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

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Aurora Kinase A
Histone Deacetylase Inhibitors
Neoplasms
Appointments and Schedules
vorinostat
MLN 8237
Safety

Keywords

  • Alisertib
  • Aurora kinase
  • histone deacetylase inhibitor
  • lymphoma
  • vorinostat

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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

In: Leukemia and Lymphoma, 01.01.2019.

Research output: Contribution to journalArticle

Siddiqi, T, Frankel, P, Beumer, JH, Kiesel, BF, Christner, S, Ruel, C, Song, JY, Chen, R, Kelly, KR, Ailawadhi, S, Kaesberg, P, Popplewell, L, Puverel, S, Piekarz, R, Forman, SJ & Newman, EM 2019, 'Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies', Leukemia and Lymphoma. https://doi.org/10.1080/10428194.2019.1672052
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. / Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies. In: Leukemia and Lymphoma. 2019.
@article{11b289bee6f2433bbb474111e047efdc,
title = "Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies",
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.",
keywords = "Alisertib, Aurora kinase, histone deacetylase inhibitor, lymphoma, vorinostat",
author = "Tanya Siddiqi and Paul Frankel and Beumer, {Jan H.} and Kiesel, {Brian F.} and Susan Christner and Chris Ruel and Song, {Joo Y.} and Robert Chen and Kelly, {Kevin R.} and Sikander Ailawadhi and Paul Kaesberg and Leslie Popplewell and Sandrine Puverel and Richard Piekarz and Forman, {Stephen J.} and Newman, {Edward M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/10428194.2019.1672052",
language = "English (US)",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies

AU - Siddiqi, Tanya

AU - Frankel, Paul

AU - Beumer, Jan H.

AU - Kiesel, Brian F.

AU - Christner, Susan

AU - Ruel, Chris

AU - Song, Joo Y.

AU - Chen, Robert

AU - Kelly, Kevin R.

AU - Ailawadhi, Sikander

AU - Kaesberg, Paul

AU - Popplewell, Leslie

AU - Puverel, Sandrine

AU - Piekarz, Richard

AU - Forman, Stephen J.

AU - Newman, Edward M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Alisertib

KW - Aurora kinase

KW - histone deacetylase inhibitor

KW - lymphoma

KW - vorinostat

UR - http://www.scopus.com/inward/record.url?scp=85074359850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074359850&partnerID=8YFLogxK

U2 - 10.1080/10428194.2019.1672052

DO - 10.1080/10428194.2019.1672052

M3 - Article

C2 - 31617432

AN - SCOPUS:85074359850

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

ER -