Evidence map›Paper›PMID 31837959›Full record

Trial reportThe Lancet. Haematology2020

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial.

Andrew M Brunner, Traci M Blonquist, Daniel J DeAngelo, Malgorzata McMasters, Geoffrey Fell, Nicole M Hermance, Eric S Winer, R Coleman Lindsley, Gabriela S Hobbs, Philip C Amrein and 35 more

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

Trial report in The Lancet. Haematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
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  8. The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024
    Review
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  13. Nuclear Aurora kinase A switches mSignal transduction and targeted therapy · 2022
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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

45 authors at 6 institutions in 1 country.

Andrew M BrunnerMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Traci M BlonquistDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Daniel J DeAngeloDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Malgorzata McMastersBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Geoffrey FellDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nicole M HermanceDepartment of Biology, Worcester Polytechnic Institute, Worcester, MA, USA.
Eric S WinerDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
R Coleman LindsleyDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Gabriela S HobbsMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Philip C AmreinMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Hanno R HockMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
David P SteensmaDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jacqueline S GarciaDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Marlise R LuskinDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Richard M StoneDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Karen K BallenDivision of Hematology-Oncology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
Jacalyn RosenblattBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
David AviganBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Myrna R NahasBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Lourdes M MendezBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Steven L McAfeeMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Jenna A MoranMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Meghan BergeronMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Julia FosterMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Christina BertoliMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Amity L ManningDepartment of Biology, Worcester Polytechnic Institute, Worcester, MA, USA.
Kristin L McGregorMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Kaitlyn M FishmanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Frank C KuoDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Michele T BaltayDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Molly MacraeMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Meghan BurkeMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Tanya BehnanMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Margaret C WeyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Tina T SomMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Aura Y RamosMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Jessica RaeMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Jennifer Lombardi StoryMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Nicole NelsonDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Emma LoganBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Christine ConnollyMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Donna S NeubergDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yi-Bin ChenMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Timothy A GraubertMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Amir T FathiMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: afathi@partners.org.
Harvard University · USMassachusetts General Hospital · USDana-Farber Cancer Institute · USBeth Israel Deaconess Medical Center · USWorcester Polytechnic Institute · USUniversity of Virginia Health System · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Targeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2017 to 2021
$10.6M
NCI NIH HHS P01 CA066996NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA206963
6 · The paper itself

Abstract

backgroundIncreased aurora A kinase (AAK) expression occurs in acute myeloid leukaemia; AAK inhibition is a promising therapeutic target in this disease. We therefore aimed to assess the activity of alisertib combined with 7 + 3 induction chemotherapy in previously untreated patients with high-risk acute myeloid leukaemia.

methodsWe did a single-arm, phase 2 trial of patients recruited from the Dana-Farber/Harvard Cancer Center in the USA. Eligible patients had previously untreated acute myeloid leukaemia, an Eastern Cooperative Oncology Group performance status of 0-2, and were at high risk of disease as defined by the presence of an adverse-risk karyotype, the presence of secondary acute myeloid leukaemia arising from previous myelodysplastic syndrome or myeloproliferative neoplasm, the presence of therapy-related acute myeloid leukaemia, or being 65 years or older. Enrolled patients received 7 + 3 induction chemotherapy of continuous infusion of cytarabine (100 mg/m

findingsBetween Dec 31, 2015, and Aug 1, 2017, we enrolled a total of 39 eligible patients. 19 (49%) of 39 patients had secondary acute myeloid leukaemia and three (8%) had therapy-related acute myeloid leukaemia. At mid-induction, 33 (85%) of 39 patients showed marrow aplasia, six (15%) received re-induction. The median follow-up was 13·7 months (IQR 12·7-14·4). Composite remission was 64% (two-stage 95% CI 48-79), with 20 (51%) of 39 patients achieving complete remission and five (13%) achieving complete remission with incomplete neutrophil or platelet count recovery. The most common grade 3 or 4 adverse events included febrile neutropenia (16 [41%] of 39), neutropenia (12 [31%]), thrombocytopenia (13 [33%]), anaemia (11 [28%]), anorexia (nine [23%]), and oral mucositis (four [10%]). No treatment-related deaths were observed.

interpretationThese results suggest that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. This study met criteria to move forward to a future randomised trial.

fundingMillennium Pharmaceuticals.

Indexed as

Induction ChemotherapyAgedAzepinesCytarabineFemaleFollow-Up StudiesHumansIdarubicinLeukemia, Myeloid, AcuteMaleMiddle AgedPyrimidinesRisk FactorsAzepinesCytarabineIdarubicinMLN 8237Pyrimidines

Identifiers

PMID31837959
PMCPMC10354959
OpenAlexW2996166666

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Registered trials

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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.