Background: Bevacizumab is frequently used to treat recurrent high-grade gliomas, but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects in glioma and may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat in combination with bevacizumab in patients with recurrent grade III and IV gliomas. Methods: Two cohorts were enrolled: one with recurrent glioblastoma (GBM) as the primary study and one with recurrent anaplastic glioma (AG) as the exploratory study. Patients were treated with oral panobinostat 30 mg 3 x per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was 6-month progression-free survival (PFS6) in the GBM cohort and the study was powered to discriminate between a 35% and 55% PFS6 rate (85% power at an alpha level of 0.07). Results: At planned interim analysis, 13 of the first 21 patients accrued to the GBM cohort had progressed within 6 months of initiating study treatment. The GBM cohort did not meet criteria for continued accrual and was closed early. In the GBM cohort, PFS6 rate was 30.4% [95% confidence interval: 12%, 51%], median PFS was 5 months [3, 9], and median OS was 9 months [6, 19]. Accrual in the AG cohort continued to completion and a total of 15 patients were enrolled. In the AG cohort, PFS6 was 46.67% [21%, 73%], median PFS was 7 months [2, 10], and median OS was 17 months [5, 27]. The most common grade 3 or 4 toxicities related to treatment in the GBM arm were hypophosphatemia (12.5%), thrombocytopenia (12.5%), lymphopenia (8.3%), neutropenia (8.3%), and ALT elevation (8.3%). In the AG arm, the most common grade 3 or 4 toxicities were thrombocytopenia (20.0%) and hypophosphatemia (13.3%). There were no deaths related to study treatment. Conclusions: Although reasonably well-tolerated, this phase II study of panobinostat and bevacizumab in recurrent GBM did not meet criteria for continued accrual and the GBM cohort of the study was closed. However, in the recurrent AG cohort, bevacizumab in combination with LBH589 may delay progression. Updated outcome and safety data will be presented. Study supported by Novartis and Genentech. Clinical trial information: NCT00859222.