AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 3HOVON 156 AMLNCT04027309

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

A Phase 3 study testing Gilteritinib and Midostaurin in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome With Excess Blasts-2, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 193 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gilteritinib and Midostaurin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
777 participants
Where
193 sitesin 13 countries
Study dates
20 Dec 2019to Jun 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 33Show fewer
  • 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
  • Documented surgically sterile or status posthysterectomy (at least 1 month prior to screening)
  • Or, if of childbearing potential,
  • Agree not to try to become pregnant during the study and for 6 months after the final study drug administration
  • And have a negative urine or serum pregnancy test at screening
  • And, if heterosexually active, agree to consistently use highly effective* contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after the final study drug administration.
  • Highly effective forms of birth control include:
  • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation,
  • Established intrauterine device (IUD) or intrauterine system (IUS),
  • Bilateral tubal occlusion,
  • Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.)
  • Male is sterile due to a bilateral orchiectomy.
  • Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
  • (*)List is not all inclusive. Prior to enrollment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control per the requirements of the CTFG Guidance document 'Recommendations related to contraception and pregnancy testing in clinical trials', September 2014 (and any updates thereof) during the protocol defined period.
  • Female patient must agree not to breastfeed starting at screening and throughout the study period, and for 2 months and 1 week after the final study drug administration.
  • Female patient must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • Male patient and their female partners who are of childbearing potential must be using highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and continue throughout the study period and for 4 months and 1 week after the final study drug administration.
  • Male patient must not donate sperm starting at screening and throughout the study period and for 4 months and 1 week after the final study drug administration.
  • Patient agrees not to participate in another interventional study while on treatment

Who cannot join

  • 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
Show all 24Show fewer
  • 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;
  • Unstable angina and/or stroke;
  • Left ventricular ejection fraction (LVEF) < 40% by ECHO or MUGA scan obtained within 28 days prior to the start of study treatment
  • QTc interval using Fridericia's formula (QTcF) ≥ 450 msec (average of triplicate determinations) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, family history of long QT interval syndrome). Prolonged QTc interval associated with bundle branch block or pacemaking is permitted with written approval of the (co) Principal Investigator.
  • Patient with hypokalemia and/or hypomagnesemia before registration (defined as values below LLN) Note: electrolyte suppletion is allowed to correct LLN values before registration.
  • Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs
  • Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening
  • Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation
  • Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to give informed consent or participate in the study
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Trial locations and contacts

193 sites in 13 countries.

193 sites in 13 countries

Germany54 sites

  • DE-Aschaffenburg-KLINIKUMAB

    Aschaffenburg

  • DE-Bad Saarow-HELIOSBADSAAROW

    Bad Saarow

  • DE-Berlin-CAMPUSBENFRANKLIN

    Berlin

  • DE-Berlin-CAMPUSMITTE

    Berlin

  • DE-Berlin-CAMPUSVIRCHOW

    Berlin

  • DE-Berlin-VIVANTESNEUKOLLN

    Berlin

  • DE-Berlin-VIVANTESURBAN

    Berlin

  • DE-Bochum-RUB

    Bochum

  • DE-Bonn-UNIBONN

    Bonn

  • DE-Braunschweig-KLINIKUMBRAUNSCHWEIG

    Braunschweig

  • DE-Bremen-KBM

    Bremen

  • DE-Darmstadt-KLINIKUMDARMSTADT

    Darmstadt

  • DE-Dortmund-JOHODORTMUND

    Dortmund

  • DE-Düsseldorf-MEDUNIDUESSELDORF

    Düsseldorf

  • DE-Essen-KEM

    Essen

  • DE-Esslingen-KLINIKUMESSLINGEN

    Esslingen am Neckar

  • DE-Flensburg-MALTESER

    Flensburg

  • DE-Frankfurt-KLINIKUMFRANKFURT

    Frankfurt

  • DE-Giessen-UKGM

    Giessen

  • DE-Goch-KKLE

    Goch

  • DE-Greifswald-UNIGREIFSWALD

    Greifswald

  • DE-Hamburg-ASKLEPIOSSTGEORG

    Hamburg

  • DE-Hamburg-ASKLEPIOS

    Hamburg

  • DE-Hamburg-UKE

    Hamburg

  • DE-Hamm-EVKHAMM

    Hamm

  • DE-Hanau-KLINIKUMHANAU

    Hanau

  • DE-Hannover-MHHANNOVER

    Hanover

  • DE-Hannover-SILOAHKRH

    Hanover

  • DE-Heilbronn-SLK

    Heilbronn

  • DE-Herne-MARIENHOSPITALHERNE

    Herne

  • DE-Homburg-UNIKLINIKSAARLAND

    Homburg

  • DE-Kaiserslautern-WESTPFALZ

    Kaiserslautern

  • DE-Karlsruhe-KLINIKUMKARLSRUHE

    Karlsruhe

  • DE-Lemgo-KLINIKUMLIPPE

    Lemgo

  • DE-Lübeck-UKSHLUBECK

    Lübeck

  • DE-Luedenscheid-KLINIKUMLUEDENSCHEID

    Lüdenscheid

  • DE-Ludwigshafen-KLILU

    Ludwigshafen

  • DE-Magdeburg-OVGU

    Magdeburg

  • DE-Mainz-UNIMEDIZINMAINZ

    Mainz

  • DE-Meschede-HOCHSAUERLAND

    Meschede

  • DE-Minden-MUEHLENKREISKLINKEN

    Minden

  • DE-München-IRZTUM

    München

  • DE-Offenburg-ORTENAUKLINIKUM

    Offenburg

  • DE-Oldenburg-KLINIKUMOLDENBURG

    Oldenburg

  • DE-Passau-KLINIKUMPASSAU

    Passau

  • DE-Regensburg-UKR

    Regensburg

  • DE-Saarbrücken-CARITASKLINIKUM

    Saarbrücken

  • DE-Stuttgart-DIAKSTUTTGART

    Stuttgart

  • DE-Stuttgart-KLINIKUMSTUTTGART

    Stuttgart

  • DE-Trier-MUTTERHAUS

    Trier

  • DE-Tübingen-MEDUNITUEBINGEN

    Tübingen

  • DE-Ulm-UNIKLINKULM

    Ulm

  • DE-Villingen-Schwenningen-SBKVS

    Villingen-Schwenningen

  • DE-Wuppertal-HELIOSGESUNDHEIT

    Wuppertal

Other trials in Germany

France32 sites

  • FR-Amiens-CHUAMIENS

    Amiens

  • FR-Angers-CHUANGERS

    Angers

  • FR-Argenteuil-CHARGENTEUIL

    Argenteuil

  • FR-Bayonne-CHCOTEBASQUE

    Bayonne

  • FR-Besançon Cedex-JEANMINJOZ

    Besançon

  • FR-Bobigny-AVICENNE

    Bobigny

  • FR-Le Chesnay cedex-CHVERSAILLES

    Chesnay

  • FR-Clamart-HIAPERCY

    Clamart

  • FR-Clermont-Ferrand-ESTAING

    Clermont-Ferrand

  • FR-Grenoble cedex 9-CHUGRENOBLE

    Grenoble

  • FR-Lille-CHULILLE

    Lille

  • FR-Limoges-CHULIMOGES

    Limoges

  • FR-Lyon Pierre Benite cedex-LYONSUD

    Lyon

  • FR-Lyon-LEONBERARD

    Lyon

  • FR-Marseille-IPC

    Marseille

  • FR-Montpellier-STELOI

    Montpellier

  • FR-Nantes-CHUNANTES

    Nantes

  • FR-Nice-CAL

    Nice

  • FR-Nice-LARCHET

    Nice

  • FR-Paris cedex 10-SAINTLOUIS

    Paris

  • FR-Paris cedex 15-NECKER

    Paris

  • FR-Pessac Cedex-CHUBORDEAUX

    Pessac

  • FR-Poitiers-CHUPOITERS

    Poitiers

  • FR-Reims-CHREIMS

    Reims

  • FR-Rennes cedex 9-CHURENNES

    Rennes

  • FR-Rouen cedex-BECQUEREL

    Rouen

  • FR-Saint-Priest-en-Jarez-ICLOIRE

    Saint-Priest-en-Jarez

  • FR-Strasbourg cedex-HAUTEPIERRE

    Strasbourg

  • FR-Toulouse-CHUTOULOUSE

    Toulouse

  • FR-Tours cedex-BRETONNEAU

    Tours

  • FR-Vandoeuvre Les Nancy-CHRUNANCY

    Vandœuvre-lès-Nancy

  • FR-Villejuif-GUSTAVEROUSSY

    Villejuif

Other trials in France

Australia24 sites

  • AU-Adelaide-FLINDERS

    Adelaide

  • AU-Adelaide-RAH

    Adelaide

  • AU-Brisbane-PAH

    Brisbane

  • AU-Brisbane-RBWH

    Brisbane

  • AU-Camperdown-RPA

    Camperdown

  • AU-Douglas-TOWNSVILLE

    Douglas

  • AU-Geelong VIC-BARWONHEALTH

    Geelong

  • AU-Gosford NSW-GOSFORDHOSPITAL

    Gosford

  • AU-Hobart TAS-RHOBART

    Hobart

  • AU-Melbourne-ALFRED

    Melbourne

  • AU-Melbourne-AUSTIN

    Melbourne

  • AU-Melbourne-BOXHILL

    Melbourne

  • AU-Melbourne-MONASH

    Melbourne

  • AU-Melbourne-RMELBOURNE

    Melbourne

  • AU-Melbourne-SVHM

    Melbourne

  • AU-Perth-FSH

    Perth

  • AU-Perth-RPH

    Perth

  • AU-Perth-SCGH

    Perth

  • AU-Sydney-CONCORD

    Sydney

  • AU-Sydney-NEPEAN

    Sydney

  • AU-Sydney-RNSH

    Sydney

  • AU-Sydney-WSAH

    Sydney

  • St George Hospital

    Sydney

  • AU-Waratah-CALVARYMATER

    Waratah

Other trials in Australia

Netherlands21 sites

  • NL-Den Bosch-JBZ

    's-Hertogenbosch

  • NL-Amersfoort-MEANDERMC

    Amersfoort

  • NL-Amsterdam-AMC

    Amsterdam

  • NL-Amsterdam-OLVG

    Amsterdam

  • NL-Amsterdam-VUMC

    Amsterdam

  • NL-Arnhem-RIJNSTATE

    Arnhem

  • NL-Breda-AMPHIA

    Breda

  • NL-Delft-RDGG

    Delft

  • NL-Dordrecht-ASZ

    Dordrecht

  • NL-Eindhoven-MAXIMAMC

    Eindhoven

  • NL-Enschede-MST

    Enschede

  • NL-Groningen-UMCG

    Groningen

  • NL-Leeuwarden-MCL

    Leeuwarden

  • NL-Leiden-LUMC

    Leiden

  • NL-Maastricht-MUMC

    Maastricht

  • NL-Nieuwegein-ANTONIUS

    Nieuwegein

  • NL-Nijmegen-RADBOUDUMC

    Nijmegen

  • NL-Rotterdam-ERASMUSMC

    Rotterdam

  • NL-Den Haag-HAGA

    The Hague

  • NL-Utrecht-UMCUTRECHT

    Utrecht

  • NL-Zwolle-ISALA

    Zwolle

Other trials in Netherlands

Spain14 sites

  • ES-Barcelona-CLINICUB

    Barcelona

  • ES-Barcelona-GERMANTRIALS

    Barcelona

  • ES-Barcelona-ICODURANREYNALS

    Barcelona

  • ES-Barcelona-MUTUATERRASSA

    Barcelona

  • ES-Barcelona-PARCDESALUTMAR

    Barcelona

  • ES-Barcelona-SANTPAU

    Barcelona

  • ES-Barcelona-VHEBRON

    Barcelona

  • ES-Girona-ICSTRUETA

    Girona

  • ES-Lleida-ICSVILANOVA

    Lleida

  • ES-Madrid-CSGREGORIOMARANON

    Madrid

  • ES-Palma-HSLL

    Palma

  • ES-Palma-SSIB

    Palma

  • ES-Tarragona-JOAN

    Tarragona

  • ES-Valencia-MALVARROSA

    Valencia

Other trials in Spain

Belgium13 sites

  • BE-Antwerpen-ZNASTUIVENBERG

    Antwerp

  • BE-Brugge-AZBRUGGE

    Bruges

  • BE-Brussel-BORDET

    Brussels

  • BE-Bruxelles-STLUC

    Brussels

  • BE-Gent-UZGENT

    Ghent

  • BE-Haine-Saint-Paul-JOLIMONT

    Haine-Saint-Paul

  • BE-Hasselt-VIRGAJESSE

    Hasselt

  • BE-Leuven-UZLEUVEN

    Leuven

  • BE-Liege-CHRCITADELLE

    Liège

  • BE-Liege-CHULIEGE

    Liège

  • BE-Mons-AMBROISE

    Mons

  • BE-Roeselare-AZDELTA

    Roeselare

  • BE-Yvoir-MONTGODINNE

    Yvoir

Other trials in Belgium

Switzerland10 sites

  • CH-Aarau-KSA

    Aarau

  • CH-Basel-USB

    Basel

  • CH-Bellinzona-IOSI

    Bellinzona

  • CH-Bern-INSEL

    Bern

  • CH-Fribourg-HFR

    Fribourg

  • CH-Geneve (14)-HCUGE

    Geneva

  • CH-Lausanne-CHUV

    Lausanne

  • CH-Luzern-LUKS

    Lucerne

  • CH-St. Gallen-KSSG

    Sankt Gallen

  • CH-Zürich-USZ

    Zurich

Other trials in Switzerland

Ireland8 sites

  • IE-Cork-CUH

    Cork

  • IE-Dublin 24-TUH

    Dublin

  • IE-Dublin 4-SVUH

    Dublin

  • IE-Dublin 7-MATER

    Dublin

  • IE-Dublin 8-STJAMES

    Dublin

  • IE-Dublin 9-BEAUMONT

    Dublin

  • IE-Galway-UHGALWAY

    Galway

  • IE-Co. Limerick-UHL

    Limerick

Other trials in Ireland

Austria6 sites

  • AT-Graz-MEDUNIGRAZ

    Graz

  • AT-Innsbruck-IMED

    Innsbruck

  • AT-Linz-KEPLER

    Linz

  • AT-Linz-ORDENSKLINIKUM

    Linz

  • AT-Salzburg-SALK

    Salzburg

  • AT-Vienna-HANUSCH

    Vienna

Other trials in Austria

Norway5 sites

  • NO-Bergen-HELSEBERGEN

    Bergen

  • NO-Oslo-OSLOUH

    Oslo

  • NO-Stavanger-HELSESTAVANGER

    Stavanger

  • NO-Tromsø-NORTHNOORWEGEN

    Tromsø

  • NO-Trondheim-STOLAV

    Trondheim

Other trials in Norway

Sweden3 sites

  • SE-Lund-SUH

    Lund

  • SE-Stockholm-KAROLINSKAHUDDINGE

    Stockholm

  • SE-Uppsala-UPPSALAUH

    Uppsala

Other trials in Sweden

Finland2 sites

  • FI-Helsinki-HUS

    Helsinki

  • FI-Tampere-TAYS

    Tampere

Other trials in Finland

Lithuania1 site

  • LT-Vilnius-SANTA

    Vilnius

Other trials in Lithuania

About this study

Official title: 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)

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.

Read the detailed description

AML and MDS-EB2 are malignant diseases of the bone marrow. The standard treatment for these diseases is chemotherapy. A subgroup of these diseases is characterized by a specific error in the DNA of the leukemic cells. This is the FLT3 mutation, which leads to a change of a certain protein (FLT3) on the blasts. This altered protein plays an important role in the development of leukemia and the survival of leukemic cells.

FLT3 can be inhibited by the drug midostaurin. Adding midostaurin to chemotherapy leads to better treatment results in patients with AML. Therefore, the standard treatment for AML or MDS-EB2 with a FLT3 mutation (FLT3-AML) is a combination of chemotherapy and midostaurin.

Gilteritinib is also a drug that inhibits FLT3. In laboratory studies, gilteritinib was found to be significantly more specific and potent than midostaurin in inhibiting FLT3.

Gilteritinib has subsequently been studied in patients with AML, who relapsed after previous treatment with chemotherapy. This resulted in a much larger number of complete remissions than previously seen when comparable patients were treated with midostaurin.

Being tested
Gilteritinib, Midostaurin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GilteritinibDrug

    Also called ASP2215

    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

  • MidostaurinDrug

    Also called Rydapt

    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

Study groups in NCT04027309
Study groupRoleWhat they receive
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)
Receives: Drug: Midostaurin
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)
Receives: Drug: Gilteritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Approximately up to 70 months following first patient enrolment

Secondary outcomes (14)

  1. Event-free survival (EFS)

    Event-free survival (EFS), defined as the time from randomization to failure to achieve CR after remission induction, death or relapse after achieving CR, whichever occurs first. A patient is said to have failed to achieve CR after remission induction if his/her best response during or at completion of the induction therapy is less than CR. Patients who achieved CR after remission induction and are not known to have relapsed or died will be censored at the date of last clinical assessment. CR is determined by the Investigator according to the European LeukemiaNet (ELN2017) recommended response criteria.

    Measured: Approximately up to 70 months following first patient enrolment

  2. CR rate after remission induction

    CR rate after remission induction is defined as the percentage of patients with best response of CR during or at completion of induction therapy.

    Measured: Approximately up to 70 months following first patient enrolment

  3. EFS with modified CR (mEFS)

    EFS with modified CR (mEFS) is defined similarly to EFS above. It is the time from randomization to failure to achieve CR after remission induction, death or relapse after achieving CR, whichever occurs first. However, a patient will be considered to have failed to achieve CR after remission induction if CR is not achieved within 60 days after the start of the last induction cycle. Patients who achieve CR within 60 days of the start of the last induction cycle and are not known to have relapsed or died will be censored at the date of last clinical assessment.

    Measured: Approximately up to 70 months following first patient enrolment

  4. CR and CRi rates after induction cycle 1 and after induction cycle 2

    CR and CRi are determined by the Investigator based on the European LeukemiaNet (ELN2017) recommended response criteria.

    Measured: Approximately up to 70 months following first patient enrolment

  5. Relapse-free survival (RFS) after CR

    RFS is defined as time from the date of achievement of CR as determined by the Investigator until relapse or death from any cause, whichever comes first. Patients still in first CR and alive or lost to follow up will be censored at the date of last clinical assessment.

    Measured: Approximately up to 70 months following first patient enrolment

  6. Cumulative incidence of relapse (CIR) after CR

    CIR is measured from the date of achievement of CR as determined by the Investigator until the date of relapse. Patients not known to have relapsed will be censored on the date of last clinical assessment. Patients who died without relapse will be counted as a competing cause of failure.

    Measured: Approximately up to 70 months following first patient enrolment

  7. Cumulative incidence of death (CID) after CR

    CID is measured from the date of achievement of CR as determined by the Investigator until the date of death from any cause. Patients not known to have died will be censored on the date they were last known to be alive. Patients who experienced relapse in CR will be counted as competing cause of failure.

    Measured: Approximately up to 70 months following first patient enrolment

  8. CR without minimal residual disease (CRMRD-) rate after induction cycle 2

    CRMRD- rate is defined as the percentage of patients who achieved CR as determined by the Investigator with no evidence of MRD

    Measured: Approximately up to 70 months following first patient enrolment

  9. CR or CRi without minimal residual disease (CR/CRiMRD-) rate after induction cycle 2

    CR or CRi without minimal residual disease (CR/CRiMRD-) rate after induction cycle 2, defined as the percentage of patients who achieved CR or CRi as determined by the Investigator with no evidence of MRD

    Measured: Approximately up to 70 months following first patient enrolment

  10. Frequency and severity of adverse events according to CTCAE v5.0

    Adverse events will be evaluated using the National Cancer Institute's Common Terminology Criteria for AEs (CTCAE) version 5.0

    Measured: Continuously throughout the study, starting from informed consent until 30 days following the last administration of any study drug

  11. Time to hematopoietic recovery after each chemotherapy treatment cycle

    Time to hematopoietic recovery is defined as the time from the start of the cycle until recovery

    Measured: Approximately up to 70 months following first patient enrolment

  12. Allogeneic stem cell transplantation (allo-SCT) rate

    Allo-SCT rate is defined as the percentage of patients who underwent an allo-SCT

    Measured: Approximately up to 70 months following first patient enrolment

  13. Individual domain scores and visual analogue scale (VAS) score of the European Quality of Life 5 Dimensions (EQ-5D-5L) Questionnaire

    The EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today". Each domain has 5 levels. Each level has a 1 digit number expressing the level selected for that domain. These levels are summed up and the self-rated health is recorded on a 20 cm vertical, visual analogue scale, with endpoints labelled "the best health you can imagine" and "the worst health you can imagine".

    Measured: At entry, 1st day of maintenance and every 3 months during maintenance until relapse or treatment discontinuation (approximately up to 70 months following first patient enrolment)

  14. Individual subdomain scores and the global health status/QoL scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

    The EORTC QLQ-C30 is a 30-item questionnaire that assesses 5 functional subdomains (physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning), 1 global health status, 3 symptom subdomains (fatigue, nausea and vomiting and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most of the 30 items have 4 response levels (1="not at all", 2="a little", 3="quite a bit", and 4="very much"), with 2 questions relying on a 7-point numeric rating scale from 1="very poor" to 7="excellent". Raw scores are transformed into scale scores ranging from 0 to 100, with higher scores representing better functioning/QoL or worse symptom burden.

    Measured: At entry, 1st day of maintenance and every 3 months during maintenance until relapse or treatment discontinuation (approximately up to 70 months following first patient enrolment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2019
  2. Study start20 Dec 2019
  3. Primary completionOct 2025 (estimated)
  4. Study completionJun 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
777 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04027309
Sponsor's protocol ID
HO156
Other IDs
2018-000624-33, AMLSG 28-18, Pasha, 2018
Acronym
HOVON 156 AML
Status last verified
Sep 2024
First submitted
18 Jul 2019
Last updated
17 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gilteritinib and Midostaurin in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome With Excess Blasts-2, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 193 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 193 sites in Germany, France, Australia, Netherlands, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overal survival (OS) (time frame: Approximately up to 70 months following first patient enrolment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04027309.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in