Evidence map›Paper›PMID 27634203›Full record

Trial reportHaematologica2017

A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis.

Vikas Gupta, Ruben A Mesa, Michael W N Deininger, Candido E Rivera, Shireen Sirhan, Carrie Baker Brachmann, Helen Collins, Jun Kawashima, Yan Xin, Srdan Verstovsek

Open access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Haematologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 94 citations in OpenAlex.

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  4. SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Vikas GuptaPrincess Margaret Cancer Centre, University of Toronto, ON, Canada vikas.gupta@uhn.on.ca.
Ruben A MesaDivision of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ, USA.
Michael W N DeiningerDivision of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
Candido E RiveraDivision of Hematology/Oncology, Mayo Clinic Jacksonville, FL, USA.
Shireen SirhanDivision of Hematology, Jewish General Hospital, Montreal, QC, Canada.
Carrie Baker BrachmannGilead Sciences, Inc., Foster City, CA, USA.
Helen CollinsGilead Sciences, Inc., Foster City, CA, USA.
Jun KawashimaGilead Sciences, Inc., Foster City, CA, USA.
Yan XinGilead Sciences, Inc., Foster City, CA, USA.
Srdan VerstovsekUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gilead Sciences (United States) · USHuntsman Cancer Institute · USJewish General Hospital · CAMayo Clinic Hospital · USMayo Clinic in Florida · USPrincess Margaret Cancer Centre · CAThe University of Texas MD Anderson Cancer Center · US

Funding

Mechanisms of resistance to ponatinib therapy in chronic myeloid leukemiaR01CA178397 · NCI · UNIVERSITY OF UTAH · PI DEININGER, MICHAEL W., O'HARE, THOMAS J. · 2014 to 2018
$2.6M
NCI NIH HHS R01 CA178397
6 · The paper itself

Abstract

Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058).

Indexed as

AgedAged, 80 and overBenzamidesBiomarkersDrug Administration ScheduleFemaleHumansJanus Kinase 2MaleMiddle AgedPhenotypePrimary MyelofibrosisProtein Kinase InhibitorsPyrimidinesRetreatmentTreatment OutcomeBenzamidesBiomarkersJAK2 protein, humanJanus Kinase 2N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamideProtein Kinase InhibitorsPyrimidines

Identifiers

PMID27634203
PMCPMC5210237
OpenAlexW2521045502

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.