Open‐label study of oral CEP‐701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2‐V617F mutation. (28th October 2013)

• Record Type: Journal Article
• Authors: Hexner, Elizabeth; Roboz, Gail; Hoffman, Ron; Luger, Selina; Mascarenhas, John; Carroll, Martin; Clementi, Regina; Bensen‐Kennedy, Debra; Moliterno, Alison
• Is Part Of: British journal of haematology. Volume 164:Number 1(2014:Jan.)
• Page Start: 83
• Page End: 93
• Publication Date: 2013-10-28
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12607
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12607-abs-0001"> <title>Summary</title> <p> <italic>JAK2‐</italic>V617F is central to the pathogenesis of myeloproliferative neoplasms. We examined whether lestaurtinib decreased <italic>JAK2‐</italic>V617F allele burden and evaluated its clinical benefits and tolerability in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). This phase 2, open‐label, multicentre study was designed to detect ≥15% reduction in <italic>JAK2‐</italic>V617F allele burden in 15% of patients. Eligible patients received lestaurtinib 80 mg twice daily for 18 weeks and could participate in a 1‐year extension phase of treatment. Of 39 enrolled patients, 27 (69%) had PV; 12 (31%) had ET. While the pre‐specified responder rate of 15% was not met, lestaurtinib modestly reduced <italic>JAK2‐</italic>V617F allele burden and reduced spleen size in a subset of patients. Of 37 patients in the full efficacy analysis, 5 (14%) responded clinically. Every patient had ≥1 adverse event, most commonly gastrointestinal (95%). Fifteen patients (38%) experienced serious adverse events; 23 (59%) withdrew due to adverse events. This is the first reported study of <italic>JAK2</italic>‐inhibitor treatment in patients with PV/ET and highlights both the need for further studies to assess the role of <italic>JAK2</italic> inhibition in treatment of PV/ET and the use of <italic>JAK2‐</italic>V617F as a biomarker for response. This trial was registered at www.clinicaltrials.gov as NCT00586651.</p> </abstract>