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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)

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndrome With Excess Blasts-2

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AG-120
Placebo for AG-120
AG-221
Placebo for AG-221
Sponsored by
Stichting Hemato-Oncologie voor Volwassenen Nederland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    • 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:

  • 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.
  • 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.

Sites / Locations

  • AU-Adelaide-FLINDERSRecruiting
  • AU-Adelaide-RAHRecruiting
  • AU-Brisbane-PAHRecruiting
  • AU-Camperdown-RPARecruiting
  • AU-Canberra-CANBERRAHOSPITAL
  • AU-Douglas-TOWNSVILLERecruiting
  • AU-Hobart TAS-RHOBARTRecruiting
  • AU-Launceston TAS-LAUNCESTON
  • AU-Melbourne-ALFREDRecruiting
  • AU-Melbourne-AUSTINRecruiting
  • AU-Melbourne-MONASHRecruiting
  • AU-Melbourne-RMELBOURNERecruiting
  • AU-Melbourne-SVHMRecruiting
  • AU-Perth-FSHRecruiting
  • AU-Perth-RPH
  • AU-Perth-SCGHRecruiting
  • AU-Sydney-CONCORDRecruiting
  • AU-Sydney-RNSHRecruiting
  • AU-Sydney-SVHS
  • AU-Sydney-WSAHRecruiting
  • AU-Waratah-CALVARYMATER
  • AT-Graz-MEDUNIGRAZ
  • AT-Innsbruck-IMED
  • AT-Linz-ORDENSKLINIKUM
  • AT-Vienna-HANUSCH
  • BE-Antwerpen-ZNASTUIVENBERGRecruiting
  • BE-Brugge-AZBRUGGERecruiting
  • BE-Brussel-BORDETRecruiting
  • BE-Brussel-UZBRUSSELRecruiting
  • BE-Bruxelles-STLUCRecruiting
  • BE-Gent-UZGENTRecruiting
  • BE-Haine-Saint-Paul-JOLIMONTRecruiting
  • BE-Hasselt-VIRGAJESSERecruiting
  • BE-Leuven-UZLEUVENRecruiting
  • BE-Liege-CHRCITADELLERecruiting
  • BE-Liege-CHULIEGERecruiting
  • BE-Roeselare-AZDELTARecruiting
  • BE-Yvoir-MONTGODINNERecruiting
  • EE-Tartu-TARTURecruiting
  • FI-Helsinki-HUSRecruiting
  • FI-Tampere-TAYSRecruiting
  • FR-Amiens-CHUAMIENSRecruiting
  • FR-Angers-CHUANGERSRecruiting
  • FR-Argenteuil-CHARGENTEUILRecruiting
  • FR-Bayonne-CHCOTEBASQUERecruiting
  • FR-Besançon Cedex-JEANMINJOZRecruiting
  • FR-Bobigny-AVICENNERecruiting
  • FR-Chambery-CHMETROPOLESAVOIERecruiting
  • FR-Le Chesnay cedex-CHVERSAILLESRecruiting
  • FR-Clamart-HIAPERCYRecruiting
  • FR-Clermont-Ferrand-ESTAINGRecruiting
  • FR-Créteil cedex-CHUMONDORRecruiting
  • FR-Grenoble cedex 9-CHUGRENOBLERecruiting
  • FR-Lens-CHLENSRecruiting
  • FR-Lille-CHULILLERecruiting
  • FR-Limoges-CHULIMOGES
  • FR-Lyon Pierre Benite cedex-LYONSUDRecruiting
  • FR-Lyon-LEONBERARDRecruiting
  • FR-Marseille-IPCRecruiting
  • FR-Montpellier-STELOIRecruiting
  • FR-Mulhouse-GHRMSARecruiting
  • FR-Nantes-CHUNANTESRecruiting
  • FR-Nice-CALRecruiting
  • FR-Nice-LARCHETRecruiting
  • FR-Orléans-CHORLEANSRecruiting
  • FR-Paris cedex 10-SAINTLOUISRecruiting
  • FR-Paris cedex 12-SAINTANTOINERecruiting
  • FR-Paris cedex 15-NECKERRecruiting
  • FR-Pessac Cedex-CHUBORDEAUXRecruiting
  • FR-Poitiers-CHUPOITERSRecruiting
  • FR-Reims-CHREIMSRecruiting
  • FR-Rennes cedex 9-CHURENNESRecruiting
  • FR-Rouen cedex-BECQUERELRecruiting
  • FR-Strasbourg cedex-HAUTEPIERRERecruiting
  • FR-Toulouse-CHUTOULOUSERecruiting
  • FR-Tours cedex-BRETONNEAURecruiting
  • FR-Vandoeuvre Les Nancy-CHRUNANCYRecruiting
  • FR-Villejuif-GUSTAVEROUSSYRecruiting
  • DE-Bad Saarow-HELIOSBADSAAROWRecruiting
  • DE-Berlin-CAMPUSBENFRANKLINRecruiting
  • DE-Berlin-CAMPUSVIRCHOWRecruiting
  • DE-Berlin-VIVANTESNEUKOLLNRecruiting
  • DE-Berlin-VIVANTESURBAN
  • DE-Bochum-RUBRecruiting
  • DE-Bonn-UNIBONNRecruiting
  • DE-Braunschweig-KLINIKUMBRAUNSCHWEIGRecruiting
  • DE-Bremen-KBMRecruiting
  • DE-Dortmund-JOHODORTMUNDRecruiting
  • DE-Düsseldorf-MEDUNIDUESSELDORFRecruiting
  • DE-Essen-KEMRecruiting
  • DE-Esslingen-KLINIKUMESSLINGENRecruiting
  • DE-Flensburg-MALTESERRecruiting
  • DE-Giessen-UKGM
  • DE-Goch-KKLERecruiting
  • DE-Hamburg-ASKLEPIOSSTGEORGRecruiting
  • DE-Hamburg-ASKLEPIOSRecruiting
  • DE-Hamburg-UKE
  • DE-Hamm-EVKHAMMRecruiting
  • DE-Hanau-KLINIKUMHANAU
  • DE-Hannover-MHHANNOVERRecruiting
  • DE-Hannover-SILOAHKRHRecruiting
  • DE-Herne-MARIENHOSPITALHERNERecruiting
  • DE-Homburg-UNIKLINIKSAARLANDRecruiting
  • DE-Karlsruhe-KLINIKUMKARLSRUHERecruiting
  • DE-Lebach-CARITASKHLEBACH
  • DE-Lemgo-KLINIKUMLIPPERecruiting
  • DE-Ludwigshafen-KLILURecruiting
  • DE-Luedenscheid-KLINIKUMLUEDENSCHEIDRecruiting
  • DE-Magdeburg-OVGURecruiting
  • DE-Mainz-KLINKUNIMAINZRecruiting
  • DE-Mainz-UNIMEDIZINMAINZ
  • DE-Meschede-HOCHSAUERLANDRecruiting
  • DE-Minden-MUEHLENKREISKLINKENRecruiting
  • DE-München-IRZTUMRecruiting
  • DE-München-MEDUNIMUNCHIN
  • DE-Offenburg-ORTENAUKLINIKUMRecruiting
  • DE-Oldenburg-KLINIKUMOLDENBURGRecruiting
  • DE-Passau-KLINIKUMPASSAURecruiting
  • DE-Stuttgart-DIAKSTUTTGARTRecruiting
  • DE-Stuttgart-KLINIKUMSTUTTGART
  • DE-Traunstein-TSSOBRecruiting
  • DE-Trier-MUTTERHAUS
  • DE-Tübingen-MEDUNITUEBINGENRecruiting
  • DE-Ulm-UNIKLINKULMRecruiting
  • DE-Villingen-Schwenningen-SBKVSRecruiting
  • DE-Wuppertal-HELIOSGESUNDHEIT
  • IE-Cork-CUHRecruiting
  • IE-Dublin 8-STJAMESRecruiting
  • IE-Dublin 9-BEAUMONTRecruiting
  • IE-Galway-UHGALWAY
  • LT-Vilnius-SANTARecruiting
  • LU-Luxembourg-CHL
  • NL-Amersfoort-MEANDERMCRecruiting
  • NL-Amsterdam-AMCRecruiting
  • NL-Amsterdam-OLVGRecruiting
  • NL-Amsterdam-VUMCRecruiting
  • NL-Arnhem-RIJNSTATERecruiting
  • NL-Breda-AMPHIARecruiting
  • NL-Delft-RDGGRecruiting
  • NL-Den Bosch-JBZRecruiting
  • NL-Den Haag-HAGARecruiting
  • NL-Dordrecht-ASZRecruiting
  • NL-Eindhoven-MAXIMAMCRecruiting
  • NL-Enschede-MSTRecruiting
  • NL-Groningen-UMCGRecruiting
  • NL-Leeuwarden-MCLRecruiting
  • NL-Leiden-LUMCRecruiting
  • NL-Maastricht-MUMCRecruiting
  • NL-Nieuwegein-ANTONIUSRecruiting
  • NL-Nijmegen-RADBOUDUMCRecruiting
  • NL-Rotterdam-ErasmusMCRecruiting
  • NL-Utrecht-UMCUTRECHTRecruiting
  • NL-Zwolle-ISALARecruiting
  • NO-Bergen-HELSEBERGENRecruiting
  • NO-Oslo-OSLOUHRecruiting
  • NO-Stavanger-HELSESTAVANGERRecruiting
  • NO-Tromsø-NORTHNOORWEGENRecruiting
  • NO-Trondheim-STOLAVRecruiting
  • ES-Barcelona-CLINICUB
  • ES-Barcelona-GERMANTRIALSRecruiting
  • ES-Barcelona-ICODURANREYNALS
  • ES-Barcelona-MUTUATERRASSA
  • ES-Barcelona-PARCDESALUTMAR
  • ES-Barcelona-SANTPAURecruiting
  • ES-Barcelona-VHEBRON
  • ES-Girona-ICSTRUETARecruiting
  • ES-Madrid-CSGREGORIOMARANON
  • ES-Palma-SSIBRecruiting
  • ES-Tarragona-JOAN
  • ES-Valencia-MALVARROSA
  • SE-Lund-SUHRecruiting
  • SE-Stockholm-KAROLINSKAHUDDINGERecruiting
  • SE-Uppsala-UPPSALAUHRecruiting
  • CH-Basel-USBRecruiting
  • CH-Bellinzona-IOSIRecruiting
  • CH-Bern-INSELRecruiting
  • CH-Fribourg-HFRRecruiting
  • CH-Geneve (14)-HCUGERecruiting
  • CH-Lausanne-CHUV
  • CH-Luzern-LUKSRecruiting
  • CH-St. Gallen-KSSGRecruiting
  • CH-Zürich-USZRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm A: Placebo

Arm B: Ivosidenib (IDH1) or Enasidenib (IDH2)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall survival (OS)
OS is defined as the time from date of randomization to 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.
Relapse-free survival (RFS) after CR/CRi
RFS is defined as time from the date of achievement of CR/CRi until relapse or death from any cause, whichever comes first. Patients still in first CR/CRi and alive or lost to follow up will be censored at the date of last clinical assessment.
Cumulative incidence of relapse (CIR) after CR/CRi
CIR is measured from the date of achievement of CR/CRi 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.
Cumulative incidence of death (CID) after CR/CRi
CID is measured from the date of achievement of CR/CRi 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/CRi will be counted as competing cause of failure.
Complete remission without minimal residual disease (CRMRD-) rate after induction cycle 2
CRMRD- rate is defined as the percentage of patients who achieved CR or CRi with no evidence of MRD in bone marrow
Frequency and severity of adverse events according to CTCAE version 5.0
Adverse events will be evaluated using the National Cancer Institute's Common Terminology Criteria for AEs (CTCAE) version 5.0
CR/CRi rates after induction cycle 1 and 2
CR and CRi are determined by the Investigator based on the European LeukemiaNet (ELN2017) recommended response criteria
CR/CRi rate after remission induction (i.e., CR or CRi as best response during or at completion of induction therapy)
CR+CRi rate after remission induction is defined as the percentage of patients with best response of CR or CRi during or at completion of induction therapy
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
EQ-5D-5L visual analogue scale (VAS)
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 dimension. 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'.
EORTC-QLQ-C30 global health status/QoL scale.
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). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Estimate the average of the items that contribute to the scale; this is the raw score. a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

Full Information

First Posted
February 6, 2019
Last Updated
August 31, 2021
Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators
Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)
search

1. Study Identification

Unique Protocol Identification Number
NCT03839771
Brief Title
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
Acronym
HOVON150AML
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
March 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators
Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome With Excess Blasts-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
968 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Arm B: Ivosidenib (IDH1) or Enasidenib (IDH2)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
AG-120
Other Intervention Name(s)
Ivosidenib
Intervention Description
250mg tablets
Intervention Type
Drug
Intervention Name(s)
Placebo for AG-120
Intervention Description
250mg tablets
Intervention Type
Drug
Intervention Name(s)
AG-221
Other Intervention Name(s)
Enasidenib
Intervention Description
100mg tablets
Intervention Type
Drug
Intervention Name(s)
Placebo for AG-221
Intervention Description
100mg tablets
Primary Outcome Measure Information:
Title
Event-free survival (EFS)
Description
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.
Time Frame
Approximately up to 60 months following first patient enrollment
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS is defined as the time from date of randomization to 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.
Time Frame
Approximately up to 84 months following first patient enrollment
Title
Relapse-free survival (RFS) after CR/CRi
Description
RFS is defined as time from the date of achievement of CR/CRi until relapse or death from any cause, whichever comes first. Patients still in first CR/CRi and alive or lost to follow up will be censored at the date of last clinical assessment.
Time Frame
Approximately up to 60 months following first patient enrollment
Title
Cumulative incidence of relapse (CIR) after CR/CRi
Description
CIR is measured from the date of achievement of CR/CRi 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.
Time Frame
Approximately up to 60 months following first patient enrollment
Title
Cumulative incidence of death (CID) after CR/CRi
Description
CID is measured from the date of achievement of CR/CRi 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/CRi will be counted as competing cause of failure.
Time Frame
Approximately up to 60 months following first patient enrollment
Title
Complete remission without minimal residual disease (CRMRD-) rate after induction cycle 2
Description
CRMRD- rate is defined as the percentage of patients who achieved CR or CRi with no evidence of MRD in bone marrow
Time Frame
Approximately up to 60 months following first patient enrollment
Title
Frequency and severity of adverse events according to CTCAE version 5.0
Description
Adverse events will be evaluated using the National Cancer Institute's Common Terminology Criteria for AEs (CTCAE) version 5.0
Time Frame
Continuously throughout the study, starting from informed consent until 30 days following the last administration of any study drug
Title
CR/CRi rates after induction cycle 1 and 2
Description
CR and CRi are determined by the Investigator based on the European LeukemiaNet (ELN2017) recommended response criteria
Time Frame
Approximately up to 60 months following first patient enrollment
Title
CR/CRi rate after remission induction (i.e., CR or CRi as best response during or at completion of induction therapy)
Description
CR+CRi rate after remission induction is defined as the percentage of patients with best response of CR or CRi during or at completion of induction therapy
Time Frame
Approximately up to 60 months following first patient enrollment
Title
Time to hematopoietic recovery after each chemotherapy treatment cycle
Description
Time to hematopoietic recovery is defined as the time from the start of the cycle until recovery
Time Frame
Approximately up to 60 months following first patient enrollment
Title
EQ-5D-5L visual analogue scale (VAS)
Description
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 dimension. 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'.
Time Frame
At entry, 1st day of maintenance, every 3 months during the first year of maintenance, every 6 months during the second year of maintenance until relapse or treatment discontinuation (approximately up to 84 months following first patient enrollment)
Title
EORTC-QLQ-C30 global health status/QoL scale.
Description
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). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Estimate the average of the items that contribute to the scale; this is the raw score. a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.
Time Frame
At entry, 1st day of maintenance, every 3 months during the first year of maintenance, every 6 months during the second year of maintenance until relapse or treatment discontinuation (approximately up to 84 months following first patient enrollment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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: 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: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
B.J. Wouters, Dr.
Phone
+31 10 704 15 60
Email
b.wouters@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
K. Doehner, Prof
Phone
+49 731 500 45501
Email
konstanze.doehner@uniklinik-ulm.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
B.J. Wouters
Organizational Affiliation
Erasmus MC / HOVON
Official's Role
Principal Investigator
Facility Information:
Facility Name
AU-Adelaide-FLINDERS
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Adelaide-RAH
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Brisbane-PAH
City
Brisbane
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Camperdown-RPA
City
Camperdown
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Canberra-CANBERRAHOSPITAL
City
Canberra
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
AU-Douglas-TOWNSVILLE
City
Douglas
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Hobart TAS-RHOBART
City
Hobart
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Launceston TAS-LAUNCESTON
City
Launceston
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
AU-Melbourne-ALFRED
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Melbourne-AUSTIN
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Melbourne-MONASH
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Melbourne-RMELBOURNE
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Melbourne-SVHM
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Perth-FSH
City
Perth
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Perth-RPH
City
Perth
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
AU-Perth-SCGH
City
Perth
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Sydney-CONCORD
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Sydney-RNSH
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Sydney-SVHS
City
Sydney
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
AU-Sydney-WSAH
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Name
AU-Waratah-CALVARYMATER
City
Waratah
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
AT-Graz-MEDUNIGRAZ
City
Graz
Country
Austria
Individual Site Status
Not yet recruiting
Facility Name
AT-Innsbruck-IMED
City
Innsbruck
Country
Austria
Individual Site Status
Not yet recruiting
Facility Name
AT-Linz-ORDENSKLINIKUM
City
Linz
Country
Austria
Individual Site Status
Not yet recruiting
Facility Name
AT-Vienna-HANUSCH
City
Vienna
Country
Austria
Individual Site Status
Not yet recruiting
Facility Name
BE-Antwerpen-ZNASTUIVENBERG
City
Antwerpen
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Brugge-AZBRUGGE
City
Brugge
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Brussel-BORDET
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Brussel-UZBRUSSEL
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Bruxelles-STLUC
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Gent-UZGENT
City
Gent
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Haine-Saint-Paul-JOLIMONT
City
Haine-Saint-Paul
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Hasselt-VIRGAJESSE
City
Hasselt
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Leuven-UZLEUVEN
City
Leuven
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Liege-CHRCITADELLE
City
Liège
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Liege-CHULIEGE
City
Liège
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Roeselare-AZDELTA
City
Roeselare
Country
Belgium
Individual Site Status
Recruiting
Facility Name
BE-Yvoir-MONTGODINNE
City
Yvoir
Country
Belgium
Individual Site Status
Recruiting
Facility Name
EE-Tartu-TARTU
City
Tartu
Country
Estonia
Individual Site Status
Recruiting
Facility Name
FI-Helsinki-HUS
City
Helsinki
Country
Finland
Individual Site Status
Recruiting
Facility Name
FI-Tampere-TAYS
City
Tampere
Country
Finland
Individual Site Status
Recruiting
Facility Name
FR-Amiens-CHUAMIENS
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Angers-CHUANGERS
City
Angers
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Argenteuil-CHARGENTEUIL
City
Argenteuil
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Bayonne-CHCOTEBASQUE
City
Bayonne
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Besançon Cedex-JEANMINJOZ
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Bobigny-AVICENNE
City
Bobigny
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Chambery-CHMETROPOLESAVOIE
City
Chambéry
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Le Chesnay cedex-CHVERSAILLES
City
Chesnay
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Clamart-HIAPERCY
City
Clamart
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Clermont-Ferrand-ESTAING
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Créteil cedex-CHUMONDOR
City
Créteil
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Grenoble cedex 9-CHUGRENOBLE
City
Grenoble cedex 9
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Lens-CHLENS
City
Lens
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Lille-CHULILLE
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Limoges-CHULIMOGES
City
Limoges
Country
France
Individual Site Status
Not yet recruiting
Facility Name
FR-Lyon Pierre Benite cedex-LYONSUD
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Lyon-LEONBERARD
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Marseille-IPC
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Montpellier-STELOI
City
Montpellier
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Mulhouse-GHRMSA
City
Mulhouse
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Nantes-CHUNANTES
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Nice-CAL
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Nice-LARCHET
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Orléans-CHORLEANS
City
Orléans
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Paris cedex 10-SAINTLOUIS
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Paris cedex 12-SAINTANTOINE
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Paris cedex 15-NECKER
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Pessac Cedex-CHUBORDEAUX
City
Pessac
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Poitiers-CHUPOITERS
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Reims-CHREIMS
City
Reims
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Rennes cedex 9-CHURENNES
City
Rennes
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Rouen cedex-BECQUEREL
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Strasbourg cedex-HAUTEPIERRE
City
Strasbourg
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Toulouse-CHUTOULOUSE
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Tours cedex-BRETONNEAU
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Vandoeuvre Les Nancy-CHRUNANCY
City
Vandœuvre-lès-Nancy
Country
France
Individual Site Status
Recruiting
Facility Name
FR-Villejuif-GUSTAVEROUSSY
City
Villejuif
Country
France
Individual Site Status
Recruiting
Facility Name
DE-Bad Saarow-HELIOSBADSAAROW
City
Bad Saarow
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Berlin-CAMPUSBENFRANKLIN
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Berlin-CAMPUSVIRCHOW
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Berlin-VIVANTESNEUKOLLN
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Berlin-VIVANTESURBAN
City
Berlin
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Bochum-RUB
City
Bochum
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Bonn-UNIBONN
City
Bonn
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
City
Braunschweig
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Bremen-KBM
City
Bremen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Dortmund-JOHODORTMUND
City
Dortmund
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Düsseldorf-MEDUNIDUESSELDORF
City
Düsseldorf
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Essen-KEM
City
Essen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Esslingen-KLINIKUMESSLINGEN
City
Esslingen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Flensburg-MALTESER
City
Flensburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Giessen-UKGM
City
Gießen
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Goch-KKLE
City
Goch
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Hamburg-ASKLEPIOSSTGEORG
City
Hamburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Hamburg-ASKLEPIOS
City
Hamburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Hamburg-UKE
City
Hamburg
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Hamm-EVKHAMM
City
Hamm
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Hanau-KLINIKUMHANAU
City
Hanau
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Hannover-MHHANNOVER
City
Hannover
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Hannover-SILOAHKRH
City
Hannover
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Herne-MARIENHOSPITALHERNE
City
Herne
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Homburg-UNIKLINIKSAARLAND
City
Homburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Karlsruhe-KLINIKUMKARLSRUHE
City
Karlsruhe
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Lebach-CARITASKHLEBACH
City
Lebach
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Lemgo-KLINIKUMLIPPE
City
Lemgo
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Ludwigshafen-KLILU
City
Ludwigshafen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Luedenscheid-KLINIKUMLUEDENSCHEID
City
Lüdenscheid
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Magdeburg-OVGU
City
Magdeburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Mainz-KLINKUNIMAINZ
City
Mainz
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Mainz-UNIMEDIZINMAINZ
City
Mainz
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Meschede-HOCHSAUERLAND
City
Meschede
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Minden-MUEHLENKREISKLINKEN
City
Minden
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-München-IRZTUM
City
München
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-München-MEDUNIMUNCHIN
City
München
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Offenburg-ORTENAUKLINIKUM
City
Offenburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Oldenburg-KLINIKUMOLDENBURG
City
Oldenburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Passau-KLINIKUMPASSAU
City
Passau
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Stuttgart-DIAKSTUTTGART
City
Stuttgart
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Stuttgart-KLINIKUMSTUTTGART
City
Stuttgart
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Traunstein-TSSOB
City
Traunstein
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Trier-MUTTERHAUS
City
Trier
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
DE-Tübingen-MEDUNITUEBINGEN
City
Tübingen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Ulm-UNIKLINKULM
City
Ulm
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Villingen-Schwenningen-SBKVS
City
Villingen-Schwenningen
Country
Germany
Individual Site Status
Recruiting
Facility Name
DE-Wuppertal-HELIOSGESUNDHEIT
City
Wuppertal
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
IE-Cork-CUH
City
Cork
Country
Ireland
Individual Site Status
Recruiting
Facility Name
IE-Dublin 8-STJAMES
City
Dublin
Country
Ireland
Individual Site Status
Recruiting
Facility Name
IE-Dublin 9-BEAUMONT
City
Dublin
Country
Ireland
Individual Site Status
Recruiting
Facility Name
IE-Galway-UHGALWAY
City
Galway
Country
Ireland
Individual Site Status
Not yet recruiting
Facility Name
LT-Vilnius-SANTA
City
Vilnius
Country
Lithuania
Individual Site Status
Recruiting
Facility Name
LU-Luxembourg-CHL
City
Luxembourg
Country
Luxembourg
Individual Site Status
Not yet recruiting
Facility Name
NL-Amersfoort-MEANDERMC
City
Amersfoort
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Amsterdam-AMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Amsterdam-OLVG
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Amsterdam-VUMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Arnhem-RIJNSTATE
City
Arnhem
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Breda-AMPHIA
City
Breda
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Delft-RDGG
City
Delft
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Den Bosch-JBZ
City
Den Bosch
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Den Haag-HAGA
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Dordrecht-ASZ
City
Dordrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Eindhoven-MAXIMAMC
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Enschede-MST
City
Enschede
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Groningen-UMCG
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Leeuwarden-MCL
City
Leeuwarden
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Leiden-LUMC
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Maastricht-MUMC
City
Maastricht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Nieuwegein-ANTONIUS
City
Nieuwegein
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Nijmegen-RADBOUDUMC
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Rotterdam-ErasmusMC
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Utrecht-UMCUTRECHT
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NL-Zwolle-ISALA
City
Zwolle
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
NO-Bergen-HELSEBERGEN
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Name
NO-Oslo-OSLOUH
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Name
NO-Stavanger-HELSESTAVANGER
City
Stavanger
Country
Norway
Individual Site Status
Recruiting
Facility Name
NO-Tromsø-NORTHNOORWEGEN
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Name
NO-Trondheim-STOLAV
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Name
ES-Barcelona-CLINICUB
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Barcelona-GERMANTRIALS
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
ES-Barcelona-ICODURANREYNALS
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Barcelona-MUTUATERRASSA
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Barcelona-PARCDESALUTMAR
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Barcelona-SANTPAU
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
ES-Barcelona-VHEBRON
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Girona-ICSTRUETA
City
Girona
Country
Spain
Individual Site Status
Recruiting
Facility Name
ES-Madrid-CSGREGORIOMARANON
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Palma-SSIB
City
Palma
Country
Spain
Individual Site Status
Recruiting
Facility Name
ES-Tarragona-JOAN
City
Tarragona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
ES-Valencia-MALVARROSA
City
Valencia
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
SE-Lund-SUH
City
Lund
Country
Sweden
Individual Site Status
Recruiting
Facility Name
SE-Stockholm-KAROLINSKAHUDDINGE
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Name
SE-Uppsala-UPPSALAUH
City
Uppsala
Country
Sweden
Individual Site Status
Recruiting
Facility Name
CH-Basel-USB
City
Basel
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Bellinzona-IOSI
City
Bellinzona
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Bern-INSEL
City
Bern
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Fribourg-HFR
City
Fribourg
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Geneve (14)-HCUGE
City
Geneve
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Lausanne-CHUV
City
Lausanne
Country
Switzerland
Individual Site Status
Withdrawn
Facility Name
CH-Luzern-LUKS
City
Luzern
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-St. Gallen-KSSG
City
Saint Gallen
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
CH-Zürich-USZ
City
Zürich
Country
Switzerland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.hovon.nl
Description
HOVON website

Learn more about this trial

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

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