A Phase II Study of Nilotinib, a Novel Tyrosine Kinase Inhibitor Administered to Patients with Hypereosiniphilic Syndrome (HES).

Idiopathic hypereosinophilic syndrome (HES) is a rare myeloproliferative disorder characterized by sustained overproduction of eosinophils and organ involvement that can lead to chronic eosinophilic leukemia. HES is a clonal disorder characterized in some patients by constitutive activation of FIP1L1-PDGFRA. There is currently no approved therapy for HES. Nilotinib is a novel aminopyrimidine which potently inhibits Bcr-Abl, as well as the PDGF-R and c-Kit kinases. This Phase II study was designed to evaluate the safety and efficacy of nilotinib administered at an oral dose of 400 mg twice daily to patients with specific HES disease related criteria and with a clinical indication for treatment. Preliminary data are available for 11 patients. The median age is 63 (range 25–77) years. There were 10 males and 1 female. Extramedullary involvement was present in 6 (55%) patients at baseline. Treatment is ongoing for 4 (36%) patients and 7 (64%) have discontinued; 2 (18%) for adverse events; 3 (27%) for disease progression, and 1 (9%) for an administrative reason. There was one patient death due to neutropenic sepsis and endocarditis. Overall, 5 (45%) patients had investigator documented stable disease, and 1 (9%) patient a 51 year old male had a CR. Grade 3 or 4 adverse events included one patient each with rash, decreased hemoglobin, myalgia, arthralgia, pruritis, and diabetes mellitus. In summary, these data suggest that nilotinib has clinical activity and an acceptable safety and tolerability profile in patients with HES.