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
NCT ID: NCT03839771
Last Updated: 2024-10-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE3
968 participants
INTERVENTIONAL
2019-03-01
2034-09-19
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
NCT03173248
A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy
NCT02677922
a New Treatment of Newly Diagnosed IDH1 Mutation Acute Myeloid Leukemia
NCT07007949
Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Maintenance Monotherapy in Patients With Newly-diagnosed FMS-like Tyrosine 3 (FLT3) Kinase Receptor-mutated Acute Myeloid Leukemia.
NCT03379727
CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
NCT04493164
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A: Placebo
Cycle 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
Placebo for AG-120
250mg tablets
Placebo for AG-221
100mg tablets
Arm B: Ivosidenib (IDH1) or Enasidenib (IDH2)
Cycle 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
AG-120
250mg tablets
AG-221
100mg tablets
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AG-120
250mg tablets
Placebo for AG-120
250mg tablets
AG-221
100mg tablets
Placebo for AG-221
100mg tablets
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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:
* 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.
* Subject agrees not to participate in another interventional study while on treatment
Exclusion Criteria
* 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.
* QTc interval using Fridericia's formula (QTcF) ≥ 450 msec 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 Principal Investigator.
* Taking medications that are known to prolong the QT interval (see Appendix K), unless deemed critical and without a suitable alternative. In those cases, they may be administered, but with proper monitoring (see section 10.2, Table 13).
* 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.
* A known medical history of progressive multifocal leukoencephalopathy (PML).
* Immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or severe disseminated intravascular coagulation
* Any other medical 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)
UNKNOWN
Stichting Hemato-Oncologie voor Volwassenen Nederland
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
B.J. Wouters
Role: PRINCIPAL_INVESTIGATOR
Erasmus MC / HOVON
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
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
Countries
Review the countries where the study has at least one active or historical site.
Related Links
Access external resources that provide additional context or updates about the study.
HOVON website
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2018-000451-41
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
HO150
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.