily on days 1-5, and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment repeats every 28 days for course 1 and 21 days for subsequent courses for up to 17 courses in the absence of disease progression or unacceptable toxicity. 