Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia

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Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia

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Title: Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia
Author: Fathi, Amir T.; Wander, Seth A.; Blonquist, Traci M.; Brunner, Andrew M.; Amrein, Philip C.; Supko, Jeffrey; Hermance, Nicole M.; Manning, Amity L.; Sadrzadeh, Hossein; Ballen, Karen K.; Attar, Eyal C.; Graubert, Timothy A.; Hobbs, Gabriela; Joseph, Christelle; Perry, Ashley M.; Burke, Meghan; Silver, Regina; Foster, Julia; Bergeron, Meghan; Ramos, Aura Y.; Som, Tina T.; Fishman, Kaitlyn M.; McGregor, Kristin L.; Connolly, Christine; Neuberg, Donna S.; Chen, Yi-Bin

Note: Order does not necessarily reflect citation order of authors.

Citation: Fathi, A. T., S. A. Wander, T. M. Blonquist, A. M. Brunner, P. C. Amrein, J. Supko, N. M. Hermance, et al. 2017. “Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia.” Haematologica 102 (4): 719-727. doi:10.3324/haematol.2016.158394. http://dx.doi.org/10.3324/haematol.2016.158394.
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Abstract: Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring “5+2” reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68–96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33–81%) and 42% (90% CI 17–65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. (clinicaltrials.gov Identifier:01779843).
Published Version: doi:10.3324/haematol.2016.158394
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395112/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490922
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