Hello, my name is Jorge Cortes. I am the deputy chair of the Department of Leukemia at the MD Anderson in Houston. I also chair the CML and the AML sections for the same department. I want to talk to you about a clinical trial that is ongoing now which is for the use of ponatinib as initial therapy for the patients with chronic myeloid leukemia that have features of accelerated phase at the time of diagnosis. As we know, the overwhelming majority of patients with chronic myeloid leukemia when they are diagnosed have chronic phase. However, there are a small percentage of patients that have features of accelerated phase, and there is no established treatment for these patients. So, this study is meant to investigate treatment for these particular subsets of patients. The design of the study is that patients with these features, and these features accelerated phase is defined as a basophil count in the peripheral blood on the bone marrow of 20% or greater or a blast count of 15% or greater up to 29%, above that is blast phase which is not included in these trials, or a platelet count that is less than 100,000 unrelated to therapy, or that they have clonal evolution that means addition of chromosomal abnormalities in addition to the Philadelphia chromosome. So, with any of these features at the time of diagnosis that have not received prior therapies, certainly not with the tyrosine kinase inhibitor, they can be enrolled in the study. They will be taking ponatinib which as you know is very effective in the setting of having received prior therapies for CML, prior tyrosine kinase inhibitors. In this study, we are using a starting dose now of 30 mg daily. As you know, the initially approved dose was 45 mg daily. There were some atherothrombotic events with that dose. Therefore, we are electing to start with a lower dose of 30 mg daily, and these doses are adjusted according to safety features. We also are selecting patients according to any cardiovascular events, so patients who have had recent cardiovascular events, for example a myocardial infarction within six months or peripheral arterial occlusive disease or recent angina. These patients are excluded. Similarly, patients that have a cerebrovascular event are also excluded from these trials. So, the patients then receive, as I mentioned, ponatinib 30 mg daily. We monitor them for response with a bone marrow aspiration and with cytogenetics and with PCR every three months for the first year and then every six months after that. Most of the monitoring in between those visits is done by local treating referring physicians, and only these key assessments for response are done centrally. We are going to be monitoring the patients with electrocardiograms and echocardiograms so as to be mindful of the safety of the ponatinib, and the goal is to see if we can have a high rate of a complete cytogenic response for these patients. The treatment continues indefinitely as long as the patients are deriving benefit and not having unacceptable toxicity for the study, and the drug is provided by the study for the duration of the participation of the patients. So, we think that this study fills a void in terms of the management of these subsets of the patients, which as I mentioned is not a large number of patients, but we do see these patients occasionally, and we want to develop a valid treatment so that these patients can have as good an outcome as we have now for patients with a chronic-phase chronic myeloid leukemia at the time of diagnosis. So, the study is open at MD Anderson, it is a single institution phase II study. I am the principal investigator, and we are enrolling right now for this study. I thank you for your attention.
ClinicalTrials.gov Identifier NCT01570868. Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP) https://clinicaltrials.gov/ct2/show/NCT01570868