Evidence map›Paper›PMID 27479177›Full record

Trial reportLeukemia2017

A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis.

S Verstovsek, M Talpaz, E Ritchie, M Wadleigh, O Odenike, C Jamieson, B Stein, T Uno, R A Mesa

Open access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 43 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. New approaches to tackle cytopenic myelofibrosis.Hematology. American Society of Hematology. Education Program · 2022
    Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Fedratinib in myelofibrosis.Blood advances · 2020
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Developmental Therapeutics in Myeloproliferative Neoplasms.Clinical lymphoma, myeloma & leukemia · 2017
    Review
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

9 authors at 8 institutions in 1 country.

S VerstovsekDepartment of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
M TalpazComprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
E RitchieDivision of Hematology and Medical Oncology, Cornell University, New York, NY, USA.
M WadleighDana-Farber Cancer Institute, Boston, MA, USA.
O OdenikeUniversity of Chicago Medical Center, Chicago, IL, USA.
C JamiesonMoores Cancer Center, University of California, San Diego, CA, USA.
B SteinFeinberg School of Medicine, Northwestern University, Chicago, IL, USA.
T UnoNS Pharma Inc., Paramus, NJ, USA.
R A MesaMayo Clinic, Scottsdale, AZ, USA.
Cornell University · USDana-Farber Cancer Institute · USMayo Clinic in Arizona · USNorthwestern University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Diego · USUniversity of Chicago Medical Center · USUniversity of Michigan–Ann Arbor · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK-signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1-2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion.

Indexed as

Molecular Targeted TherapyAdultAgedAged, 80 and overAllelesAntineoplastic AgentsBiomarkersBone MarrowFemaleFollow-Up StudiesHumansJanus Kinase 2MaleMiddle AgedNeoplasm GradingPhenotypeAntineoplastic AgentsBiomarkersJanus Kinase 2Protein Kinase Inhibitors

Identifiers

PMID27479177
PMCPMC5292677
OpenAlexW2493211728

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.