Abstract
Alisertib, an Aurora kinase A inhibitor, was evaluated in a Phase 1 study in combination with the histone deacetylase inhibitor vorinostat, in patients with relapsed/refractory lymphoid malignancies (N = 34; NCT01567709). Patients received alisertib plus vorinostat in 21-day treatment cycles with escalating doses of alisertib following a continuous or an intermittent schedule. All dose-limiting toxicities (DLTs) were hematologic and there were no study-related deaths. The recommended phase 2 dose (RP2D) of the combination was 20 mg bid of alisertib and 200 mg bid of vorinostat on the intermittent schedule. A 13-patient expansion cohort was treated for a total of 18 patients at the RP2D. There were no DLTs at the RP2D, and toxicities were mainly hematologic. Two patients with DLBCL achieved a durable complete response, and two patients with HL achieved partial response. Alisertib plus vorinostat showed encouraging clinical activity with a manageable safety profile in heavily pretreated patients with advanced disease.
Original language | English (US) |
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Pages (from-to) | 309-317 |
Number of pages | 9 |
Journal | Leukemia and Lymphoma |
Volume | 61 |
Issue number | 2 |
DOIs | |
State | Published - Jan 28 2020 |
Keywords
- Alisertib
- Aurora kinase
- histone deacetylase inhibitor
- lymphoma
- vorinostat
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research