A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy
HOVON150AML
A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy.
2 other identifiers
interventional
968
13 countries
165
Brief Summary
AML and MDS-EB2 are malignancies of the bone marrow. The standard treatment for these diseases is chemotherapy. Patients participating have a special type of this disease because the leukemia cells (blasts) have developed an error in the genetic material (DNA). This error is called an IDH1 mutation or an IDH2 mutation (a mutation is a change in the DNA), which leads to changes in specific substances in the leukemia cells. This trial will investigate whether the addition of the new drugs Ivosidenib (for patients with IDH1 mutation) or Enasidenib (for patients with IDH2 mutation) to the standard treatment of chemotherapy controle the disease more effectively and for a longer period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2019
Longer than P75 for phase_3
165 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
February 6, 2019
CompletedFirst Posted
Study publicly available on registry
February 15, 2019
CompletedStudy Start
First participant enrolled
March 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 17, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 19, 2034
October 2, 2024
September 1, 2024
8.1 years
February 6, 2019
October 1, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Event-free survival (EFS)
EFS is defined as the time from randomization to failure to achieve CR or CRi after remission induction, death after achieving CR or CRi or relapse after achieving CR or CRi, whichever occurs first. A patient is said to have failed to achieve CR or CRi after induction therapy, if his/her best response during or at completion of the induction treatment is less than CRi. Patients who achieved CR/CRi after remission induction and are not known to have relapsed or died will be censored at the date of last clinical assessment.
Approximately up to 60 months following first patient enrollment
Secondary Outcomes (11)
Overall survival (OS)
Approximately up to 84 months following first patient enrollment
Relapse-free survival (RFS) after CR/CRi
Approximately up to 60 months following first patient enrollment
Cumulative incidence of relapse (CIR) after CR/CRi
Approximately up to 60 months following first patient enrollment
Cumulative incidence of death (CID) after CR/CRi
Approximately up to 60 months following first patient enrollment
Complete remission without minimal residual disease (CRMRD-) rate after induction cycle 2
Approximately up to 60 months following first patient enrollment
- +6 more secondary outcomes
Study Arms (2)
Arm A: Placebo
PLACEBO COMPARATORCycle 1: day 1-start cycle 2 \| Cycle 2: day 1 - start consolidation treatment \| Consolidation treatment: day 1 - start maintenance \| Maintenance treatment: day 1- day 730 (2 years) \| The dosage for Placebo for AG-120 (IDH1): 500 mg dose/day The dosage for Placebo for AG-221 (IDH2): 100mg dose/day
Arm B: Ivosidenib (IDH1) or Enasidenib (IDH2)
EXPERIMENTALCycle 1: day 1-start cycle 2 \| Cycle 2: day 1 - start consolidation treatment \| Consolidation treatment: day 1 - start maintenance \| Maintenance treatment: day 1- day 730 (2 years) \| The dosage for AG-120 (IDH1): 500 mg dose/day The dosage for AG-221 (IDH2): 100mg dose/day
Interventions
Eligibility Criteria
You may qualify if:
- Age ≥18 years
- Newly diagnosed AML or MDS-EB2 defined according to WHO criteria, with a documented IDH1 or IDH2 gene mutation (as determined by the clinical trial assay) at a specific site (IDH1 R132, IDH2 R140, IDH2 R172). AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related (in which prior disease should have been documented to have existed for at least 3 months). Patients may have had previous treatment with hypomethylating agents (HMAs) for MDS. HMAs have to be stopped at least four weeks before registration
- Patients with dual mutant FLT3 and IDH1 or IDH2 mutations may be enrolled only if, for medical or other reasons, treatment with a FLT3 inhibitor is not considered.
- Considered to be eligible for intensive chemotherapy.
- ECOG/WHO performance status ≤ 2
- Adequate hepatic function as evidenced by:
- Serum total bilirubin ≤ 2.5 × upper limit of normal (ULN) unless considered due to Gilbert's disease (e.g. a mutation in UGT1A1) (only for patients in IDH2 cohort), or leukemic involvement of the liver - 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 of the liver, following written approval by the Principal Investigator.
- Adequate renal function as evidenced by creatinine clearance \> 40 mL/min based on the Cockroft-Gault formula for glomerular filtration rate (GFR).
- Able to understand and willing to sign an informed consent form (ICF).
- Written informed consent
- Female patient must either:
- o 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)
- o 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:
- +12 more criteria
You may not qualify if:
- Prior chemotherapy for AML or MDS-EB2 (with the exception of HMA). Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell \[WBC\] counts \> 30x109/L).
- Dual IDH1 and IDH2 mutations.
- Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations.
- Blast crisis after chronic myeloid leukemia (CML).
- Known allergy or suspected hypersensitivity to Ivosidenib or Enasidenib and/or any exipients.
- Taking medications with narrow therapeutic windows with potential interaction with investigational medication (see Appendix I), unless the patient can be transferred to other medications prior to enrolling or unless the medications can be properly monitored during the study.
- Taking P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) transporter-sensitive substrate medications (see Appendix J) unless the patient can be transferred to other medications within ≥ 5 half-lives prior to administration of ivosidenib or enasidenib, or unless the medications can be properly monitored during the study.
- Breast feeding at 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 \< 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 (appendix G); myocardial infarction, unstable angina and/or stroke; or left ventricular ejection fraction (LVEF) \< 40% by ultrasound or MUGA scan obtained within 28 days prior to the start of study treatment.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (181)
AU-Adelaide-FLINDERS
Adelaide, Australia
AU-Adelaide-RAH
Adelaide, Australia
AU-Brisbane-PAH
Brisbane, Australia
AU-Camperdown-RPA
Camperdown, Australia
AU-Canberra-CANBERRAHOSPITAL
Canberra, Australia
AU-Douglas-TOWNSVILLE
Douglas, Australia
AU-Hobart TAS-RHOBART
Hobart, Australia
AU-Launceston TAS-LAUNCESTON
Launceston, Australia
AU-Melbourne-ALFRED
Melbourne, Australia
AU-Melbourne-AUSTIN
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-RNSH
Sydney, Australia
AU-Sydney-SVHS
Sydney, Australia
AU-Sydney-WSAH
Sydney, Australia
AU-Waratah-CALVARYMATER
Waratah, Australia
AT-Graz-MEDUNIGRAZ
Graz, Austria
AT-Innsbruck-IMED
Innsbruck, Austria
AT-Linz-ORDENSKLINIKUM
Linz, Austria
AT-Vienna-HANUSCH
Vienna, Austria
BE-Antwerpen-ZNASTUIVENBERG
Antwerp, Belgium
BE-Brugge-AZBRUGGE
Bruges, Belgium
BE-Brussel-BORDET
Brussels, Belgium
BE-Brussel-UZBRUSSEL
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-Roeselare-AZDELTA
Roeselare, Belgium
BE-Yvoir-MONTGODINNE
Yvoir, Belgium
EE-Tartu-TARTU
Tartu, Estonia
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-Chambery-CHMETROPOLESAVOIE
Chambéry, France
FR-Le Chesnay cedex-CHVERSAILLES
Chesnay, France
FR-Clamart-HIAPERCY
Clamart, France
FR-Clermont-Ferrand-ESTAING
Clermont-Ferrand, France
FR-Créteil cedex-CHUMONDOR
Créteil, France
FR-Grenoble cedex 9-CHUGRENOBLE
Grenoble, France
FR-Lens-CHLENS
Lens, 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-Mulhouse-GHRMSA
Mulhouse, France
FR-Nantes-CHUNANTES
Nantes, France
FR-Nice-CAL
Nice, France
FR-Nice-LARCHET
Nice, France
FR-Orléans-CHORLEANS
Orléans, France
FR-Paris cedex 10-SAINTLOUIS
Paris, France
FR-Paris cedex 12-SAINTANTOINE
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-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-Bad Saarow-HELIOSBADSAAROW
Bad Saarow, Germany
DE-Berlin-CAMPUSBENFRANKLIN
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-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-Giessen-UKGM
Giessen, Germany
DE-Goch-KKLE
Goch, 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-Herne-MARIENHOSPITALHERNE
Herne, Germany
DE-Homburg-UNIKLINIKSAARLAND
Homburg, Germany
DE-Karlsruhe-KLINIKUMKARLSRUHE
Karlsruhe, Germany
DE-Lebach-CARITASKHLEBACH
Lebach, Germany
DE-Lemgo-KLINIKUMLIPPE
Lemgo, Germany
DE-Ludwigshafen-KLILU
Ludwigshafen, Germany
DE-Luedenscheid-KLINIKUMLUEDENSCHEID
Lüdenscheid, Germany
DE-Magdeburg-OVGU
Magdeburg, Germany
DE-Mainz-KLINKUNIMAINZ
Mainz, Germany
DE-Mainz-UNIMEDIZINMAINZ
Mainz, Germany
DE-Meschede-HOCHSAUERLAND
Meschede, Germany
DE-Minden-MUEHLENKREISKLINKEN
Minden, Germany
DE-München-IRZTUM
München, Germany
DE-München-MEDUNIMUNCHIN
München, Germany
DE-Offenburg-ORTENAUKLINIKUM
Offenburg, Germany
DE-Oldenburg-KLINIKUMOLDENBURG
Oldenburg, Germany
DE-Passau-KLINIKUMPASSAU
Passau, Germany
DE-Stuttgart-DIAKSTUTTGART
Stuttgart, Germany
DE-Stuttgart-KLINIKUMSTUTTGART
Stuttgart, Germany
DE-Traunstein-TSSOB
Traunstein, 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 8-STJAMES
Dublin, Ireland
IE-Dublin 9-BEAUMONT
Dublin, Ireland
IE-Galway-UHGALWAY
Galway, Ireland
LT-Vilnius-SANTA
Vilnius, Lithuania
LU-Luxembourg-CHL
Luxembourg, Luxembourg
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-Madrid-CSGREGORIOMARANON
Madrid, 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-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-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
B.J. Wouters
Erasmus MC / HOVON
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 6, 2019
First Posted
February 15, 2019
Study Start
March 1, 2019
Primary Completion (Estimated)
April 17, 2027
Study Completion (Estimated)
September 19, 2034
Last Updated
October 2, 2024
Record last verified: 2024-09
Data Sharing
- IPD Sharing
- Will not share