Table 3.

Aurora kinase inhibitors currently in clinical development in CML and Ph+ ALL

Drug	Clinical trial	Patients included	N	Route	Dose	Main toxicity reported	Responses	Reference
AT9283	Phase I/II	Refractory AML, MDS, ALL, CML, MF	NR	IV	NR	NR	NR	NCT00522990*
Danusertib	Phase I	Advanced-stage CML**, Ph+ ALL**	23	IV	90–200 mg/m2 /day × 7d q 2 weeks (MTD not reached)	Diarrhoea, nausea, pyrexia, fainting, headache	5 HR, 1 CCR, 1 PCR, 1 MCR, 1 CMolR	Cortes-Franco et al, (2009)
	Phase II	CML, relapsed after prior RTK inhibitors	NR	IV	NR	NR	NR	NCT00335868*
XL228	Phase I	Refractory CML**, Ph+ ALL	27	IV	0.45–10.8 mg/kg weekly or twice weekly (MTD not reached)	Syncope, hyperglycaemia, nausea, vomiting, fatigue.	3 (2 with T315I) decrease BCR-ABL1 by > 1 logarithm	Cortes et al, (2008a)
AS703569	Phase I	AML, MDS, CML**, MPD	45	PO	3–47 mg/m2/d×6d q 21 days	Neutropenia, thrombocytopenia, mucositis, diarrhoea, infection	1/6 CML with T315I cytogenetic response	Sonet et al, (2008)
KW-2449	Phase I	AML, MDS, ALL, CML**	29	PO	12.5–500 mg bid (Trial stopped early; MTD not reached)	Pneumonia, dyspnea, cardiac arrhythmia, cardiac ischaemia.	1/5 CML disappearance of T315I clone.	Pratz et al, (2009)

AML, acute myeloid leukaemia; MDS, myelodysplasia; CML, chronic myeloid leukaemia; MPD, myeloproliferative disease; MF, myelofibrosis; ALL, acute lymphoblastic leukaemia; IV intravenous injection; PO, oral; bid, twice daily; MTD, maximum tolerated dose; HR, haematological remission; CCR, complete cytogenetic response; PCR, partial cytogenetic response; MCR, minor cytogenetic response; CMolR, complete molecular response; NR, not reported.

^*ClinicalTrials.gov Identifier number (cited where no report is available).

^**Trials that have reported clinical activity in CML patients with T315I mutations (see text).