Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure.

Abstract

Fedratinib is an oral, selective Janus kinase 2 (JAK2) inhibitor. The phase II JAKARTA2 study assessed fedratinib in patients with intermediate- or high-risk myelofibrosis (MF) who were resistant or intolerant to prior ruxolitinib per investigator assessment. Patients received fedratinib 400 mg/day in 28-day cycles. The JAKARTA2 outcomes were initially reported using a last-observation-carried forward (LOCF) analysis in a "Per Protocol" population. This updated analysis of JAKARTA2 employs intention-to-treat analysis principles without LOCF for all treated patients (ITT Population; N = 97), and for a patient subgroup who met more stringent definitions of prior ruxolitinib failure (Stringent Criteria Cohort; n = 79). Median duration of prior ruxolitinib exposure was 10.7 months. The primary endpoint was spleen volume response rate (SVRR; ≥35% spleen volume decrease from baseline to end of cycle 6 [EOC6]). The SVRR was 31% in the ITT Population and 30% in the Stringent Criteria Cohort. Median duration of spleen volume response was not reached. Symptom response rate (≥50% reduction from baseline to EOC6 in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib.

• Authors: Claire N Harrison, Nicolaas Schaap, Alessandro M Vannucchi, Jean-Jacques Kiladjian, Eric Jourdan, Richard T Silver, Harry C Schouten, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Juan Shen, Tymara Berry, Carrie Brownstein, Ruben A Mesa
• Journal: American journal of hematology (Am J Hematol) Vol. 95 Issue 6 Pg. 594-603 (06 2020) ISSN: 1096-8652 [Electronic] United States
• PMID: 32129512 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• Pyrrolidines
• Sulfonamides
• fedratinib
• ruxolitinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Middle Aged
• Nitriles
• Organ Size (drug effects)
• Primary Myelofibrosis (drug therapy, pathology)
• Pyrazoles (administration & dosage)
• Pyrimidines
• Pyrrolidines (administration & dosage)
• Spleen (pathology)
• Sulfonamides (administration & dosage)