Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial

Animesh D Pardanani, Claire Harrison, Jorge E. Cortes, Francisco Cervantes, Ruben A. Mesa, Donald Milligan, Tamás Masszi, Elena Mishchenko, Eric Jourdan, Alessandro M. Vannucchi, Mark W. Drummond, Mindaugas Jurgutis, Kazimierz Kuliczkowski, Emanuil Gheorghita, Francesco Passamonti, Frank Neumann, Abhay Patki, Guozhi Gao, Ayalew Tefferi

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (≥18 years of age) with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles.

MAIN OUTCOMES AND MEASURES: The primary end point was spleen response (≥35% reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography) at week 24 and confirmed 4 weeks later. The main secondary end point was symptom response (≥50% reduction in total symptom score, assessed using the modified Myelofibrosis Symptom Assessment Form).

IMPORTANCE: Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinically beneficial activity in patients with MF in early-phase trials.

OBJECTIVE: To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF.

RESULTS: The primary end point was achieved by 35 of 96 (36% [95% CI, 27%-46%]) and 39 of 97 (40% [95% CI, 30%-50%]) patients in the fedratinib 400-mg and 500-mg groups, vs 1 of 96 (1% [95% CI, 0%-3%]) in the placebo group (P 

CONCLUSIONS AND RELEVANCE: Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued.

TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01437787.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalJAMA oncology
Volume1
Issue number5
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Pardanani, A. D., Harrison, C., Cortes, J. E., Cervantes, F., Mesa, R. A., Milligan, D., Masszi, T., Mishchenko, E., Jourdan, E., Vannucchi, A. M., Drummond, M. W., Jurgutis, M., Kuliczkowski, K., Gheorghita, E., Passamonti, F., Neumann, F., Patki, A., Gao, G., & Tefferi, A. (2015). Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA oncology, 1(5), 643-651. https://doi.org/10.1001/jamaoncol.2015.1590