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- Title
Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation.
- Authors
Hexner, Elizabeth; Roboz, Gail; Hoffman, Ron; Luger, Selina; Mascarenhas, John; Carroll, Martin; Clementi, Regina; Bensen‐Kennedy, Debra; Moliterno, Alison
- Abstract
JAK2-V617F is central to the pathogenesis of myeloproliferative neoplasms. We examined whether lestaurtinib decreased JAK2-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 JAK2-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 JAK2-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 JAK2-inhibitor treatment in patients with PV/ ET and highlights both the need for further studies to assess the role of JAK2 inhibition in treatment of PV/ ET and the use of JAK2-V617F as a biomarker for response. This trial was registered at www.clinicaltrials.gov as NCT00586651.
- Subjects
POLYCYTHEMIA; ORAL drug administration; PROTEIN-tyrosine kinase inhibitors; THROMBOCYTOPENIA; MYELOPROLIFERATIVE neoplasms; GENETIC mutation; PATIENTS
- Publication
British Journal of Haematology, 2014, Vol 164, Issue 1, p83
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.12607