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) |
|---|---|
| Journal | Leukemia and Lymphoma |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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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 journal › Article
}
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 -