HOVON HO156 AML

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Main info

Identifier:
HOVON 156 AML / AMLSG 28-18
Sponsor:
HOVON
Working group party:
Leukemia
Age:
>= 18
Stage:
1st Line
Echelon:
Level C-HIC&C-SCT
Included patients:
98
(of 768)
Active sites:
87
(of 200)
95 sites are pending
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.

Timeline

Scheduled
Actual
2017
11 Sep
Opportunity
2017
31 Oct
Development
2017
20 Dec
Development
2018
28 Feb
Submission in Progress
2018
01 Apr
EC Approval
2018
30 Jun
Activated
2018
02 Aug
Submission in Progress
2019
02 Aug
EC Approval
2019
31 Oct
First Site
2019
18 Nov
Activated
2019
18 Nov
First Site
2019
30 Nov
FPI
2019
20 Dec
FPI
2022
31 Dec
Endpoint Analysis
2022
31 Dec
ClosedForInclusionScheduledStart
2032
31 Dec
CloseoutInProgressLastPtOutScheduledStart
2033
31 Dec
Archived

News

16DEC2020 Update site lab manual
We have send out the site labmanual to all active sites, this document can also be found in the study documents at the bottom of this page.

04MAR2020 IF update
The IF has been updated to add a very small update of the assessment instructions that incorrectly indicated page 1 of 2 in to the top right corner, while it only existed out of 1 page. As this update is so minor it was not send out to the sites separately.

14JAN2020 IF update
The IF has been update to add the latest version of the lab manual.

20DEC2019 First study site activation
Very first study site (NL-Rotterdam-ERASMUSMC) has been activated.

02DEC2019 IF update
The IF has been update to add the eCRF instructions as well.

27NOV2019 IF update
The IF has been updated to add the new pharmacy manual.

18NOV2019 Study activation
Study has been activated

01NOV2019 IF update
The ITF has been updated as we received a new IB for Midosaturin (v23). We have updated the IF accordingly. Please download the latest IF. Also the site document checklist has been updated as the CV of the independent physician is also needed for site activation.

30OCT2019 IF update
The IF has been updated as we received a new QP declaration and a new IB for Gilteritinib. We have updated the IF accordingly. Please download the latest IF.

12SEP2019 (Investigator File uploaded)
All Dutch sites have received by email a link to the IF that contains all documents required to receive local approval. This IF contains documents like: Protocol, ICFs (both study ICF and screenings ICF), ABR form, EC correspondence and Central EC approval form, CA approval, Patient card (which you will also receive by regular post), Patient Diaries (for both Midostaurin and Gilteritinib), eCRF instructions, SAE forms, etc.

Below - in section Downloads you can download the entire zip file as well. You can also find an excel sheet (HO156_Overview folders and files_ddMONyyyy) that lists the exact documents that are within the ZIP file and indicate the section in which they are filed. If there are updates, these will be emailed to the sites, the latest version of the ZIP file can always be downloaded below.

Flow

Flow

Details

Phase:
Prospective Phase III study
Monitoring Type:
Study Specific
Objectives:

Primary study objective

  • To compare event-free survival (EFS) between gilteritinib and midostaurin in combination with induction and consolidation therapy followed by one-year maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML), with a FLT3 gene mutation eligible for intensive chemotherapy.

Key secondary study objectives

  • To determine if treatment with gilteritinib, as compared to midostaurin, prolongs overall survival (OS) in the AML patient group.
  • To compare complete remission (CR) rate after induction therapy (i.e., CR as best response during or at completion of induction) for treatment including gilteritinib vs. midostaurin in the AML patient group.

Other secondary study objectives

  • To compare CR and CR with incomplete hematologic recovery (CRi) rates after induction cycle 1 and after induction cycle 2 for treatment including gilteritinib vs. midostaurin in the AML patient group.
  • To compare relapse-free survival (RFS), cumulative incidence of relapse (CIR) and death (CID) after CR for treatment including gilteritinib vs. midostaurin in the AML patient group.
  • To evaluate minimal residual disease (MRD) status at sequential time points throughout treatment and CRMRD- rates between treatment including gilteritinib vs. midostaurin, using molecular and/or flow cytometric techniques in the AML patient group.
  • To assess the safety and tolerability of treatment including gilteritinib vs. midostaurin in the AML patient group.
  • To assess the time to hematopoietic recovery (ANC 0.5 and 1.0 x 109/L; platelets 50 and 100 x 109/L) after each chemotherapy treatment cycle in the AML patient group.
  • To assess the percentage of patients undergoing an allogeneic stem cell transplant (allo-SCT) in the AML patient group.
  • To determine quality of life (QoL) during maintenance treatment with gilteritinib vs. midostaurin in the AML patient group.

Exporatory objectives

  • To evaluate the above mentioned endpoints (section 6.1, 6.2 and 6.3) between gilteritinib and midostaurin in combination with induction and consolidation therapy followed by oneyear maintenance therapy in subjects with Myelodysplastic Syndromes (MDS) with excess blasts-2 (EB2) with a FLT3 gene mutation eligible for intensive chemotherapy.

Eligibility

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) and/or hypomethylating agents (HMAs) for 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 sequencing for FLT3-TKD. FLT3-ITD positivity is defined as a FLT3-ITD / FLT3-WT ratio of ≥ 0.05 (5%). FLT3-TKD positivity is defined as a variant allelele frequency (VAF = FLT3 TKD / (FLT3 WT + FLT3 TKD)) ≥ 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 locally accepted standards 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 (with the exception of ESA and HMA). Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts > 30 x 109/L)
  • Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations
  • Blast crisis after CML
  • Patient requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A (Appendix I)
  • Breast feeding as of the 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 hypomagnesemia at screening (defined as values below LLN)
  • 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

Registration Details

Patients who are possibly eligible for this trial should first be screened to determine the FLT3 mutation status. This can only be done after the patient has provided a written informed consent for the screening. Screening is done through a separate screening database. There are two screening databases for this trial, one managed by HOVON and one managed by AMLSG. Each group/institute that is participating in this trial is assigned one of the two screening databases.

Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:

  • By ALEA; Use goto eCRF button > select the [Patient tab] and click the [Add new patient] button. Complete all items and click the [Submit] button
  • By faxing the completed registration/randomization CRF +31 (0)10 704 1028 Monday through Friday, from 09:00 to 17:00 CET
  • By phone +31 (0)10 704 1560 Monday through Friday, from 09:00 to 17:00 CET
Go to eCRF

Participating Sites

Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.

Site
182 results
Order by
Accrual rate
Activation date
NL-Rotterdam-ERASMUSMC
10
20 Dec 2019
DE-Ulm-UNIKLINKULM
8
21 Jul 2020
NL-Groningen-UMCG
6
16 May 2020
FR-Marseille-IPC
6
20 Nov 2020
NL-Breda-AMPHIA
5
06 Feb 2020
LT-Vilnius-SANTA
5
26 Feb 2020
NL-Nieuwegein-ANTONIUS
4
10 Feb 2020
FR-Toulouse-CHUTOULOUSE
4
09 Sep 2020
NL-Amsterdam-VUMC
3
07 Feb 2020
NO-Oslo-OSLOUH
3
22 Jul 2020
NL-Zwolle-ISALA
3
01 May 2020
FR-Nice-CAL
2
16 Sep 2020
NL-Nijmegen-RADBOUDUMC
2
26 Feb 2020
FR-Lyon Pierre Benite cedex-LYONSUD
2
15 Oct 2020
NL-Eindhoven-MAXIMAMC
2
04 Mar 2020
NL-Dordrecht-ASZ
2
27 Feb 2020
DE-Bochum-RUB
2
15 Dec 2020
CH-Zürich-USZ
2
23 Oct 2020
FR-Grenoble cedex 9-CHUGRENOBLE
2
29 Jul 2020
BE-Leuven-UZLEUVEN
2
30 Oct 2020
FR-Nantes-CHUNANTES
2
20 Jul 2020
FR-Paris cedex 10-SAINTLOUIS
2
14 Jul 2020
FR-Pessac Cedex-CHUBORDEAUX
2
21 Jul 2020
NO-Stavanger-HELSESTAVANGER
1
09 Sep 2020
FR-Le Chesnay cedex-CHVERSAILLES
1
13 Jan 2021
FR-Villejuif-GUSTAVEROUSSY
1
08 Jan 2021
FR-Nice-LARCHET
1
08 Sep 2020
FR-Limoges-CHULIMOGES
1
12 Oct 2020
FR-Vandoeuvre Les Nancy-CHRUNANCY
1
07 Aug 2020
FR-Rennes cedex 9-CHURENNES
1
17 Jul 2020
FR-Paris cedex 15-NECKER
1
04 Sep 2020
FR-Angers-CHUANGERS
1
31 Jul 2020
DE-Passau-KLINIKUMPASSAU
1
28 Jan 2021
CH-Luzern-LUKS
1
18 Jan 2021
NL-Leeuwarden-MCL
1
24 Apr 2020
NL-Arnhem-RIJNSTATE
1
10 Mar 2020
BE-Antwerpen-ZNASTUIVENBERG
1
21 Oct 2020
NL-Den Bosch-JBZ
1
04 Mar 2020
BE-Roeselare-AZDELTA
1
18 Sep 2020
NL-Maastricht-MUMC
1
25 Sep 2020
DE-Meschede-HOCHSAUERLAND
07 Oct 2020
FR-Argenteuil-CHARGENTEUIL
06 Jan 2021
FR-Bobigny-AVICENNE
09 Sep 2020
ES-Barcelona-GERMANTRIALS
ES-Palma-HSLL
FR-Strasbourg cedex-HAUTEPIERRE
02 Sep 2020
ES-Barcelona-MUTUATERRASSA
FR-Rouen cedex-BECQUEREL
05 Oct 2020
DE-Berlin-CAMPUSMITTE
DE-Oldenburg-KLINIKUMOLDENBURG
FR-Poitiers-CHUPOITERS
20 Jan 2021
ES-Palma-SSIB
DE-Karlsruhe-KLINIKUMKARLSRUHE
15 Dec 2020
DE-Luedenscheid-KLINIKUMLUEDENSCHEID
09 Feb 2021
DE-München-IRZTUM
DE-Offenburg-ORTENAUKLINIKUM
18 Nov 2020
DE-Regensburg-UKR
DE-Stuttgart-DIAKSTUTTGART
25 Feb 2021
DE-Stuttgart-KLINIKUMSTUTTGART
ES-Barcelona-PARCDESALUTMAR
ES-Barcelona-SANTPAU
ES-Barcelona-VHEBRON
ES-Girona-ICSTRUETA
ES-Malaga-HUVV
ES-Tarragona-JOAN
ES-Barcelona-CLINICUB
ES-Valencia-MALVARROSA
FR-Amiens-CHUAMIENS
24 Sep 2020
DE-Lübeck-UKSHLUBECK
DE-Hamburg-ASKLEPIOSSTGEORG
IE-Co. Limerick-UHL
DE-Darmstadt-KLINIKUMDARMSTADT
24 Feb 2021
DE-Saarbrücken-CARITASKLINIKUM
23 Feb 2021
DE-Wuppertal-HELIOSGESUNDHEIT
DE-Herne-MARIENHOSPITALHERNE
18 Feb 2021
DE-Villingen-Schwenningen-SBKVS
AU-Launceston TAS-LAUNCESTON
AU-Adelaide-FLINDERS
AU-Douglas-TOWNSVILLE
AU-Brisbane-RBWH
IE-Dublin 4-SVUH
AU-Melbourne-SVHM
AU-Waratah-CALVARYMATER
AU-Perth-FSH
AU-Perth-RPH
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
IE-Dublin 9-BEAUMONT
IE-Cork-CUH
IE-Dublin 24-TUH
IE-Dublin 7-MATER
IE-Dublin 8-STJAMES
AU-Melbourne-MONASH
IE-Galway-UHGALWAY
DE-Heilbronn-SLK
07 Jan 2021
DE-Esslingen-KLINIKUMESSLINGEN
20 Jan 2021
FR-Clamart-HIAPERCY
31 Dec 2020
FR-Lille-CHULILLE
03 Dec 2020
DE-Bremen-KBM
DE-Bad Saarow-HELIOSBADSAAROW
AU-Gosford NSW-GOSFORDHOSPITAL
AU-Geelong VIC-BARWONHEALTH
AU-Sydney-RNSH
DE-Hannover-MHHANNOVER
BE-Bruxelles-STLUC
22 Oct 2020
AU-Perth-SCGH
AU-Sydney-CONCORD
AU-Adelaide-RAH
AU-Melbourne-AUSTIN
AU-Hobart TAS-RHOBART
AU-Camperdown-RPA
AU-Brisbane-PAH
AU-Melbourne-RMELBOURNE
AU-Sydney-WSAH
BE-Liege-CHULIEGE
15 Sep 2020
NO-Trondheim-STOLAV
23 Sep 2020
ES-Barcelona-ICODURANREYNALS
ES-Madrid-CSGREGORIOMARANON
BE-Hasselt-VIRGAJESSE
SE-Lund-SUH
SE-Uppsala-UPPSALAUH
10 Sep 2020
AT-Linz-ORDENSKLINIKUM
CH-Basel-USB
03 Feb 2021
CH-Aarau-KSA
CH-Bern-INSEL
26 Oct 2020
BE-Liege-CHRCITADELLE
BE-Antwerpen Edegem-UZA
BE-Gent-UZGENT
25 Feb 2021
NL-Amsterdam-AMC
19 Jun 2020
NL-Den Haag-HAGA
30 Jul 2020
NL-Leiden-LUMC
30 Jul 2020
NL-Amersfoort-MEANDERMC
10 Mar 2020
NL-Enschede-MST
13 Jan 2021
NL-Amsterdam-OLVG
03 Feb 2020
BE-Brugge-AZBRUGGE
NL-Utrecht-UMCUTRECHT
30 Mar 2020
BE-Yvoir-MONTGODINNE
BE-Haine-Saint-Paul-JOLIMONT
28 Oct 2020
NL-Delft-RDGG
29 Jul 2020
NO-Bergen-HELSEBERGEN
16 Jun 2020
CH-Lausanne-CHUV
05 Jan 2021
CH-Geneve (14)-HCUGE
18 Jan 2021
DE-Trier-MUTTERHAUS
DE-Tübingen-MEDUNITUEBINGEN
FI-Helsinki-HUS
03 Feb 2021
DE-Homburg-UNIKLINIKSAARLAND
DE-Lemgo-KLINIKUMLIPPE
NO-Tromsø-NORTHNOORWEGEN
10 Sep 2020
SE-Stockholm-KAROLINSKAHUDDINGE
DE-Minden-MUEHLENKREISKLINKEN
BE-Brussel-BORDET
DE-Berlin-CAMPUSBENFRANKLIN
DE-Ludwigshafen-KLILU
AT-Graz-MEDUNIGRAZ
DE-Aschaffenburg-KLINIKUMAB
DE-Berlin-CAMPUSVIRCHOW
DE-Berlin-VIVANTESURBAN
DE-Berlin-VIVANTESNEUKOLLN
23 Dec 2020
DE-Dortmund-JOHODORTMUND
07 Jan 2021
DE-Düsseldorf-MEDUNIDUESSELDORF
DE-Flensburg-MALTESER
22 Dec 2020
DE-Giessen-UKGM
DE-Hannover-SILOAHKRH
DE-Hamm-EVKHAMM
DE-Hamburg-UKE
FI-Tampere-TAYS
CH-St. Gallen-KSSG
DE-Mainz-KLINKUNIMAINZ
BE-Mons-AMBROISE
06 Nov 2020
CH-Bellinzona-IOSI
03 Feb 2021
CH-Fribourg-HFR
16 Nov 2020
DE-Magdeburg-OVGU
LU-Luxembourg-CHL
AU-Canberra-CANBERRAHOSPITAL
AT-Innsbruck-IMED
AT-Vienna-HANUSCH
AU-Melbourne-ALFRED
AU-Sydney-NEPEAN
AU-Sydney-STGEORGE
DE-Bonn-UNIBONN
DE-Essen-KEM
18 Nov 2020
DE-Hamburg-ASKLEPIOS
17 Feb 2021
DE-Goch-KKLE
= Active hospitals
= Inactive hospitals

Participating Parties

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