Ivosidenib and Azacitidine With or Without Venetoclax in Adult Patients With Newly Diagnosed IDH1-Mutated AML or MDS/AML Considered Ineligible for Intensive Chemotherapy
EVOLVE 1
2 other identifiers
interventional
227
15 countries
114
Brief Summary
The standard treatment for patients with acute myeloid leukemia (AML) with an abnormality in the IDH1 gene, who are not eligible for intensive chemotherapy, is a combination of ivosidenib and azacitidine. In this study it is investigated whether adding venetoclax to the standard treatment can improve the outcome of the treatment of this specific form of AML. The safety is investigated and how well it works. In order to properly assess the value of venetoclax, the effect of venetoclax is compared with the effect of a placebo. A placebo is a product without an active ingredient, a 'fake medicinal product'.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Aug 2025
Typical duration for phase_3
114 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 19, 2025
CompletedFirst Posted
Study publicly available on registry
July 20, 2025
CompletedStudy Start
First participant enrolled
August 5, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2029
August 19, 2025
August 1, 2025
3.3 years
June 19, 2025
August 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-free survival (EFS) in patients with newly diagnosed IDH1-mutated AML ineligible for intensive chemotherapy
Event-free survival (EFS) in patients with newly diagnosed IDH1-mutated AML ineligible for intensive chemotherapy, measured from the date of randomization to the date of treatment failure, hematologic relapse from CR/CRh or death from any cause, whichever occurs first. Treatment failure is defined as lack of obtaining either CR or CRh by week 24. Patients evaluable for response but not achieving CR or CRh by week 24 will be considered a treatment failure at day 1 post randomization to avoid ambiguities of variable or prolonged periods without response. Patients who die before week 24 without response assessments will also be considered treatment failures at day 1 post randomization. Patients who are alive but not evaluable for response will be censored at day 1 post randomization. Patients who achieved CR or CRh by week 24 and are not known to have morphologic relapse or died will be censored at the date of the last clinical assessment.
12 months after inclusion of last AML patient
Secondary Outcomes (8)
Overall survival (OS) in patients with newly diagnosed IDH1-mutated AML
12 months after inclusion of last AML patient
Rate of CR/CRh in patients with newly diagnosed IDH1-mutated AML
12 months after inclusion of last AML patient
Rate of CR in patients with newly diagnosed IDH1-mutated AML
12 months after inclusion of last AML patient
Rate of CR/CRi in patients with newly diagnosed IDH1-mutated AML
12 months after inclusion of last AML patient
Rates of CR, CR/CRh and CR/CRi without measurable residual disease as assessed by multicolor flow cytometry
12 months after inclusion of last AML patient
- +3 more secondary outcomes
Study Arms (2)
Placebo comparator: Venetoclax-placebo
PLACEBO COMPARATORday 1-28 Placebo Treatment will be on a continuous 28-day cycle schedule continued until disease relapse, disease progression, development of unacceptable toxicity, death, withdrawal of subject or other protocol defined criteria for discontinuation (which ever comes first)
Experimental: Venetoclax
EXPERIMENTALday 1-28 Venetoclax Treatment will be on a continuous 28-day cycle schedule continued until disease relapse, disease progression, development of unacceptable toxicity, death, withdrawal of subject or other protocol defined criteria for discontinuation (which ever comes first)
Interventions
Eligibility Criteria
You may qualify if:
- Central confirmation of IDH1 mutation in one of the dedicated central genetic laboratories.
- Age ≥ 18 years, no upper age limit.
- Patient is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:
- older than or equal to 75 years of age ineligible for intensive chemotherapy per physician's discretion (with an ECOG performance status 0-2; Appendix C).
- years: patient is not eligible for standard chemotherapy because of any of the following co-morbidities: o ECOG performance status 2 or 3 (Appendix C). o Cardiac history of chronic heart failure requiring treatment; or with an ejection fraction ≤50%; or chronic stable angina.
- DLCO ≤ 65% or FEV1 ≤ 65%.
- Creatinine clearance ≥ 30 mL/min to \<45 ml/min calculated by the Cockcroft Gault formula.
- Moderate hepatic impairment with total bilirubin \> 1.5 to \< 3.0 x upper limit of normal (ULN).
- Any other comorbidity that the local physician assesses to be incompatible with intensive chemotherapy. If a patient meets this criterion, sponsor must be informed via HO173@erasmusmc.nl
- Patient must have a projected life expectancy of at least 12 weeks (as assessed by the treating physician).
- Patient must have a white cell blood (WBC) count of \< 25 x 109/L. Hydroxyurea can be used prior to study enrollment to reduce the WBC count to meet this criterion.
- Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of normal (ULN) or creatinine clearance \>30 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR).
- Adequate hepatic function as evidenced by:
- Serum total bilirubin ≤ 3.0 × ULN unless considered due to Gilbert's disease, or leukemic involvement. If a patient meets this criterion, sponsor must be informed via HO173@erasmusmc.nl Page 30 of 117 HOVON 173 AML / AMLSG 34-23 / ACT-HOV-AML-001 Version 1.1, UK 11 FEB 2025
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement. If a patient meets this criterion, sponsor must be informed via HO173@erasmusmc.nl
- +10 more criteria
You may not qualify if:
- Subject has previously been treated for AML; a treatment period with hydroxyurea to control WBC counts is allowed; prior treatment with a hypomethylating agent for MDS-EB is not allowed; prior treatment with erythropoiesis-stimulating agents or luspatercept for MDS is allowed.
- Acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.2); PML-RARA; or one of the other pathognomonic variant chromosomal translocations / fusion genes.
- AML with BCR-ABL1; or myeloid blast crisis of CML
- Significant active cardiac disease within 3 months prior to the start of study treatment, including:
- \- New York Heart Association (NYHA) class III or IV congestive heart failure (Appendix F)
- \- Myocardial infarction
- \- Unstable angina
- Severe cardiac arrhythmias
- Congenital long QT syndrome of family member with this condition
- QTcF \>480 msec on screening electrogram (mean of triplicate recordings).
- Familial history of sudden death or polymorphic ventricular arrhythmia.
- Severe obstructive or restrictive ventilation disorder.
- History of stroke or intracranial hemorrhage within 6 months prior to randomization.
- Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
- Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Stichting Hemato-Oncologie voor Volwassenen Nederlandlead
- German-Austrian Acute Myeloid Leukemia Study Groupcollaborator
- United Kingdom AML Research Networkcollaborator
- Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA)collaborator
- Swiss Group for Clinical Cancer Research (SAKK)collaborator
- Danish Acute Leukemia Groupcollaborator
- Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasiascollaborator
- Nordic AML Groupcollaborator
Study Sites (119)
AT-Feldkirch-IKHF
Feldkirch, Austria
AT-Salzburg-SALK
Salzburg, Austria
AT-Vienna-HANUSCH
Vienna, Austria
BE-Antwerpen-ZAS
Antwerp, Belgium
BE-Brussel-BORDET
Brussels, Belgium
BE-Brussel-UZBRUSSEL
Brussels, Belgium
BE-Bruxelles-STLUC
Brussels, Belgium
BE-Gent-UZGENT
Ghent, Belgium
BE-Leuven-UZLEUVEN
Leuven, Belgium
BE-Liege-CHULIEGE
Liège, Belgium
BE-Yvoir-MONTGODINNE
Yvoir, Belgium
DK-Aalborg-AALBORGUH
Aalborg, Denmark
DK-Aarhus N-AUH
Aarhus N, Denmark
DK-Copenhagen-RIGSHOSPITALET
Copenhagen, Denmark
DK-Odense-OUH
Odense, Denmark
DK-Roskilde-ROSKILDE
Roskilde, Denmark
EE-Tallinn-REGIONAALHAIGLA
Tallinn, Estonia
EE-Tartu-TARTU
Tartu, Estonia
FI-Helsinki-HUS
Helsinki, Finland
FI-Tampere-TAYS
Tampere, Finland
FR-Angers-CHUANGERS
Angers, France
FR-Pessac Cedex-CHUBORDEAUX
Bordeaux, France
FR-Caen-CHUCAEN
Caen, France
FR-Créteil cedex-CHUMONDOR
Créteil, France
FR-Grenoble cedex 9-CHUGRENOBLE
Grenoble, France
FR-Lille-CHULILLE
Lille, France
FR-Lyon Pierre Benite cedex-LYONSUD
Lyon, France
FR-Montpellier-CHUSAINTELOIS
Montpellier, France
FR-Nantes-CHUNANTES
Nantes, France
FR-Nice-LARCHET
Nice, France
FR-Rennes cedex 9-CHURENNES
Rennes, France
FR-Rouen cedex-BECQUEREL
Rouen, France
FR-Saint-Priest-en-Jarez-STETIENNE
Saint-Etienne, France
FR-Le Chesnay cedex-CHVERSAILLES
Versailles, France
DE-Berlin-CAMPUSBENFRANKLIN
Berlin, Germany
DE-Berlin-CAMPUSVIRCHOW
Berlin, Germany
DE-Berlin-VIVANTESNEUKOLLN
Berlin, Germany
DE-Bochum-RUB
Bochum, Germany
DE-Bonn-UNIBONN
Bonn, Germany
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
Braunschweig, Germany
DE-Bremen-KBM
Bremen, Germany
DE-Darmstadt-KLINIKUMDARMSTADT
Darmstadt, Germany
DE-Flensburg-MALTESER
Flensburg, Germany
DE-Freiburg-UNIKLINIKFREIBURG
Freiburg im Breisgau, Germany
DE-Greifswald-UNIGREIFSWALD
Greifswald, Germany
DE-Halle-UMH
Halle, Germany
DE-Hamburg-ASKLEPIOSSTGEORG
Hamburg, Germany
DE-Hamburg-UKE
Hamburg, Germany
DE-Hannover-MHHANNOVER
Hanover, Germany
DE-Hannover-SILOAHKRH
Hanover, Germany
DE-Heilbronn-SLK
Heilbronn, Germany
DE-Karlsruhe-KLINIKUMKARLSRUHE
Karlsruhe, Germany
DE-Mainz-UNIMEDIZINMAINZ
Mainz, Germany
DE-Minden-MUEHLENKREISKLINKEN
Minden, Germany
DE-München-IRZTUM
München, Germany
DE-Oldenburg-KLINIKUMOLDENBURG
Oldenburg, Germany
DE-Regensburg-UKR
Regensburg, Germany
DE-Stuttgart-KLINIKUMSTUTTGART
Stuttgart, Germany
DE-Tübingen-MEDUNITUEBINGEN
Tübingen, Germany
DE-Ulm-UNIKLINKULM
Ulm, Germany
IE-Cork-CUH
Cork, Ireland
IE-Dublin 7-MATER
Dublin, Ireland
IE-Dublin 8-ST JAMES
Dublin, Ireland
IE-Galway-UHGALWAY
Galway, Ireland
IT-Bologna-MALPHIGI
Bologna, Italy
IT-Milano-NIGUARDA
Milan, Italy
IT-Roma-SAPIENZA
Roma, Italy
IT-Roma-TORVERGATA
Roma, Italy
IT-Torino-CITTADELLASALUTE
Torino, Italy
LT-Vilnius-SANTA
Vilnius, Lithuania
NL-Den Bosch-JBZ
's-Hertogenbosch, Netherlands
NL-Amsterdam-VUMC
Amsterdam, Netherlands
NL-Arnhem-RIJNSTATE
Arnhem, Netherlands
NL-Breda-AMPHIA
Breda, Netherlands
NL-Dordrecht-ASZ
Dordrecht, Netherlands
NL-Eindhoven-CATHARINA
Eindhoven, Netherlands
NL-Enschede-MST
Enschede, Netherlands
NL-Sittard-Geleen-ZUYDERLAND
Geleen, Netherlands
NL-Groningen-UMCG
Groningen, Netherlands
NL-Nijmegen-RADBOUDUMC
Nijmegen, Netherlands
NL-Rotterdam-ERASMUSMC
Rotterdam, Netherlands
NL-DenHaag-HAGA
The Hague, Netherlands
NL-Utrecht-UMCU
Utrecht, Netherlands
NL-Zwolle-ISALA
Zwolle, Netherlands
NO-Bergen-HELSEBERGEN
Bergen, Norway
NO-Oslo-OSLOUH
Oslo, Norway
NO-Tromsø-NORTHNOORWEGEN
Tromsø, Norway
NO-Trondheim-STOLAV
Trondheim, Norway
ES-Barcelona-CLINICUB
Barcelona, Spain
ES-Barcelona-GERMANTRIALS
Barcelona, Spain
ES-Barcelona-SANTPAU
Barcelona, Spain
ES-Girona-ICSTRUETA
Girona, Spain
ES-Valencia-MALVARROSA
Valencia, Spain
SE-Goteborg-SAHLGRENSKA
Gothenburg, Sweden
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-Zurich-USZ
Zurich, Switzerland
UK-Birmingham-QE
Birmingham, United Kingdom
UK-Blackpool-BLACKPOOLVICTORIA
Blackpool, United Kingdom
UK-Bristol-BRISTOLCENTRE
Bristol, United Kingdom
UK-Cardiff-UHW
Cardiff, United Kingdom
UK-Glasgow-BEATSON
Glasgow, United Kingdom
UK-Leeds-STJAMESUH
Leeds, United Kingdom
UK-Leicester-LEICESTERRI
Leicester, United Kingdom
UK-London-KCH
London, United Kingdom
UK-London-ROYALMARSDEN
London, United Kingdom
UK-London-UNICOLLEGEHOSP
London, United Kingdom
UK-Manchester-CHRISTIE
Manchester, United Kingdom
UK-Manchester-ROYALINFIRMARY
Manchester, United Kingdom
UK-Newcastle on Tyne-FREEMAN
Newcastle upon Tyne, United Kingdom
UK-Nottingham-NOTTINGHAMCH
Nottingham, United Kingdom
UK-Oxford-CHURCHILL
Oxford, United Kingdom
UK-Portsmouth-QUEENALEXANDRA
Portsmouth, United Kingdom
UK-Southampton-SOUTHAMPTONGH
Southampton, United Kingdom
UK-Wolverhampton-NEWCROSSH
Wolverhampton, United Kingdom
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 19, 2025
First Posted
July 20, 2025
Study Start
August 5, 2025
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
March 1, 2029
Last Updated
August 19, 2025
Record last verified: 2025-08