The phase 3 EPIC trial, an evaluation of ponatinib (Iclusig) in patients with newly diagnosed chronic myeloid leukemia (CML), is being discontinued due to adverse events.
All trials of ponatinib were placed on partial clinical hold on October 9, after follow-up data from the phase 2 PACE trial revealed an increased incidence of arterial and venous thrombotic events.
That trial involved patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who were resistant to or could not tolerate dasatinib or nilotinib.
The partial clinical hold meant that ponatinib’s makers, Ariad Pharmaceuticals, must pause new enrollment in all ponatinib trials, reduce the doses given to existing patients, and reconsider trial eligibility criteria.
Now, Ariad and the US Food and Drug Administration have agreed that the EPIC trial must be terminated.
“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,” said Timothy P. Clackson, PhD, president of research and development and chief scientific officer at Ariad.
Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physicians. A total of 307 patients were enrolled.
The EPIC trial was a randomized, 2-arm, multicenter study comparing the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries.
Patients had to be at least 18 years of age and diagnosed with CML within 6 months prior to enrollment. Approximately 500 patients were to be randomized 1:1 to the standard dose of ponatinib (45 mg once daily) or imatinib (400 mg once daily).
Increasing the imatinib dose to 600 mg or 800 mg per day was permitted. The primary endpoint of the trial was major molecular response at 12 months of treatment.
Ponatinib is still commercially available in the US and European Union for patients with resistant or intolerant CML and Ph+ ALL. Ariad said it is working with health authorities to make appropriate changes to the product labeling to reflect the safety findings from the PACE trial.
For more information about the changes in ponatinib trials, visit www.clinicaltrials.gov, email inquiries to medinfo@ariad.com, or call the Ariad US toll-free number (855) 552-7423, the European Union toll-free number 800 00027423, or the international number +1 (617)-503-7423.
