Clinical trial NCT04027309: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome With Excess Blasts-2
Lead sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor class: OTHER
Collaborators: name: Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)
name: Astellas Pharma Global Development, Inc.
First posted: 2019-07-19
Enrollment: 777
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
    * 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

Exclusion Criteria:

* 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;
  * 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

Primary outcomes:
measure: Overal survival (OS)
timeFrame: Approximately up to 70 months following first patient enrolment
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: Approximately up to 70 months following first patient enrolment
measure: CR rate after remission induction
timeFrame: Approximately up to 70 months following first patient enrolment
measure: EFS with modified CR (mEFS)
timeFrame: Approximately up to 70 months following first patient enrolment
measure: CR and CRi rates after induction cycle 1 and after induction cycle 2
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Relapse-free survival (RFS) after CR
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Cumulative incidence of relapse (CIR) after CR
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Cumulative incidence of death (CID) after CR
timeFrame: Approximately up to 70 months following first patient enrolment
measure: CR without minimal residual disease (CRMRD-) rate after induction cycle 2
timeFrame: Approximately up to 70 months following first patient enrolment
measure: CR or CRi without minimal residual disease (CR/CRiMRD-) rate after induction cycle 2
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Frequency and severity of adverse events according to CTCAE v5.0
timeFrame: Continuously throughout the study, starting from informed consent until 30 days following the last administration of any study drug
measure: Time to hematopoietic recovery after each chemotherapy treatment cycle
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Allogeneic stem cell transplantation (allo-SCT) rate
timeFrame: Approximately up to 70 months following first patient enrolment
measure: Individual domain scores and visual analogue scale (VAS) score of the European Quality of Life 5 Dimensions (EQ-5D-5L) Questionnaire
timeFrame: 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)
measure: 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)
timeFrame: 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)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: AU-Adelaide-FLINDERS
city: Adelaide
country: Australia
facility: AU-Adelaide-RAH
city: Brisbane
country: Australia
facility: AU-Brisbane-PAH
city: Brisbane
country: Australia
facility: AU-Brisbane-RBWH
city: Camperdown
country: Australia
facility: AU-Camperdown-RPA
city: Douglas
country: Australia
facility: AU-Douglas-TOWNSVILLE
city: Geelong
country: Australia
facility: AU-Geelong VIC-BARWONHEALTH
city: Gosford
country: Australia
facility: AU-Gosford NSW-GOSFORDHOSPITAL
city: Hobart
country: Australia
facility: AU-Hobart TAS-RHOBART
city: Melbourne
country: Australia
facility: AU-Melbourne-ALFRED
city: Melbourne
country: Australia
facility: AU-Melbourne-AUSTIN
city: Melbourne
country: Australia
facility: AU-Melbourne-BOXHILL
city: Melbourne
country: Australia
facility: AU-Melbourne-MONASH
city: Melbourne
country: Australia
facility: AU-Melbourne-RMELBOURNE
city: Melbourne
country: Australia
facility: AU-Melbourne-SVHM
city: Perth
country: Australia
facility: AU-Perth-FSH
city: Perth
country: Australia
facility: AU-Perth-RPH
city: Perth
country: Australia
facility: AU-Perth-SCGH
city: Sydney
country: Australia
facility: AU-Sydney-CONCORD
city: Sydney
country: Australia
facility: AU-Sydney-NEPEAN
city: Sydney
country: Australia
facility: AU-Sydney-RNSH
city: Sydney
country: Australia
facility: AU-Sydney-WSAH
city: Sydney
country: Australia
facility: St George Hospital
city: Waratah
country: Australia
facility: AU-Waratah-CALVARYMATER
city: Graz
country: Austria
facility: AT-Graz-MEDUNIGRAZ
city: Innsbruck
country: Austria
facility: AT-Innsbruck-IMED
city: Linz
country: Austria
facility: AT-Linz-KEPLER
city: Linz
country: Austria
facility: AT-Linz-ORDENSKLINIKUM
city: Salzburg
country: Austria
facility: AT-Salzburg-SALK
city: Vienna
country: Austria
facility: AT-Vienna-HANUSCH
city: Antwerpen
country: Belgium
facility: BE-Antwerpen-ZNASTUIVENBERG
city: Brugge
country: Belgium
facility: BE-Brugge-AZBRUGGE
city: Brussels
country: Belgium
facility: BE-Brussel-BORDET
city: Brussels
country: Belgium
facility: BE-Bruxelles-STLUC
city: Gent
country: Belgium
facility: BE-Gent-UZGENT
city: Haine-Saint-Paul
country: Belgium
facility: BE-Haine-Saint-Paul-JOLIMONT
city: Hasselt
country: Belgium
facility: BE-Hasselt-VIRGAJESSE
city: Leuven
country: Belgium
facility: BE-Leuven-UZLEUVEN
city: Liège
country: Belgium
facility: BE-Liege-CHRCITADELLE
city: Liège
country: Belgium
facility: BE-Liege-CHULIEGE
city: Mons
country: Belgium
facility: BE-Mons-AMBROISE
city: Roeselare
country: Belgium
facility: BE-Roeselare-AZDELTA
city: Yvoir
country: Belgium
facility: BE-Yvoir-MONTGODINNE
city: Helsinki
country: Finland
facility: FI-Helsinki-HUS
city: Tampere
country: Finland
facility: FI-Tampere-TAYS
city: Amiens
country: France
facility: FR-Amiens-CHUAMIENS
city: Angers
country: France
facility: FR-Angers-CHUANGERS
city: Argenteuil
country: France
facility: FR-Argenteuil-CHARGENTEUIL
city: Bayonne
country: France
facility: FR-Bayonne-CHCOTEBASQUE
city: Besançon
country: France
facility: FR-Besançon Cedex-JEANMINJOZ
city: Bobigny
country: France
facility: FR-Bobigny-AVICENNE
city: Chesnay
country: France
facility: FR-Le Chesnay cedex-CHVERSAILLES
city: Clamart
country: France
facility: FR-Clamart-HIAPERCY
city: Clermont-Ferrand
country: France
facility: FR-Clermont-Ferrand-ESTAING
city: Grenoble cedex 9
country: France
facility: FR-Grenoble cedex 9-CHUGRENOBLE
city: Lille
country: France
facility: FR-Lille-CHULILLE
city: Limoges
country: France
facility: FR-Limoges-CHULIMOGES
city: Lyon
country: France
facility: FR-Lyon Pierre Benite cedex-LYONSUD
city: Lyon
country: France
facility: FR-Lyon-LEONBERARD
city: Marseille
country: France
facility: FR-Marseille-IPC
city: Montpellier
country: France
facility: FR-Montpellier-STELOI
city: Nantes
country: France
facility: FR-Nantes-CHUNANTES
city: Nice
country: France
facility: FR-Nice-CAL
city: Nice
country: France
facility: FR-Nice-LARCHET
city: Paris
country: France
facility: FR-Paris cedex 10-SAINTLOUIS
city: Paris
country: France
facility: FR-Paris cedex 15-NECKER
city: Pessac
country: France
facility: FR-Pessac Cedex-CHUBORDEAUX
city: Poitiers
country: France
facility: FR-Poitiers-CHUPOITERS
city: Reims
country: France
facility: FR-Reims-CHREIMS
city: Rennes
country: France
facility: FR-Rennes cedex 9-CHURENNES
city: Rouen
country: France
facility: FR-Rouen cedex-BECQUEREL
city: Saint-Priest-en-Jarez
country: France
facility: FR-Saint-Priest-en-Jarez-ICLOIRE
city: Strasbourg
country: France
facility: FR-Strasbourg cedex-HAUTEPIERRE
city: Toulouse
country: France
facility: FR-Toulouse-CHUTOULOUSE
city: Tours
country: France
facility: FR-Tours cedex-BRETONNEAU
city: Vandœuvre-lès-Nancy
country: France
facility: FR-Vandoeuvre Les Nancy-CHRUNANCY
city: Villejuif
country: France
facility: FR-Villejuif-GUSTAVEROUSSY
city: Aschaffenburg
country: Germany
facility: DE-Aschaffenburg-KLINIKUMAB
city: Bad Saarow
country: Germany
facility: DE-Bad Saarow-HELIOSBADSAAROW
city: Berlin
country: Germany
facility: DE-Berlin-CAMPUSBENFRANKLIN
city: Berlin
country: Germany
facility: DE-Berlin-CAMPUSMITTE
city: Berlin
country: Germany
facility: DE-Berlin-CAMPUSVIRCHOW
city: Berlin
country: Germany
facility: DE-Berlin-VIVANTESNEUKOLLN
city: Berlin
country: Germany
facility: DE-Berlin-VIVANTESURBAN
city: Bochum
country: Germany
facility: DE-Bochum-RUB
city: Bonn
country: Germany
facility: DE-Bonn-UNIBONN
city: Braunschweig
country: Germany
facility: DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
city: Bremen
country: Germany
facility: DE-Bremen-KBM
city: Darmstadt
country: Germany
facility: DE-Darmstadt-KLINIKUMDARMSTADT
city: Dortmund
country: Germany
facility: DE-Dortmund-JOHODORTMUND
city: Düsseldorf
country: Germany
facility: DE-Düsseldorf-MEDUNIDUESSELDORF
city: Essen
country: Germany
facility: DE-Essen-KEM
city: Esslingen
country: Germany
facility: DE-Esslingen-KLINIKUMESSLINGEN
city: Flensburg
country: Germany
facility: DE-Flensburg-MALTESER
city: Frankfurt
country: Germany
facility: DE-Frankfurt-KLINIKUMFRANKFURT
city: Gießen
country: Germany
facility: DE-Giessen-UKGM
city: Goch
country: Germany
facility: DE-Goch-KKLE
city: Greifswald
country: Germany
facility: DE-Greifswald-UNIGREIFSWALD
city: Hamburg
country: Germany
facility: DE-Hamburg-ASKLEPIOSSTGEORG
city: Hamburg
country: Germany
facility: DE-Hamburg-ASKLEPIOS
city: Hamburg
country: Germany
facility: DE-Hamburg-UKE
city: Hamm
country: Germany
facility: DE-Hamm-EVKHAMM
city: Hanau
country: Germany
facility: DE-Hanau-KLINIKUMHANAU
city: Hannover
country: Germany
facility: DE-Hannover-MHHANNOVER
city: Hannover
country: Germany
facility: DE-Hannover-SILOAHKRH
city: Heilbronn
country: Germany
facility: DE-Heilbronn-SLK
city: Herne
country: Germany
facility: DE-Herne-MARIENHOSPITALHERNE
city: Homburg
country: Germany
facility: DE-Homburg-UNIKLINIKSAARLAND
city: Kaiserslautern
country: Germany
facility: DE-Kaiserslautern-WESTPFALZ
city: Karlsruhe
country: Germany
facility: DE-Karlsruhe-KLINIKUMKARLSRUHE
city: Lemgo
country: Germany
facility: DE-Lemgo-KLINIKUMLIPPE
city: Ludwigshafen
country: Germany
facility: DE-Ludwigshafen-KLILU
city: Lübeck
country: Germany
facility: DE-Lübeck-UKSHLUBECK
city: Lüdenscheid
country: Germany
facility: DE-Luedenscheid-KLINIKUMLUEDENSCHEID
city: Magdeburg
country: Germany
facility: DE-Magdeburg-OVGU
city: Mainz
country: Germany
facility: DE-Mainz-UNIMEDIZINMAINZ
city: Meschede
country: Germany
facility: DE-Meschede-HOCHSAUERLAND
city: Minden
country: Germany
facility: DE-Minden-MUEHLENKREISKLINKEN
city: München
country: Germany
facility: DE-München-IRZTUM
city: Offenburg
country: Germany
facility: DE-Offenburg-ORTENAUKLINIKUM
city: Oldenburg
country: Germany
facility: DE-Oldenburg-KLINIKUMOLDENBURG
city: Passau
country: Germany
facility: DE-Passau-KLINIKUMPASSAU
city: Regensburg
country: Germany
facility: DE-Regensburg-UKR
city: Saarbrücken
country: Germany
facility: DE-Saarbrücken-CARITASKLINIKUM
city: Stuttgart
country: Germany
facility: DE-Stuttgart-DIAKSTUTTGART
city: Stuttgart
country: Germany
facility: DE-Stuttgart-KLINIKUMSTUTTGART
city: Trier
country: Germany
facility: DE-Trier-MUTTERHAUS
city: Tübingen
country: Germany
facility: DE-Tübingen-MEDUNITUEBINGEN
city: Ulm
country: Germany
facility: DE-Ulm-UNIKLINKULM
city: Villingen-Schwenningen
country: Germany
facility: DE-Villingen-Schwenningen-SBKVS
city: Wuppertal
country: Germany
facility: DE-Wuppertal-HELIOSGESUNDHEIT
city: Cork
country: Ireland
facility: IE-Cork-CUH
city: Dublin
country: Ireland
facility: IE-Dublin 24-TUH
city: Dublin
country: Ireland
facility: IE-Dublin 4-SVUH
city: Dublin
country: Ireland
facility: IE-Dublin 7-MATER
city: Dublin
country: Ireland
facility: IE-Dublin 8-STJAMES
city: Dublin
country: Ireland
facility: IE-Dublin 9-BEAUMONT
city: Galway
country: Ireland
facility: IE-Galway-UHGALWAY
city: Limerick
country: Ireland
facility: IE-Co. Limerick-UHL
city: Vilnius
country: Lithuania
facility: LT-Vilnius-SANTA
city: Amersfoort
country: Netherlands
facility: NL-Amersfoort-MEANDERMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-AMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-OLVG
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-VUMC
city: Arnhem
country: Netherlands
facility: NL-Arnhem-RIJNSTATE
city: Breda
country: Netherlands
facility: NL-Breda-AMPHIA
city: Delft
country: Netherlands
facility: NL-Delft-RDGG
city: Den Bosch
country: Netherlands
facility: NL-Den Bosch-JBZ
city: Den Haag
country: Netherlands
facility: NL-Den Haag-HAGA
city: Dordrecht
country: Netherlands
facility: NL-Dordrecht-ASZ
city: Eindhoven
country: Netherlands
facility: NL-Eindhoven-MAXIMAMC
city: Enschede
country: Netherlands
facility: NL-Enschede-MST
city: Groningen
country: Netherlands
facility: NL-Groningen-UMCG
city: Leeuwarden
country: Netherlands
facility: NL-Leeuwarden-MCL
city: Leiden
country: Netherlands
facility: NL-Leiden-LUMC
city: Maastricht
country: Netherlands
facility: NL-Maastricht-MUMC
city: Nieuwegein
country: Netherlands
facility: NL-Nieuwegein-ANTONIUS
city: Nijmegen
country: Netherlands
facility: NL-Nijmegen-RADBOUDUMC
city: Rotterdam
country: Netherlands
facility: NL-Rotterdam-ERASMUSMC
city: Utrecht
country: Netherlands
facility: NL-Utrecht-UMCUTRECHT
city: Zwolle
country: Netherlands
facility: NL-Zwolle-ISALA
city: Bergen
country: Norway
facility: NO-Bergen-HELSEBERGEN
city: Oslo
country: Norway
facility: NO-Oslo-OSLOUH
city: Stavanger
country: Norway
facility: NO-Stavanger-HELSESTAVANGER
city: Tromsø
country: Norway
facility: NO-Tromsø-NORTHNOORWEGEN
city: Trondheim
country: Norway
facility: NO-Trondheim-STOLAV
city: Barcelona
country: Spain
facility: ES-Barcelona-CLINICUB
city: Barcelona
country: Spain
facility: ES-Barcelona-GERMANTRIALS
city: Barcelona
country: Spain
facility: ES-Barcelona-ICODURANREYNALS
city: Barcelona
country: Spain
facility: ES-Barcelona-MUTUATERRASSA
city: Barcelona
country: Spain
facility: ES-Barcelona-PARCDESALUTMAR
city: Barcelona
country: Spain
facility: ES-Barcelona-SANTPAU
city: Barcelona
country: Spain
facility: ES-Barcelona-VHEBRON
city: Girona
country: Spain
facility: ES-Girona-ICSTRUETA
city: Lleida
country: Spain
facility: ES-Lleida-ICSVILANOVA
city: Madrid
country: Spain
facility: ES-Madrid-CSGREGORIOMARANON
city: Palma
country: Spain
facility: ES-Palma-HSLL
city: Palma
country: Spain
facility: ES-Palma-SSIB
city: Tarragona
country: Spain
facility: ES-Tarragona-JOAN
city: Valencia
country: Spain
facility: ES-Valencia-MALVARROSA
city: Lund
country: Sweden
facility: SE-Lund-SUH
city: Stockholm
country: Sweden
facility: SE-Stockholm-KAROLINSKAHUDDINGE
city: Uppsala
country: Sweden
facility: SE-Uppsala-UPPSALAUH
city: Aarau
country: Switzerland
facility: CH-Aarau-KSA
city: Basel
country: Switzerland
facility: CH-Basel-USB
city: Bellinzona
country: Switzerland
facility: CH-Bellinzona-IOSI
city: Bern
country: Switzerland
facility: CH-Bern-INSEL
city: Fribourg
country: Switzerland
facility: CH-Fribourg-HFR
city: Geneve
country: Switzerland
facility: CH-Geneve (14)-HCUGE
city: Lausanne
country: Switzerland
facility: CH-Lausanne-CHUV
city: Luzern
country: Switzerland
facility: CH-Luzern-LUKS
city: Saint Gallen
country: Switzerland
facility: CH-St. Gallen-KSSG
city: Zürich
country: Switzerland
facility: CH-Zürich-USZ
Study officials:
affiliation: Erasmus MC / HOVON
name: M. Raaijmakers, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: