Acute Myeloid LeukemiaPhase 3EVOLVE 1NCT07075016

Ivosidenib and Azacitidine With or Without Venetoclax in Adult Patients With Newly Diagnosed IDH1-Mutated AML or MDS/AML Considered Ineligible for Intensive Chemotherapy

A Phase 3 study testing Venetoclax 400 in people with Acute Myeloid Leukemia, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 119 sites in 16 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: Venetoclax 400
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 227 participants
Where: 119 sitesin 16 countries
Study dates: 5 Aug 2025to Mar 2029
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient with newly diagnosed IDH1-mutated AML, or IDH1-mutated MDS/AML according to the 2022 International Consensus Classification (Appendix A). Patients with AML with both IDH1 and IDH2 mutation are eligible as well. Of note: in case both NPM1 and IDH1 are mutated and both EVOLVE-1 (HO173/AMLSG 3423/ACT-HOV-AML-001) and EVOLVE-2 (HO177/AMLSG 35-24/ACT-HOV-AML-002are open for inclusion at your site, then patients can only be included in the EVOLVE-1 trial (HO173)
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).
18-74 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.

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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
Female patients :
of nonchildbearing potential must be: o postmenopausal (defined as at least 1 year without any menses). o documented surgically sterile (e.g. documented hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or status posthysterectomy (at least 1 month prior to screening).
of childbearing potential (not surgically sterile and not postmenopausal) must agree to avoid pregnancy during the study and for 6 months after the final study drug administration o and have a negative urine or serum pregnancy test at screening.
o and, if heterosexually active, agree to consistently apply one highly effective method of birth control in combination to a barrier method for the duration of the study and for 6 months after the final study drug administration.
must agree not to breastfeed starting at screening and throughout the study period, and for 1 month after the final study drug administration.
must agree not to donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Men must use a latex condom during any sexual contact with women of childbearing potential (WOCBP), even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 6 months after the final study drug administration). In addition, their female partners of childbearing potential must use a highly effective method of birth control.
Male patient must not donate sperm starting at screening and throughout the study period and for 6 months after the final study drug administration.
Able to understand and willing to sign an informed consent form (ICF).
Institutional Review Board/Independent Ethics Committee-approved written informed consent and privacy language as per national regulations must be obtained from the participant prior to any study-related procedures (including consent for withdrawal of prohibited medication, if applicable).

Who cannot join

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

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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.
Active infection, including hepatitis B or hepatitis C or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial; an infection controlled with an approved antibiotic/ antiviral/ antifungal treatment that is not a strong or moderate CYP3A inducer is allowed. Patients with COVID-19 infection can be enrolled, if the patient has no symptoms and was tested negative twice by PCR test prior to inclusion in the trial.
Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation.
Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs
Patient 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.
Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patient, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy).
Severe neurological or psychiatric disorder interfering with ability to give an informed consent.
Contraindication to any of the anti-leukemic agents used (as per SmPC). 16. Participation in other prospective studies with anti-leukemic and/or investigational agents.
17. Patient taking Dabigatran unless they can be transferred to other medications within ≥5 half-lives prior to dosing. Patients taking other P-gP transporter-sensitive medications (see Appendix J) should be properly monitored during the study if they cannot be transferred to other medications." 18. Patients taking known strong cytochrome P450 (CYP) 3A4 inducers (see Appendix H), unless they can be transferred to other medications within ≥5 half-lives prior to dosing.
19. The patient is a pregnant or lactating woman, or plans to become pregnant during the study.
20. Patient who has once been screened and randomized into this HO173 trial but was considered ineligible cannot re-enter this trial at a later date.
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Trial locations and contacts

119 sites in 16 countries. Contact the study team or a site near you to ask about taking part.

Country

City, postcode or hospital

Sites recruiting now only

119 sites in 16 countries

Germany26 sites, 26 recruiting

DE-Berlin-CAMPUSBENFRANKLIN
Berlin
Dr Jörg Westermann
Not yet recruiting
DE-Berlin-CAMPUSVIRCHOW
Berlin
Dr Jörg Westermann
Not yet recruiting
DE-Berlin-VIVANTESNEUKOLLN
Berlin
Prof. Dr. Maike de Wit
Not yet recruiting
DE-Bochum-RUB
Bochum
Dr Prof. Roland Schroers
Not yet recruiting
DE-Bonn-UNIBONN
Bonn
Dr Lino Teichman
Not yet recruiting
DE-Braunschweig-KLINIKUMBRAUNSCHWEIG
Braunschweig
Dr Carsten Springer
Not yet recruiting
DE-Bremen-KBM
Bremen
Prof. Dr. med. B. Hertenstein
Not yet recruiting
DE-Darmstadt-KLINIKUMDARMSTADT
Darmstadt
Dr Helga Bernhard
Not yet recruiting
DE-Flensburg-MALTESER
Flensburg
Dr N. Faber
Not yet recruiting
DE-Freiburg-UNIKLINIKFREIBURG
Freiburg im Breisgau
Prof. Dr. med Michael Lübbert
Not yet recruiting
DE-Greifswald-UNIGREIFSWALD
Greifswald
Prof. Dr. Adrian Schwarzer
Not yet recruiting
DE-Halle-UMH
Halle
Dr Michael Heuser
Not yet recruiting
DE-Hamburg-ASKLEPIOSSTGEORG
Hamburg
Prof. Dr. med. Ahmet Elmaagaclı
Not yet recruiting
DE-Hamburg-UKE
Hamburg
Dr Franziska Modemann
Not yet recruiting
DE-Hannover-MHHANNOVER
Hanover
Dr Felicitas Thol
Not yet recruiting
DE-Hannover-SILOAHKRH
Hanover
Dr. Daniela Dörfel
Not yet recruiting
DE-Heilbronn-SLK
Heilbronn
Dr Markus Lindauer
Not yet recruiting
DE-Karlsruhe-KLINIKUMKARLSRUHE
Karlsruhe
Prof. Dr. Mark Ringhoffer
Not yet recruiting
DE-Mainz-UNIMEDIZINMAINZ
Mainz
Dr Michael Kuehn
Not yet recruiting
DE-Minden-MUEHLENKREISKLINKEN
Minden
Dr Kai Wille
Not yet recruiting
DE-München-IRZTUM
München
Prof. Dr. Katharina Götze
Not yet recruiting
DE-Oldenburg-KLINIKUMOLDENBURG
Oldenburg
Dr Voß, Andreas
Not yet recruiting
DE-Regensburg-UKR
Regensburg
Dr D. Heudobler
Not yet recruiting
DE-Stuttgart-KLINIKUMSTUTTGART
Stuttgart
Dr Jesko Ingold
Not yet recruiting
DE-Tübingen-MEDUNITUEBINGEN
Tübingen
Prof. Dr. Claudia Lengerke
Not yet recruiting
DE-Ulm-UNIKLINKULM
Ulm
Prof. H. Döhner
Not yet recruiting

Other trials in Germany

United Kingdom18 sites, 18 recruiting

UK-Birmingham-QE
Birmingham
Dr Vidhya Murthy
Not yet recruiting
UK-Blackpool-BLACKPOOLVICTORIA
Blackpool
Dr Paul Cahalin
Not yet recruiting
UK-Bristol-BRISTOLCENTRE
Bristol
Dr Priyanka Mehta
Not yet recruiting
UK-Cardiff-UHW
Cardiff
Dr Steve Knapper
Not yet recruiting
UK-Glasgow-BEATSON
Glasgow
Dr Mhairi Copland
Not yet recruiting
UK-Leeds-STJAMESUH
Leeds
Dr Anjum Khan
Not yet recruiting
UK-Leicester-LEICESTERRI
Leicester
Dr Anna Tsoulkani
Not yet recruiting
UK-London-KCH
London
Dr Pramila Krishnamurthy
Not yet recruiting
UK-London-ROYALMARSDEN
London
Dr David Taussig
Not yet recruiting
UK-London-UNICOLLEGEHOSP
London
Dr Rob Sellar
Not yet recruiting
UK-Manchester-CHRISTIE
Manchester
Dr Mike Dennis
Not yet recruiting
UK-Manchester-ROYALINFIRMARY
Manchester
Dr Eleni Tholouli
Not yet recruiting
UK-Newcastle on Tyne-FREEMAN
Newcastle upon Tyne
Dr Jones Gail
Not yet recruiting
UK-Nottingham-NOTTINGHAMCH
Nottingham
Dr Gerardo Errico
Not yet recruiting
UK-Oxford-CHURCHILL
Oxford
Dr Paresh Vyas
Not yet recruiting
UK-Portsmouth-QUEENALEXANDRA
Portsmouth
Dr Edward Belsham
Not yet recruiting
UK-Southampton-SOUTHAMPTONGH
Southampton
Dr Srinivasan Narayanan
Not yet recruiting
UK-Wolverhampton-NEWCROSSH
Wolverhampton
Dr Richard Whitmill
Not yet recruiting

Other trials in United Kingdom

France14 sites, 14 recruiting

FR-Angers-CHUANGERS
Angers
Dr Mathilde Hunault-Berger
Not yet recruiting
FR-Pessac Cedex-CHUBORDEAUX
Bordeaux
Dr Pierre-Yves Dumas
Not yet recruiting
FR-Caen-CHUCAEN
Caen
Dr Sylvain Chantepie
Not yet recruiting
FR-Créteil cedex-CHUMONDOR
Créteil
Dr Mathieu Leclerc
Not yet recruiting
FR-Grenoble cedex 9-CHUGRENOBLE
Grenoble
Dr Martin Carre
Not yet recruiting
FR-Lille-CHULILLE
Lille
Dr Céline Berthon
Not yet recruiting
FR-Lyon Pierre Benite cedex-LYONSUD
Lyon
Dr Mael Heiblig
Not yet recruiting
FR-Montpellier-CHUSAINTELOIS
Montpellier
Dr Ludovic Gabellier
Not yet recruiting
FR-Nantes-CHUNANTES
Nantes
Dr Pierre Peterlin
Not yet recruiting
FR-Nice-LARCHET
Nice
Dr Thomas Cluzeau
Not yet recruiting
FR-Rennes cedex 9-CHURENNES
Rennes
Dr Tony Marchand
Not yet recruiting
FR-Rouen cedex-BECQUEREL
Rouen
Dr Emilie Lemasle
Not yet recruiting
FR-Saint-Priest-en-Jarez-STETIENNE
Saint-Etienne
Dr Emmanuelle Tavernier
Not yet recruiting
FR-Le Chesnay cedex-CHVERSAILLES
Versailles
Dr Juliette Lambert
Not yet recruiting

Other trials in France

Netherlands14 sites, 14 recruiting

NL-Den Bosch-JBZ
's-Hertogenbosch
Dr. Alexandra Herbers
Not yet recruiting
NL-Amsterdam-VUMC
Amsterdam
Dr de Leeuw
Not yet recruiting
NL-Arnhem-RIJNSTATE
Arnhem
Dr Marloes Cuijpers
Not yet recruiting
NL-Breda-AMPHIA
Breda
Dr Roel Fiets
Not yet recruiting
NL-Dordrecht-ASZ
Dordrecht
Dr Westerweel
Not yet recruiting
NL-Eindhoven-CATHARINA
Eindhoven
Dr Marjan Cruijsen
Not yet recruiting
NL-Enschede-MST
Enschede
Dr. Tjeerd Snijders
Not yet recruiting
NL-Sittard-Geleen-ZUYDERLAND
Geleen
Dr R.J.W. van Kampen
Not yet recruiting
NL-Groningen-UMCG
Groningen
Dr G.A. Huls, +31 50 361 1761, g.huls@umcg.nl
Recruiting
NL-Nijmegen-RADBOUDUMC
Nijmegen
Dr JJWM Janssen
Not yet recruiting
NL-Rotterdam-ERASMUSMC
Rotterdam
Dr B.Wouters
Not yet recruiting
NL-DenHaag-HAGA
The Hague
Dr D. van Lammeren
Not yet recruiting
NL-Utrecht-UMCU
Utrecht
Dr A van Rhenen
Not yet recruiting
NL-Zwolle-ISALA
Zwolle
Dr Tim de Waal
Not yet recruiting

Other trials in Netherlands

Belgium8 sites, 8 recruiting

BE-Antwerpen-ZAS
Antwerp
Dr Heyrman
Not yet recruiting
BE-Brussel-BORDET
Brussels
Dr. Sebastian Wittnebel
Not yet recruiting
BE-Brussel-UZBRUSSEL
Brussels
Dr Ann de Becker
Not yet recruiting
BE-Bruxelles-STLUC
Brussels
Dr Havelange
Not yet recruiting
BE-Gent-UZGENT
Ghent
Dr Delie
Not yet recruiting
BE-Leuven-UZLEUVEN
Leuven
Dr Maertens
Not yet recruiting
BE-Liege-CHULIEGE
Liège
Dr DeVoeght
Not yet recruiting
BE-Yvoir-MONTGODINNE
Yvoir
Dr Collinge, +3281423831, elodie.collinge@chuuclnamur.uclouvain.be
Recruiting

Other trials in Belgium

Denmark5 sites, 5 recruiting

DK-Aalborg-AALBORGUH
Aalborg
Dr Marianne Tang Severinsen
Not yet recruiting
DK-Aarhus N-AUH
Aarhus N
Dr Hans Beier Ommen
Not yet recruiting
DK-Copenhagen-RIGSHOSPITALET
Copenhagen
Dr Claudia Schöllkopf
Not yet recruiting
DK-Odense-OUH
Odense
Dr Claus Marcher
Not yet recruiting
DK-Roskilde-ROSKILDE
Roskilde
Dr. Jack Maibom
Not yet recruiting

Other trials in Denmark

Italy5 sites, 5 recruiting

IT-Bologna-MALPHIGI
Bologna
Dr Antonio Curti
Not yet recruiting
IT-Milano-NIGUARDA
Milan
Dr Roberto Cairoli
Not yet recruiting
IT-Roma-SAPIENZA
Roma
Dr Massimo Breccia
Not yet recruiting
IT-Roma-TORVERGATA
Roma
Dr Adriano Venditti
Not yet recruiting
IT-Torino-CITTADELLASALUTE
Torino
Dr Ernesta Audisio
Not yet recruiting

Other trials in Italy

Spain5 sites, 5 recruiting

ES-Barcelona-CLINICUB
Barcelona
Dr Jordi Esteve
Not yet recruiting
ES-Barcelona-GERMANTRIALS
Barcelona
Dr Susana Vives POLO
Not yet recruiting
ES-Barcelona-SANTPAU
Barcelona
Dr Ana Garrido
Not yet recruiting
ES-Girona-ICSTRUETA
Girona
Dr Rosa Coll Jorda
Not yet recruiting
ES-Valencia-MALVARROSA
Valencia
Dr Mar Tormo
Not yet recruiting

Other trials in Spain

Ireland4 sites, 4 recruiting

IE-Cork-CUH
Cork
Dr Vitaliy Mykytiv
Not yet recruiting
IE-Dublin 7-MATER
Dublin
Dr Michael Fay
Not yet recruiting
IE-Dublin 8-ST JAMES
Dublin
Dr Nina Orfali
Not yet recruiting
IE-Galway-UHGALWAY
Galway
Dr. Mark Gurney
Not yet recruiting

Other trials in Ireland

Norway4 sites, 4 recruiting

NO-Bergen-HELSEBERGEN
Bergen
Dr Bjørn Tore Gjertsen
Not yet recruiting
NO-Oslo-OSLOUH
Oslo
Dr Andrea Lenartova
Not yet recruiting
NO-Tromsø-NORTHNOORWEGEN
Tromsø
Dr Nils Morten Leknes
Not yet recruiting
NO-Trondheim-STOLAV
Trondheim
Dr Anne Sophie von Krogh
Not yet recruiting

Other trials in Norway

Sweden4 sites, 4 recruiting

SE-Goteborg-SAHLGRENSKA
Gothenburg
Dr Lovisa Vennström
Not yet recruiting
SE-Lund-SUH
Lund
Dr Vladimir Lazarevic
Not yet recruiting
SE-Stockholm-KAROLINSKAHUDDINGE
Stockholm
Dr Martin Jädersten
Not yet recruiting
SE-Uppsala-UPPSALAUH
Uppsala
Dr Anna Robelius
Not yet recruiting

Other trials in Sweden

Switzerland4 sites, 4 recruiting

CH-Basel-USB
Basel
Dr Corinne Widmer
Not yet recruiting
CH-Bellinzona-IOSI
Bellinzona
Dr Georg Stüssi
Not yet recruiting
CH-Bern-INSEL
Bern
Dr Thomas Pabst
Not yet recruiting
CH-Zurich-USZ
Zurich
Dr Alexandre Theocharides
Not yet recruiting

Other trials in Switzerland

Austria3 sites, 3 recruiting

AT-Feldkirch-IKHF
Feldkirch
Dr Bernd Hartmann
Not yet recruiting
AT-Salzburg-SALK
Salzburg
Dr Richard Greil
Not yet recruiting
AT-Vienna-HANUSCH
Vienna
Dr Dr.Elisabeth Koller
Not yet recruiting

Other trials in Austria

Estonia2 sites, 2 recruiting

EE-Tallinn-REGIONAALHAIGLA
Tallinn
Dr Katrin Palk
Not yet recruiting
EE-Tartu-TARTU
Tartu
Dr Ain Kaare
Not yet recruiting

Other trials in Estonia

Finland2 sites, 2 recruiting

FI-Helsinki-HUS
Helsinki
Dr Mika Kontro
Not yet recruiting
FI-Tampere-TAYS
Tampere
Dr Johanna Rimpilainen
Not yet recruiting

Other trials in Finland

Lithuania1 site, 1 recruiting

LT-Vilnius-SANTA
Vilnius
Dr Andrius Žučenka
Not yet recruiting

Other trials in Lithuania

About this study

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'.

Conditions: Acute Myeloid Leukemia
Being tested: Venetoclax 400, Placebo
Keywords: IDH1, Newly AML diagnosed, Ineligible for intensive chemotherapy
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Venetoclax 400Drug
day 1-28 per cycle
PlaceboDrug
day 1-28 per cycle

Study groups in NCT07075016
Study group	Role	What they receive
Placebo comparator: Venetoclax-placebo	Placebo comparator	day 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) Receives: Drug: Placebo
Experimental: Venetoclax	Experimental	day 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) Receives: Drug: Venetoclax 400

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 12 months after inclusion of last AML patient

Secondary outcomes (8)

Overall survival (OS) in patients with newly diagnosed IDH1-mutated AML
Overall survival (OS) in patients with newly diagnosed IDH1-mutated AML, measured from the day of randomization to the date of death from any cause; patients not known to have died are censored on the date they were last known to be alive.
Measured: 12 months after inclusion of last AML patient
Rate of CR/CRh in patients with newly diagnosed IDH1-mutated AML
Rate of CR/CRh in patients with newly diagnosed IDH1-mutated AML, defined as the proportion of patients with CR/CRh at any time point during protocol therapy.
Measured: 12 months after inclusion of last AML patient
Rate of CR in patients with newly diagnosed IDH1-mutated AML
Rate of CR in patients with newly diagnosed IDH1-mutated AML, defined as the proportion of patients with CR at any time point during protocol therapy.
Measured: 12 months after inclusion of last AML patient
Rate of CR/CRi in patients with newly diagnosed IDH1-mutated AML
Rate of CR/CRi in patients with newly diagnosed IDH1-mutated AML, defined as the proportion of patients with CR/CRi at any time point during protocol therapy.
Measured: 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
Rates of CR, CR/CRh and CR/CRi without measurable residual disease as assessed by multicolor flow cytometry (CRMRD-, CR/CRhMRD- and CR/CRiMRD-) in patients with newly diagnosed IDH1-mutated AML, defined as the proportion patients with CRMRD-, CR/CRhMRD- and CR/CRiMRD-, respectively, at any time point during protocol therapy.
Measured: 12 months after inclusion of last AML patient
Time to achievement of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1-mutated AML
Time to achievement of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1-mutated AML, defined as time from the date of randomization until the 1st occurrence of response.
Measured: 12 months after inclusion of last AML patient
Duration of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1mutated AML
Duration of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1mutated AML, measured from the date of achievement of a response until the date of hematologic relapse or death from any cause; patients without any of these events will be censored on the date of last clinical assessment.
Measured: 12 months after inclusion of last AML patient
The rate of transfusion independence (platelets and RBC) in patients with newly diagnosed IDH1-mutated AML
The rate of transfusion independence (platelets and RBC) in patients with newly diagnosed IDH1-mutated AML, defined as the proportion of patients who achieved transfusion independence; transfusion independence is defined as a period of at least 56 days with no transfusion between the first dose of study drug and the last dose of study drug + 30 days.
Measured: A period of at least 56 days with no transfusion between the first dose of study drug and the last dose of study drug + 30 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Aug 2025Mar 2029

First posted20 Jul 2025
Study start5 Aug 2025
Primary completionDec 2028 (estimated)
Study completionMar 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 227 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07075016
Sponsor's protocol ID: HO173
Other IDs: 2024-512753-24
Acronym: EVOLVE 1
Status last verified: Aug 2025
First submitted: 19 Jun 2025
Last updated: 19 Aug 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
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All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Ivosidenib and Azacitidine With or Without Venetoclax in Adult Patients With Newly Diagnosed IDH1-Mutated AML or MDS/AML Considered Ineligible for Intensive Chemotherapy
ClinicalTrials.gov ID: NCT07075016
Acronym / sponsor ID: EVOLVE 1 / HO173
Conditions: Acute Myeloid Leukemia
Keywords: IDH1, Newly AML diagnosed, Ineligible for intensive chemotherapy
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 227 participants (estimated)
Lead sponsor: Stichting Hemato-Oncologie voor Volwassenen NederlandUniversity, hospital or other
Collaborators: German-Austrian Acute Myeloid Leukemia Study Group, United Kingdom AML Research Network, Gruppo Italiano Malattie EMatologiche dell'Adulto, Swiss Group for Clinical Cancer Research (SAKK), Danish Acute Leukemia Group, Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias, Nordic AML Group
Study start: 5 Aug 2025 (actual)
Primary completion: Dec 2028 (estimated)
Study completion: Mar 2029 (estimated)
First posted: 20 Jul 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo comparator: Venetoclax-placebo	Placebo comparator	Drug: Placeboday 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	Experimental	Drug: Venetoclax 400day 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)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (26 listed)

Patient with newly diagnosed IDH1-mutated AML, or IDH1-mutated MDS/AML according to the 2022 International Consensus Classification (Appendix A). Patients with AML with both IDH1 and IDH2 mutation are eligible as well. Of note: in case both NPM1 and IDH1 are mutated and both EVOLVE-1 (HO173/AMLSG 3423/ACT-HOV-AML-001) and EVOLVE-2 (HO177/AMLSG 35-24/ACT-HOV-AML-002are open for inclusion at your site, then patients can only be included in the EVOLVE-1 trial (HO173)
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:
Patient must have a projected life expectancy of at least 12 weeks (as assessed by the treating physician).

Key exclusion criteria (29 listed)

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:
Familial history of sudden death or polymorphic ventricular arrhythmia.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Venetoclax 400day 1-28 per cycle	Drug	Experimental: Venetoclax
Placeboday 1-28 per cycle	Drug	Placebo comparator: Venetoclax-placebo

Primary outcome

Event-free survival (EFS) in patients with newly diagnosed IDH1-mutated AML ineligible for intensive chemotherapy
Time frame: 12 months after inclusion of last AML patient
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.

8 secondary outcomes

Overall survival (OS) in patients with newly diagnosed IDH1-mutated AML
Time frame: 12 months after inclusion of last AML patient
Rate of CR/CRh in patients with newly diagnosed IDH1-mutated AML
Time frame: 12 months after inclusion of last AML patient
Rate of CR in patients with newly diagnosed IDH1-mutated AML
Time frame: 12 months after inclusion of last AML patient
Rate of CR/CRi in patients with newly diagnosed IDH1-mutated AML
Time frame: 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
Time frame: 12 months after inclusion of last AML patient
Time to achievement of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1-mutated AML
Time frame: 12 months after inclusion of last AML patient
Duration of response (CR, CR/CRh and CR/CRi) in patients with newly diagnosed IDH1mutated AML
Time frame: 12 months after inclusion of last AML patient
The rate of transfusion independence (platelets and RBC) in patients with newly diagnosed IDH1-mutated AML
Time frame: A period of at least 56 days with no transfusion between the first dose of study drug and the last dose of study drug + 30 days.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.
HOVON websiteLink provided by the sponsor.
Individual participant dataSharing planned: Undecided

Related trials for Acute Myeloid Leukemia

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

BE-Yvoir-MONTGODINNE

Yvoir, Belgium

+3281423831

elodie.collinge@chuuclnamur.uclouvain.be

NL-Groningen-UMCG

Groningen, Netherlands

+31 50 361 1761

g.huls@umcg.nl

119 sites in 16 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Venetoclax 400 in people with Acute Myeloid Leukemia, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 119 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 119 sites in Germany, United Kingdom, France, Netherlands, Belgium and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (EFS) in patients with newly diagnosed IDH1-mutated AML ineligible for intensive chemotherapy (time frame: 12 months after inclusion of last AML patient). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07075016.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2025.