Document Detail


A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis.
MedLine Citation:
PMID:  22375971     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis.
METHODS: In this double-blind trial, we randomly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival.
RESULTS: The primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group.
CONCLUSIONS: Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.).
Authors:
Srdan Verstovsek; Ruben A Mesa; Jason Gotlib; Richard S Levy; Vikas Gupta; John F DiPersio; John V Catalano; Michael Deininger; Carole Miller; Richard T Silver; Moshe Talpaz; Elliott F Winton; Jimmie H Harvey; Murat O Arcasoy; Elizabeth Hexner; Roger M Lyons; Ronald Paquette; Azra Raza; Kris Vaddi; Susan Erickson-Viitanen; Iphigenia L Koumenis; William Sun; Victor Sandor; Hagop M Kantarjian
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  366     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-01     Completed Date:  2012-03-08     Revised Date:  2014-06-13    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  799-807     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00952289
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Cell Transformation, Neoplastic
Double-Blind Method
Female
Follow-Up Studies
Humans
Intention to Treat Analysis
Janus Kinase 1 / antagonists & inhibitors*
Janus Kinase 2 / antagonists & inhibitors*
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute / mortality
Male
Middle Aged
Organ Size
Primary Myelofibrosis / drug therapy*,  mortality,  pathology
Protein Kinase Inhibitors / adverse effects,  therapeutic use*
Pyrazoles / adverse effects,  therapeutic use*
Quality of Life
Spleen / drug effects,  pathology
Splenomegaly / drug therapy*
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/INCB018424; 0/Protein Kinase Inhibitors; 0/Pyrazoles; EC 2.7.10.2/Janus Kinase 1; EC 2.7.10.2/Janus Kinase 2
Comments/Corrections
Comment In:
N Engl J Med. 2012 May 24;366(21):2032; author reply 2032-5   [PMID:  22621635 ]
N Engl J Med. 2012 Mar 1;366(9):844-6   [PMID:  22375977 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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