Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies

• Published in: Leukemia & lymphoma Vol. 61; no. 2; pp. 309 - 317
• Main Authors: Siddiqi, Tanya, Frankel, Paul, Beumer, Jan H., Kiesel, Brian F., Christner, Susan, Ruel, Chris, Song, Joo Y., Chen, Robert, Kelly, Kevin R., Ailawadhi, Sikander, Kaesberg, Paul, Popplewell, Leslie, Puverel, Sandrine, Piekarz, Richard, Forman, Stephen J., Newman, Edward M.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 28-01-2020
• Subjects: Alisertib; Aurora kinase; Aurora Kinase A; Azepines; histone deacetylase inhibitor; Histone Deacetylase Inhibitors - therapeutic use; Humans; lymphoma; Lymphoproliferative Disorders - drug therapy; Neoplasm Recurrence, Local; Pyrimidines; vorinostat; Vorinostat - therapeutic use; Aurora kinase; Alisertib; vorinostat; histone deacetylase inhibitor; lymphoma
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2019.1672052

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.