A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia

B. Vormoor; Gareth J. Veal; M. J. Griffin; Alan V. Boddy; J. Irving; L Minto; M. Case; U Banerji; K. E. Swales; J. R. Tall; A. S. Moore; M. Toguchi; G Acton; K. Dyer; C Schwab; C. J. Harrison; John Grainger; D Lancaster; P. Kearns; D. Hargrave; J. Vormoor

doi:10.1002/pbc.26351

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia

B. Vormoor^*, Gareth J. Veal, M. J. Griffin, Alan V. Boddy, J. Irving, L Minto, M. Case, U Banerji, K. E. Swales, J. R. Tall, A. S. Moore, M. Toguchi, G Acton, K. Dyer, C Schwab, C. J. Harrison, John Grainger, D Lancaster, P. Kearns, D. HargraveJ. Vormoor

^*Corresponding author for this work

Division of Cancer Sciences (L5)

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Abstract

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

Original language	English
Article number	e26351
Journal	Pediatric Blood and Cancer
Volume	64
Issue number	6
Early online date	1 Dec 2016
DOIs	https://doi.org/10.1002/pbc.26351
Publication status	Published - 1 Jun 2017

Keywords

AT9283
aurora kinase
leukemia
pediatric
phase I/II trial

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/pbc.26351

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Vormoor, B., Veal, G. J., Griffin, M. J., Boddy, A. V., Irving, J., Minto, L., Case, M., Banerji, U., Swales, K. E., Tall, J. R., Moore, A. S., Toguchi, M., Acton, G., Dyer, K., Schwab, C., Harrison, C. J., Grainger, J., Lancaster, D., Kearns, P., ... Vormoor, J. (2017). A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia. Pediatric Blood and Cancer, 64(6), Article e26351. https://doi.org/10.1002/pbc.26351

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title = "A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia",

abstract = "Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.",

keywords = "AT9283, aurora kinase, leukemia, pediatric, phase I/II trial",

author = "B. Vormoor and Veal, {Gareth J.} and Griffin, {M. J.} and Boddy, {Alan V.} and J. Irving and L Minto and M. Case and U Banerji and Swales, {K. E.} and Tall, {J. R.} and Moore, {A. S.} and M. Toguchi and G Acton and K. Dyer and C Schwab and Harrison, {C. J.} and John Grainger and D Lancaster and P. Kearns and D. Hargrave and J. Vormoor",

year = "2017",

month = jun,

day = "1",

doi = "10.1002/pbc.26351",

language = "English",

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journal = "Pediatric Blood and Cancer",

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Vormoor, B, Veal, GJ, Griffin, MJ, Boddy, AV, Irving, J, Minto, L, Case, M, Banerji, U, Swales, KE, Tall, JR, Moore, AS, Toguchi, M, Acton, G, Dyer, K, Schwab, C, Harrison, CJ, Grainger, J, Lancaster, D, Kearns, P, Hargrave, D & Vormoor, J 2017, 'A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia', Pediatric Blood and Cancer, vol. 64, no. 6, e26351. https://doi.org/10.1002/pbc.26351

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia. / Vormoor, B.; Veal, Gareth J.; Griffin, M. J. et al.
In: Pediatric Blood and Cancer, Vol. 64, No. 6, e26351, 01.06.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia

T2 - challenges to run early phase clinical trials for children with leukemia

AU - Vormoor, B.

AU - Veal, Gareth J.

AU - Griffin, M. J.

AU - Boddy, Alan V.

AU - Irving, J.

AU - Minto, L

AU - Case, M.

AU - Banerji, U

AU - Swales, K. E.

AU - Tall, J. R.

AU - Moore, A. S.

AU - Toguchi, M.

AU - Acton, G

AU - Dyer, K.

AU - Schwab, C

AU - Harrison, C. J.

AU - Grainger, John

AU - Lancaster, D

AU - Kearns, P.

AU - Hargrave, D.

AU - Vormoor, J.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

AB - Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

KW - AT9283

KW - aurora kinase

KW - leukemia

KW - pediatric

KW - phase I/II trial

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DO - 10.1002/pbc.26351

M3 - Article

SN - 1545-5009

VL - 64

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

IS - 6

M1 - e26351

ER -

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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