Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies.
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| 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.
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| Authors | Tanya Siddiqi, Paul Frankel, Jan H Beumer, Brian F Kiesel, Susan Christner, Chris Ruel, Joo Y Song, Robert Chen, Kevin R Kelly, Sikander Ailawadhi, Paul Kaesberg, Leslie Popplewell, Sandrine Puverel, Richard Piekarz, Stephen J Forman, Edward M Newman |
| Journal | Leukemia & lymphoma (Leuk Lymphoma) Vol. 61 Issue 2 Pg. 309-317 (02 2020) ISSN: 1029-2403 [Electronic] United States |
| PMID | 31617432 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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