A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy
HOVON 156 AML
A Phase 3, Multicenter, Open-label, Randomized, Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes With Excess Blasts-2 (MDS-EB2) With FLT3 Mutations Eligible for Intensive Chemotherapy (HOVON 156 AML / AMLSG 28-18)
4 other identifiers
interventional
777
12 countries
169
Brief Summary
Activating mutations in the fms like tyrosine kinase 3 (FLT3) gene are observed in approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML). Addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy prolongs event-free survival (EFS) and overall survival (OS) in patients with a FLT3 mutation. Gilteritinib is a more potent and more specific inhibitor of mutant FLT3 in comparison to midostaurin and has shown promising clinical activity in AML.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2019
Longer than P75 for phase_3
169 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 18, 2019
CompletedFirst Posted
Study publicly available on registry
July 19, 2019
CompletedStudy Start
First participant enrolled
December 20, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2033
ExpectedDecember 17, 2024
September 1, 2024
5.8 years
July 18, 2019
December 12, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Overal survival (OS)
Overall survival (OS), defined as the time from date of randomization to the date of death due to any cause. Patients still alive or lost to follow up will be censored at the time they were last known to be alive.
Approximately up to 70 months following first patient enrolment
Secondary Outcomes (14)
Event-free survival (EFS)
Approximately up to 70 months following first patient enrolment
CR rate after remission induction
Approximately up to 70 months following first patient enrolment
EFS with modified CR (mEFS)
Approximately up to 70 months following first patient enrolment
CR and CRi rates after induction cycle 1 and after induction cycle 2
Approximately up to 70 months following first patient enrolment
Relapse-free survival (RFS) after CR
Approximately up to 70 months following first patient enrolment
- +9 more secondary outcomes
Study Arms (2)
Arm A (Midostaurin)
ACTIVE COMPARATORMidostaurin (50 mg BID PO) - Cycle 1 (day 8-21), Cycle 2 (day 8-21), Consolidation (only during chemo consolidation (day 8-21 - with max of 3 cycles), Maintenance (day 1-365)
Arm B (Gilteritinib)
EXPERIMENTALGilteritinib (120 mg QD PO) - Cycle 1 (day 8-21), Cycle 2 (day 8-21), Consolidation (only during chemo consolidation (day 8-21 - with max of 3 cycles), Maintenance (day 1-365)
Interventions
Patients with a FLT3 mutation w ill be randomized to receive either the investigational drug gilteritinib or midostaurin given sequentially to standard induction and consolidation chemotherapy. After completing induction and consolidation treatment, patients who achieve CR/CRi/MLFS will receive maintenance therapy with gilteritinib or midostaurin
Patients with a FLT3 mutation w ill be randomized to receive either the investigational drug gilteritinib or midostaurin given sequentially to standard induction and consolidation chemotherapy. After completing induction and consolidation treatment, patients who achieve CR/CRi/MLFS will receive maintenance therapy with gilteritinib or midostaurin
Eligibility Criteria
You may qualify if:
- Age ≥18 years
- Newly diagnosed AML or MDS with excess of blasts-2 (EB2) defined according to WHO criteria (appendix A), with centrally documented FLT3 gene mutation (either TKD or ITD or both). AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related. Patients may have had previous treatment with erythropoiesis stimulating agents (ESA) or hypomethylating agents (HMAs) for an antecedent phase of MDS. ESA and HMAs have to be stopped at least four weeks before registration.
- FLT3 mutation as assessed by DNA fragment analysis PCR for FLT3-ITD and FLT3-TKD mutation. Positivity is defined as a FLT3-ITD or FLT3-TKD / FLT3-WT ratio of ≥ 0.05 (5%).
- Considered to be eligible for intensive chemotherapy
- Patient is suitable for oral administration of study drug
- WHO/ECOG performance status ≤ 2
- Adequate hepatic function as evidenced by
- Serum total bilirubin ≤ 2.5 × upper limit of normal (ULN) unless considered due to leukemic involvement following written approval by the (co) Principal Investigator
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement following written approval by the (co) Principal Investigator
- Adequate renal function as defined by creatinine clearance \> 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR)
- Written informed consent
- Patient is capable of giving informed consent
- Female patient must either:
- Be of nonchildbearing potential:
- Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
- +18 more criteria
You may not qualify if:
- Prior chemotherapy for AML or MDS-EB2, including prior treatment with hypomethylating agents. Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell \[WBC\] counts \> 30 x 10\^9/L)
- Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations
- Blast crisis after CML
- Known or suspected hypersensitivity to midostaurin or gilteritinib and/or any excipients
- Patient requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A
- Breast feeding at start of study treatment
- Active infection, including hepatitis B or C or HIV infection that is uncontrolled at randomization. An infection controlled with an approved or closely monitored antibiotic/antiviral/antifungal treatment is allowed.
- Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin;
- Carcinoma in situ of the cervix;
- Carcinoma in situ of the breast;
- Incidental histologic finding of prostate cancer
- Significant active cardiac disease within 6 months prior to the start of study treatment, including:
- New York Heart Association (NYHA) Class III or IV congestive heart failure;
- Myocardial infarction;
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (193)
AU-Adelaide-FLINDERS
Adelaide, Australia
AU-Adelaide-RAH
Adelaide, Australia
AU-Brisbane-PAH
Brisbane, Australia
AU-Brisbane-RBWH
Brisbane, Australia
AU-Camperdown-RPA
Camperdown, Australia
AU-Douglas-TOWNSVILLE
Douglas, Australia
AU-Geelong VIC-BARWONHEALTH
Geelong, Australia
AU-Gosford NSW-GOSFORDHOSPITAL
Gosford, Australia
AU-Hobart TAS-RHOBART
Hobart, Australia
AU-Melbourne-ALFRED
Melbourne, Australia
AU-Melbourne-AUSTIN
Melbourne, Australia
AU-Melbourne-BOXHILL
Melbourne, Australia
AU-Melbourne-MONASH
Melbourne, Australia
AU-Melbourne-RMELBOURNE
Melbourne, Australia
AU-Melbourne-SVHM
Melbourne, Australia
AU-Perth-FSH
Perth, Australia
AU-Perth-RPH
Perth, Australia
AU-Perth-SCGH
Perth, Australia
AU-Sydney-CONCORD
Sydney, Australia
AU-Sydney-NEPEAN
Sydney, Australia
AU-Sydney-RNSH
Sydney, Australia
AU-Sydney-WSAH
Sydney, Australia
St George Hospital
Sydney, Australia
AU-Waratah-CALVARYMATER
Waratah, Australia
AT-Graz-MEDUNIGRAZ
Graz, Austria
AT-Innsbruck-IMED
Innsbruck, Austria
AT-Linz-KEPLER
Linz, Austria
AT-Linz-ORDENSKLINIKUM
Linz, Austria
AT-Salzburg-SALK
Salzburg, Austria
AT-Vienna-HANUSCH
Vienna, Austria
BE-Antwerpen-ZNASTUIVENBERG
Antwerp, Belgium
BE-Brugge-AZBRUGGE
Bruges, Belgium
BE-Brussel-BORDET
Brussels, Belgium
BE-Bruxelles-STLUC
Brussels, Belgium
BE-Gent-UZGENT
Ghent, Belgium
BE-Haine-Saint-Paul-JOLIMONT
Haine-Saint-Paul, Belgium
BE-Hasselt-VIRGAJESSE
Hasselt, Belgium
BE-Leuven-UZLEUVEN
Leuven, Belgium
BE-Liege-CHRCITADELLE
Liège, Belgium
BE-Liege-CHULIEGE
Liège, Belgium
BE-Mons-AMBROISE
Mons, Belgium
BE-Roeselare-AZDELTA
Roeselare, Belgium
BE-Yvoir-MONTGODINNE
Yvoir, Belgium
FI-Helsinki-HUS
Helsinki, Finland
FI-Tampere-TAYS
Tampere, Finland
FR-Amiens-CHUAMIENS
Amiens, France
FR-Angers-CHUANGERS
Angers, France
FR-Argenteuil-CHARGENTEUIL
Argenteuil, France
FR-Bayonne-CHCOTEBASQUE
Bayonne, France
FR-Besançon Cedex-JEANMINJOZ
Besançon, France
FR-Bobigny-AVICENNE
Bobigny, France
FR-Le Chesnay cedex-CHVERSAILLES
Chesnay, France
FR-Clamart-HIAPERCY
Clamart, France
FR-Clermont-Ferrand-ESTAING
Clermont-Ferrand, France
FR-Grenoble cedex 9-CHUGRENOBLE
Grenoble, France
FR-Lille-CHULILLE
Lille, France
FR-Limoges-CHULIMOGES
Limoges, France
FR-Lyon Pierre Benite cedex-LYONSUD
Lyon, France
FR-Lyon-LEONBERARD
Lyon, France
FR-Marseille-IPC
Marseille, France
FR-Montpellier-STELOI
Montpellier, France
FR-Nantes-CHUNANTES
Nantes, France
FR-Nice-CAL
Nice, France
FR-Nice-LARCHET
Nice, France
FR-Paris cedex 10-SAINTLOUIS
Paris, France
FR-Paris cedex 15-NECKER
Paris, France
FR-Pessac Cedex-CHUBORDEAUX
Pessac, France
FR-Poitiers-CHUPOITERS
Poitiers, France
FR-Reims-CHREIMS
Reims, France
FR-Rennes cedex 9-CHURENNES
Rennes, France
FR-Rouen cedex-BECQUEREL
Rouen, France
FR-Saint-Priest-en-Jarez-ICLOIRE
Saint-Priest-en-Jarez, France
FR-Strasbourg cedex-HAUTEPIERRE
Strasbourg, France
FR-Toulouse-CHUTOULOUSE
Toulouse, France
FR-Tours cedex-BRETONNEAU
Tours, France
FR-Vandoeuvre Les Nancy-CHRUNANCY
Vandœuvre-lès-Nancy, France
FR-Villejuif-GUSTAVEROUSSY
Villejuif, France
DE-Aschaffenburg-KLINIKUMAB
Aschaffenburg, Germany
DE-Bad Saarow-HELIOSBADSAAROW
Bad Saarow, Germany
DE-Berlin-CAMPUSBENFRANKLIN
Berlin, Germany
DE-Berlin-CAMPUSMITTE
Berlin, Germany
DE-Berlin-CAMPUSVIRCHOW
Berlin, Germany
DE-Berlin-VIVANTESNEUKOLLN
Berlin, Germany
DE-Berlin-VIVANTESURBAN
Berlin, Germany
DE-Bochum-RUB
Bochum, Germany
DE-Bonn-UNIBONN
Bonn, Germany
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
Braunschweig, Germany
DE-Bremen-KBM
Bremen, Germany
DE-Darmstadt-KLINIKUMDARMSTADT
Darmstadt, Germany
DE-Dortmund-JOHODORTMUND
Dortmund, Germany
DE-Düsseldorf-MEDUNIDUESSELDORF
Düsseldorf, Germany
DE-Essen-KEM
Essen, Germany
DE-Esslingen-KLINIKUMESSLINGEN
Esslingen am Neckar, Germany
DE-Flensburg-MALTESER
Flensburg, Germany
DE-Frankfurt-KLINIKUMFRANKFURT
Frankfurt, Germany
DE-Giessen-UKGM
Giessen, Germany
DE-Goch-KKLE
Goch, Germany
DE-Greifswald-UNIGREIFSWALD
Greifswald, Germany
DE-Hamburg-ASKLEPIOSSTGEORG
Hamburg, Germany
DE-Hamburg-ASKLEPIOS
Hamburg, Germany
DE-Hamburg-UKE
Hamburg, Germany
DE-Hamm-EVKHAMM
Hamm, Germany
DE-Hanau-KLINIKUMHANAU
Hanau, Germany
DE-Hannover-MHHANNOVER
Hanover, Germany
DE-Hannover-SILOAHKRH
Hanover, Germany
DE-Heilbronn-SLK
Heilbronn, Germany
DE-Herne-MARIENHOSPITALHERNE
Herne, Germany
DE-Homburg-UNIKLINIKSAARLAND
Homburg, Germany
DE-Kaiserslautern-WESTPFALZ
Kaiserslautern, Germany
DE-Karlsruhe-KLINIKUMKARLSRUHE
Karlsruhe, Germany
DE-Lemgo-KLINIKUMLIPPE
Lemgo, Germany
DE-Ludwigshafen-KLILU
Ludwigshafen, Germany
DE-Lübeck-UKSHLUBECK
Lübeck, Germany
DE-Luedenscheid-KLINIKUMLUEDENSCHEID
Lüdenscheid, Germany
DE-Magdeburg-OVGU
Magdeburg, Germany
DE-Mainz-UNIMEDIZINMAINZ
Mainz, Germany
DE-Meschede-HOCHSAUERLAND
Meschede, Germany
DE-Minden-MUEHLENKREISKLINKEN
Minden, Germany
DE-München-IRZTUM
München, Germany
DE-Offenburg-ORTENAUKLINIKUM
Offenburg, Germany
DE-Oldenburg-KLINIKUMOLDENBURG
Oldenburg, Germany
DE-Passau-KLINIKUMPASSAU
Passau, Germany
DE-Regensburg-UKR
Regensburg, Germany
DE-Saarbrücken-CARITASKLINIKUM
Saarbrücken, Germany
DE-Stuttgart-DIAKSTUTTGART
Stuttgart, Germany
DE-Stuttgart-KLINIKUMSTUTTGART
Stuttgart, Germany
DE-Trier-MUTTERHAUS
Trier, Germany
DE-Tübingen-MEDUNITUEBINGEN
Tübingen, Germany
DE-Ulm-UNIKLINKULM
Ulm, Germany
DE-Villingen-Schwenningen-SBKVS
Villingen-Schwenningen, Germany
DE-Wuppertal-HELIOSGESUNDHEIT
Wuppertal, Germany
IE-Cork-CUH
Cork, Ireland
IE-Dublin 24-TUH
Dublin, Ireland
IE-Dublin 4-SVUH
Dublin, Ireland
IE-Dublin 7-MATER
Dublin, Ireland
IE-Dublin 8-STJAMES
Dublin, Ireland
IE-Dublin 9-BEAUMONT
Dublin, Ireland
IE-Galway-UHGALWAY
Galway, Ireland
IE-Co. Limerick-UHL
Limerick, Ireland
LT-Vilnius-SANTA
Vilnius, Lithuania
NL-Den Bosch-JBZ
's-Hertogenbosch, Netherlands
NL-Amersfoort-MEANDERMC
Amersfoort, Netherlands
NL-Amsterdam-AMC
Amsterdam, Netherlands
NL-Amsterdam-OLVG
Amsterdam, Netherlands
NL-Amsterdam-VUMC
Amsterdam, Netherlands
NL-Arnhem-RIJNSTATE
Arnhem, Netherlands
NL-Breda-AMPHIA
Breda, Netherlands
NL-Delft-RDGG
Delft, Netherlands
NL-Dordrecht-ASZ
Dordrecht, Netherlands
NL-Eindhoven-MAXIMAMC
Eindhoven, Netherlands
NL-Enschede-MST
Enschede, Netherlands
NL-Groningen-UMCG
Groningen, Netherlands
NL-Leeuwarden-MCL
Leeuwarden, Netherlands
NL-Leiden-LUMC
Leiden, Netherlands
NL-Maastricht-MUMC
Maastricht, Netherlands
NL-Nieuwegein-ANTONIUS
Nieuwegein, Netherlands
NL-Nijmegen-RADBOUDUMC
Nijmegen, Netherlands
NL-Rotterdam-ERASMUSMC
Rotterdam, Netherlands
NL-Den Haag-HAGA
The Hague, Netherlands
NL-Utrecht-UMCUTRECHT
Utrecht, Netherlands
NL-Zwolle-ISALA
Zwolle, Netherlands
NO-Bergen-HELSEBERGEN
Bergen, Norway
NO-Oslo-OSLOUH
Oslo, Norway
NO-Stavanger-HELSESTAVANGER
Stavanger, Norway
NO-Tromsø-NORTHNOORWEGEN
Tromsø, Norway
NO-Trondheim-STOLAV
Trondheim, Norway
ES-Barcelona-CLINICUB
Barcelona, Spain
ES-Barcelona-GERMANTRIALS
Barcelona, Spain
ES-Barcelona-ICODURANREYNALS
Barcelona, Spain
ES-Barcelona-MUTUATERRASSA
Barcelona, Spain
ES-Barcelona-PARCDESALUTMAR
Barcelona, Spain
ES-Barcelona-SANTPAU
Barcelona, Spain
ES-Barcelona-VHEBRON
Barcelona, Spain
ES-Girona-ICSTRUETA
Girona, Spain
ES-Lleida-ICSVILANOVA
Lleida, Spain
ES-Madrid-CSGREGORIOMARANON
Madrid, Spain
ES-Palma-HSLL
Palma, Spain
ES-Palma-SSIB
Palma, Spain
ES-Tarragona-JOAN
Tarragona, Spain
ES-Valencia-MALVARROSA
Valencia, Spain
SE-Lund-SUH
Lund, Sweden
SE-Stockholm-KAROLINSKAHUDDINGE
Stockholm, Sweden
SE-Uppsala-UPPSALAUH
Uppsala, Sweden
CH-Aarau-KSA
Aarau, Switzerland
CH-Basel-USB
Basel, Switzerland
CH-Bellinzona-IOSI
Bellinzona, Switzerland
CH-Bern-INSEL
Bern, Switzerland
CH-Fribourg-HFR
Fribourg, Switzerland
CH-Geneve (14)-HCUGE
Geneva, Switzerland
CH-Lausanne-CHUV
Lausanne, Switzerland
CH-Luzern-LUKS
Lucerne, Switzerland
CH-St. Gallen-KSSG
Sankt Gallen, Switzerland
CH-Zürich-USZ
Zurich, Switzerland
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
M. Raaijmakers, Prof. Dr.
Erasmus MC / HOVON
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 18, 2019
First Posted
July 19, 2019
Study Start
December 20, 2019
Primary Completion
October 1, 2025
Study Completion (Estimated)
June 1, 2033
Last Updated
December 17, 2024
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will not share