Evidence map›Paper›PMID 28370201›Full record

ArticleAmerican journal of hematology2017

A phase 1 study of AMG 900, an orally administered pan-aurora kinase inhibitor, in adult patients with acute myeloid leukemia.

Hagop M Kantarjian, Michael W Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F Chow and 3 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of hematology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01380756 (A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia), which is not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 20% 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.

NCT01380756 phase1completednot on this map

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia

TypeinterventionalSponsorAmgenRan2011 to 2014Enrolled35ConditionsCancer, Hematologic Malignancies, Leukemia, Myeloid LeukemiaArmsArm 1- Dose Escalation, Arm 2- Dose Expansion
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
  2. Review
  3. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Aurora B kinase: a potential drug target for cancer therapy.Journal of cancer research and clinical oncology · 2021
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020
    Review
  16. Review
  17. Review
  18. Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Article
  20. Article
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

13 authors at 4 institutions in 1 country.

Hagop M KantarjianDepartment of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.ORCID http://orcid.org/0000-0002-1908-3307
Michael W SchusterMedical Hematology/Oncology Stony Brook University School of Medicine, Stony Brook, New York, USA.
Nitin JainDepartment of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.
Anjali AdvaniLeukemia Program, Cleveland Clinic, Cleveland, Ohio, USA.
Elias JabbourDepartment of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.ORCID http://orcid.org/0000-0003-4465-6119
Erick GamelinResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Erik RasmussenResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Gloria JuanResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Abraham AndersonResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Vincent F ChowResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Gregory FribergResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Florian D VoglResearch and Development, Amgen Inc., Thousand Oaks, California, USA.
Mikkael A SekeresLeukemia Program, Cleveland Clinic, Cleveland, Ohio, USA.
Amgen (United States) · USThe University of Texas MD Anderson Cancer Center · USCleveland Clinic · USStony Brook University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI REZVANI, KATY · 2003 to 2023
$43.7M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632
6 · The paper itself

Abstract

Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML . Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3 + 3 design were evaluated AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule). Thirty-five patients were enrolled at 9 different dose levels: 22 patients on the 4/10 schedule (doses from 15 to 100 mg daily), and 13 patients on the 7/7 schedule (doses from 30 to 50 mg daily). Both schedules were tolerated; nausea (31%), diarrhea (29%), febrile neutropenia (29%), and fatigue (23%) were the most common treatment-related adverse events. Three patients (9%) achieved complete response with incomplete count recovery. Patients with higher baseline expression of a set of specific pathway-related genes (BIRC5, AURKA, TTK, CDC2, and CCNB1) were more likely to respond in an exploratory biomarker analysis. AMG 900 was tolerated in a general AML population, and pathway-specific biomarkers identified a potential target population. Future research efforts will be directed toward further exploration of biomarkers of response and combination of AMG 900 with other anticancer agents.

Indexed as

Administration, OralAgedAurora KinasesBiomarkersDisease ProgressionDrug Administration ScheduleDrug MonitoringFemaleHumansLeukemia, Myeloid, AcuteMaleMiddle AgedOdds RatioPhthalazinesProtein Kinase InhibitorsRetreatmentAurora KinasesBiomarkersN-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinaminePhthalazinesProtein Kinase Inhibitors

Identifiers

PMID28370201
PMCPMC5925751
OpenAlexW2597988637

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Registered trials

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.