Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2

Last updated: June 30, 2025
Sponsor: University of Ulm
Overall Status: Active - Recruiting

Phase

3

Condition

Acute Myeloid Leukemia

White Cell Disorders

Myelodysplastic Syndromes (Mds)

Treatment

Autologous stem cell transplantation

Venetoclax

Placebo

Clinical Study ID

NCT04628026
AMLSG31-19/HO501/AbbVieB18-982
  • Ages 18-75
  • All Genders

Study Summary

A Randomized, Placebo-Controlled Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patients with newly diagnosed acute myeloid leukemia (AML) according to the International Consensus Classification (ICC).

  2. Age ≥ 18 and ≤ 75 years.

  3. Patients considered eligible for intensive chemotherapy.

  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

  5. Molecular analysis centrally performed in AMLSG and HOVON laboratories.

  6. Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR).

  7. Adequate hepatic function as evidenced by:

  • Serum total bilirubin ≤ 2.5 × ULN unless considered due to Gilbert's disease, or leukemic involvement following approval by the Principal Investigators or Trial Coordinators of the study

  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement following approval by the Principal Investigators or Trial Coordinators.

  1. No prior chemotherapy for AML, except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts > 25x109/L); patients may have had previous treatment with erythroid stimulating agents (ESA) or hypomethylating agents (HMAs) for an antecedent phase of MDS; ESA and HMAs have to be stopped at least four weeks before start of study treatment.

  2. Patients must not have received a known strong or moderate CYP3A inducer 7 days before start of study treatment. Patients must have no known medical conditions requiring chronic therapy with moderate or strong CYP3A inducers.

  3. Female patient must either:

  • Be of nonchildbearing potential:

  • Postmenopausal (defined as at least 1 year without any menses)

  • Documented surgically sterile (e.g. documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy or congenital sterile) or status post hysterectomy (at least 1 month prior to screening)

  • Or, if of childbearing potential (not surgically sterile and not postmenopausal)

  • Not planning 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 apply one highly effective* method of birth control in combination to a barrier method for the duration of the study and for 27 weeks after the final study drug administration

*Highly effective forms of birth control include

  • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation for at least 1 month prior to taking study drug. (hormonal contraception is only a highly effective method of birth control, if a combined [estrogen and progestogen containing] hormonal contraception or a progestogen-only hormonal contraception - both associated with inhibition of ovulation - is used.

  • Established intrauterine device (IUD) or intrauterine system (IUS)

  • Bilateral tubal occlusion

  • Vasectomy - a vasectomy is 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 enrolment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control in combination with a barrier method according to locally accepted standards 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 27 weeks after the final study drug administration.

  1. Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 27 weeks after the final study drug administration). In addition, their female partners of childbearing potential have to use a highly effective method of birth control.

  2. Male patient must not donate sperm starting at screening and throughout the study period and for 27 weeks after the final study drug administration.

  3. Able to understand and willing to sign an informed consent form (ICF).

Study Design

Total Participants: 650
Treatment Group(s): 5
Primary Treatment: Autologous stem cell transplantation
Phase: 3
Study Start date:
September 13, 2022
Estimated Completion Date:
February 29, 2032

Study Description

Prospective, multicenter, double-blind, randomized, placebo-controlled phase 3 clinical study. The randomized phase of the study will be preceded by a feasibility run-in dose-escalation phase in patients with AML in which the venetoclax dose for the phase 3 part will be established.

After the feasibility run-in phase, eligible patients will be randomized to intensive chemotherapy with venetoclax or placebo. Patients will receive two cycles of induction chemotherapy; patients achieving CR or CRi after two cycles will continue with consolidation treatment according to initial randomization, and according to Cooperative Group-specific consolidation regimens or investigator choice. Patients achieving morphologic leukemia-free state (MLFS) only, may also continue consolidation treatment on protocol. Assignment to either allogeneic hematopoietic cell transplantation (HCT), conventional chemotherapy or autologous HCT will be done according to institutional standards, and based on (prognostic) disease characteristics, individual patient assessment, and established comorbidity risk scores (e.g., HCT-CI score).

Connect with a study center

  • Tirol Kliniken GmbH

    Innsbruck,
    Austria

    Site Not Available

  • Kepler Universitaetsklinikum GmbH

    Linz,
    Austria

    Site Not Available

  • Ordensklinikum Linz GmbH

    Linz,
    Austria

    Site Not Available

  • Landeskrankenhaus (LKH) Rankweil, Interne E am Landeskrankenhaus Rankweil

    Rankweil,
    Austria

    Site Not Available

  • Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

    Salzburg,
    Austria

    Site Not Available

  • Hanusch Krankenhaus Der Wiener Gebietskrankenkasse

    Vienna,
    Austria

    Site Not Available

  • Ziekenhuis Aan De Stroom

    Antwerpen,
    Belgium

    Site Not Available

  • Az St-Jan Brugge-Oostende A.V.

    Brugge,
    Belgium

    Site Not Available

  • Universitair Ziekenhuis Brussel

    Brussels,
    Belgium

    Site Not Available

  • Katholieke Universiteit te Leuven

    Leuven,
    Belgium

    Site Not Available

  • Algemeen Ziekenhuis Delta

    Roeselare,
    Belgium

    Site Not Available

  • CHU UCL NAMUR - Mont Godinne

    Yvoir,
    Belgium

    Site Not Available

  • North Estonia Medical Centre Foundation

    Tallinn,
    Estonia

    Site Not Available

  • Tartu University Hospital

    Tartu,
    Estonia

    Site Not Available

  • Helsinki University Central Hospital Meilahden Kolmiosairaala

    Helsinki,
    Finland

    Site Not Available

  • Tampere University Hospital

    Tampere,
    Finland

    Site Not Available

  • Klinikum Aschaffenburg-Alzenau gGmbH

    Aschaffenburg,
    Germany

    Site Not Available

  • HELIOS Klinikum Bad Saarow GmbH

    Bad Saarow,
    Germany

    Site Not Available

  • Charité Berlin - Campus Benjamin Franklin

    Berlin, 12200
    Germany

    Active - Recruiting

  • Charité Berlin - Campus Mitte

    Berlin, 10117
    Germany

    Active - Recruiting

  • Charité Berlin - Campus Virchow Klinikum

    Berlin,
    Germany

    Active - Recruiting

  • Vivantes Neukölln

    Berlin,
    Germany

    Site Not Available

  • Vivantes Spandau

    Berlin,
    Germany

    Site Not Available

  • Vivantes am Urban

    Berlin,
    Germany

    Site Not Available

  • Knappschaftskrankenhaus Bochum-Langendreer

    Bochum, 44892
    Germany

    Active - Recruiting

  • Uniklinikum Bonn

    Bonn, 53127
    Germany

    Active - Recruiting

  • Staedtisches Klinikum Braunschweig

    Braunschweig, 38114
    Germany

    Active - Recruiting

  • Gesundheit Nord gGmbH Klinikverbund Bremen

    Bremen,
    Germany

    Site Not Available

  • Klinikum Darmstadt GmbH

    Darmstadt,
    Germany

    Site Not Available

  • St. Johannes Hospital Dortmund

    Dortmund,
    Germany

    Site Not Available

  • Marien Hospital Duesseldorf GmbH

    Düsseldorf,
    Germany

    Site Not Available

  • Klinikum Frankfurt Hoechst GmbH

    Frankfurt,
    Germany

    Site Not Available

  • Justus-Liebig-Universitaet Giessen

    Gießen,
    Germany

    Site Not Available

  • Wilhelm-Anton-Hospital Goch

    Goch,
    Germany

    Site Not Available

  • Universitätsmedizin Greifswald

    Greifswald,
    Germany

    Site Not Available

  • Asklepios Klinik Altona

    Hamburg,
    Germany

    Site Not Available

  • Asklepios Klinik St Georg

    Hamburg,
    Germany

    Site Not Available

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246
    Germany

    Active - Recruiting

  • KRH Klinikum Siloah

    Hannover,
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover

    Hannover, 30625
    Germany

    Active - Recruiting

  • SLK-Kliniken Heilbronn GmbH

    Heilbronn,
    Germany

    Site Not Available

  • Marien Hospital Herne

    Herne,
    Germany

    Site Not Available

  • Universitaetsklinikum des Saarlandes AöR

    Homburg,
    Germany

    Site Not Available

  • Staedtisches Klinikum Karlsruhe gGmbH

    Karlsruhe,
    Germany

    Site Not Available

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133
    Germany

    Active - Recruiting

  • Klinikum der Stadt Ludwigshafen am Rhein gGmbH

    Ludwigshafen,
    Germany

    Site Not Available

  • UNIVERSITÄTSKLINIKUM Schleswig-Holstein

    Lübeck,
    Germany

    Site Not Available

  • Otto Von Guericke Universitaet Magdeburg

    Magdeburg,
    Germany

    Site Not Available

  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

    Mainz,
    Germany

    Site Not Available

  • Klinikum Hochsauerland GmbH

    Meschede,
    Germany

    Site Not Available

  • Muhlenkreiskliniken AöR

    Minden,
    Germany

    Site Not Available

  • Klinikum rechts der Isar der TU Muenchen AöR

    München,
    Germany

    Site Not Available

  • Klinikum Oldenburg AöR

    Oldenburg,
    Germany

    Site Not Available

  • Universitaetsklinikum Regensburg AöR

    Regensburg,
    Germany

    Site Not Available

  • Diakonie Klinikum Stuttgart

    Stuttgart, 70176
    Germany

    Active - Recruiting

  • Barmherzige Brueder Trier gGmbH

    Trier,
    Germany

    Site Not Available

  • Uniklinikum Tübingen

    Tübingen, 72076
    Germany

    Active - Recruiting

  • University Hospital Ulm

    Ulm, 89081
    Germany

    Active - Recruiting

  • Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

    Villingen-Schwenningen,
    Germany

    Site Not Available

  • Helios Universitaetsklinikum Wuppertal

    Wuppertal,
    Germany

    Site Not Available

  • Vilnius University Hospital Santaros Klinik

    Vilnius,
    Lithuania

    Site Not Available

  • Meander Medisch Centrum

    Amersfoort,
    Netherlands

    Site Not Available

  • Amsterdam UMC Stichting

    Amsterdam,
    Netherlands

    Site Not Available

  • OLVG

    Amsterdam,
    Netherlands

    Site Not Available

  • Rijnstate Ziekenhuis Stichting

    Arnhem,
    Netherlands

    Site Not Available

  • Amphia Hospital

    Breda,
    Netherlands

    Site Not Available

  • Reinier de Graaf Gasthuis

    Delft,
    Netherlands

    Site Not Available

  • Jeroen Bosch ziekenhuis

    Den Bosch,
    Netherlands

    Site Not Available

  • Hagaziekenhuis, locatie Leyweg

    Den Haag,
    Netherlands

    Site Not Available

  • Albert Schweitzer Ziekenhuis

    Dordrecht,
    Netherlands

    Site Not Available

  • Maxima Medisch Centrum

    Eindhoven,
    Netherlands

    Site Not Available

  • Medisch Spectrum Twente

    Enschede,
    Netherlands

    Site Not Available

  • UMCG

    Groningen,
    Netherlands

    Site Not Available

  • Medisch Centrum Leeuwarden B.V.

    Leeuwarden,
    Netherlands

    Site Not Available

  • Leids Universitair Medisch Centrum (LUMC)

    Leiden,
    Netherlands

    Site Not Available

  • Maastricht University Medical Center+ (MUMC+)

    Maastricht,
    Netherlands

    Site Not Available

  • Sint Antonius Ziekenhuis Stichting

    Nieuwegein,
    Netherlands

    Site Not Available

  • Radboudumc

    Nijmegen,
    Netherlands

    Site Not Available

  • Erasmus MC - Daniel

    Rotterdam,
    Netherlands

    Site Not Available

  • UMCU

    Utrecht,
    Netherlands

    Site Not Available

  • Isala Klinieken Stichting

    Zwolle,
    Netherlands

    Site Not Available

  • Haukeland University Hospital

    Bergen,
    Norway

    Site Not Available

  • Stavanger Univ. Hosp.-Rogaland Hosp.

    Oslo,
    Norway

    Site Not Available

  • University Hospital of North Norway

    Tromsø,
    Norway

    Site Not Available

  • St. Olavs Hospital

    Trondheim,
    Norway

    Site Not Available

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