Evidence map›Paper›PMID 24002496›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2013

Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status.

Jorge E Cortes, Hagop Kantarjian, James M Foran, Darejan Ghirdaladze, Mamia Zodelava, Gautam Borthakur, Guy Gammon, Denise Trone, Robert C Armstrong, Joyce James and 1 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 202 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
202citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT04112589 phase1 / phase2unknown statusnot on this mapstarted 2019, after this paper: background citation

A Multicenter, Prospective, Non-randomized, Phase I-II Trial to Assess the Efficacy and Safety of the Combination of Oral Quizartinib and the FLAG-IDA Chemotherapy Regimen in First Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients

TypeinterventionalSponsorPETHEMA FoundationRan2019 to 2023Enrolled63ConditionsAcute Myeloid LeukemiaArmsQuizartinib, Fludarabine, Cytarabine, Idarubicin, glycosylated G-CSF
NCT04687761 phase1 / phase2completednot on this mapstarted 2020, after this paper: background citation

A Phase I-II, Multicentre, Open Label Clinical Trial to Assess the Safety and Tolerability of the Combination of Low-dose Cytarabine or Azacitidine, Plus Venetoclax and Quizartinib in Newly Diagnosed Acute Myeloid Leukemia Patients Aged Equal or More Than 60 Years Old Ineligible for Standard Induction Chemotherapy

TypeinterventionalSponsorPETHEMA FoundationRan2020 to 2025Enrolled113ConditionsLeukemia, Myeloid, Acute, De Novo, Age More 60yrArmsAzacitidine, Venetoclax, Quizartinib, Cytarabine
3 · Its place in the literature

Who cites it

202 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  5. Quizartinib for Newly DiagnosedJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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  7. FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with aClinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  20. Gemtuzumab Ozogamicin Reduces Relapse Risk in FLT3/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016
    Trial

142 more citing papers are in PubMed but not listed here.

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

11 authors.

Jorge E CortesJorge E. Cortes, Hagop Kantarjian, and Gautam Borthakur, the University of Texas, MD Anderson Cancer Center, Houston, TX; James M. Foran, University of Alabama at Birmingham, Birmingham, AL; Darejan Ghirdaladze, Medulla-Chemotherapy and Immunotherapy Clinic; Mamia Zodelava, Hema-Hematology and Chemotherapy Clinic, T'bilisi, GA; Guy Gammon, Denise Trone, Robert C. Armstrong, and Joyce James, Ambit Biosciences, San Diego, CA; and Mark Levis, Johns Hopkins University, Baltimore, MD.
Hagop Kantarjian
James M Foran
Darejan Ghirdaladze
Mamia Zodelava
Gautam Borthakur
Guy Gammon
Denise Trone
Robert C Armstrong
Joyce James
Mark Levis

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
Incorporating FLT3 inhibitors into AML treatment regimensR01CA128864 · NCI · JOHNS HOPKINS UNIVERSITY · PI LEVIS, MARK J · 2008 to 2012
$1.7M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632NCI NIH HHS P50 CA100632-06NCI NIH HHS R01 CA128864
6 · The paper itself

Abstract

purposeFMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. PATIENTS AND

methodsQuizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML.

resultsResponses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD-positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD-negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD-indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay.

conclusionQuizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.

Indexed as

Tandem Repeat SequencesAdultAgedAged, 80 and overBenzothiazolesElectrocardiographyFemalefms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteMaleMiddle AgedMutationPhenylurea CompoundsProtein Kinase InhibitorsRecurrenceBenzothiazolesFLT3 protein, humanfms-Like Tyrosine Kinase 3Phenylurea CompoundsProtein Kinase Inhibitorsquizartinib

Identifiers

PMID24002496
PMCPMC3804291

What OpenQuestion holds

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Read underepoch 390

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.