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; G J Veal; M J Griffin; A 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; J D 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, G J Veal, M J Griffin, A 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, J D Grainger, D Lancaster, P Kearns, D HargraveJ Vormoor

Cancer Clinical Trials Unit

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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
Journal	Pediatric Blood & Cancer
Early online date	1 Dec 2016
DOIs	https://doi.org/10.1002/pbc.26351
Publication status	E-pub ahead of print - 1 Dec 2016

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Vormoor_et_al_PhaseI_II_trial_Pediatric_Blood_CancerAccepted author manuscript, 611 KBLicence: None: All rights reserved

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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. D., Lancaster, D., Kearns, P., ... Vormoor, J. (2016). 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 & Cancer. Advance online publication. 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.",

author = "B Vormoor and Veal, {G J} and Griffin, {M J} and Boddy, {A 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 Grainger, {J D} and D Lancaster and P Kearns and D Hargrave and J Vormoor",

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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, JD, Lancaster, D, Kearns, P, Hargrave, D & Vormoor, J 2016, '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 & Cancer. https://doi.org/10.1002/pbc.26351

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, G J

AU - Griffin, M J

AU - Boddy, A 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, J D

AU - Lancaster, D

AU - Kearns, P

AU - Hargrave, D

AU - Vormoor, J

PY - 2016/12/1

Y1 - 2016/12/1

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.

U2 - 10.1002/pbc.26351

DO - 10.1002/pbc.26351

M3 - Article

C2 - 27905678

SN - 1545-5009

JO - Pediatric Blood & Cancer

JF - Pediatric Blood & Cancer

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

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