The primary objective of this phase 1 trial was to determine the maximum tolerated dose or a recommended dose of oral ponatinib administered once daily. Secondary objectives included safety, antileukemia activity, pharmacokinetics, pharmacodynamics, and potential pharmacogenomic markers. For the dose-escalation portion of the study, patients were assigned to cohorts of at least three patients. Dose escalations in the same patient were allowed up to the dose immediately preceding the highest studied dose, without exceeding the maximum tolerated dose, which was defined as the dose at which a dose-limiting toxic effect occurred in no more than one in six patients.25 (link) Treatment was continued until disease progression, an adverse event leading to cessation, withdrawal of consent, or investigator discretion (Appendix B in the Supplementary Appendix).