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

NCT04628026 | Recruiting Phase 3 DMC

• 1 other identifier: AMLSG31-19/HO501/AbbVieB18-982
• Study Type: interventional
• Target: 650
• Locations: 8 countries
• Sites: 91

Brief 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

Conditions

Acute Myeloid Leukemia

Keywords

adult patients

Outcome Measures

Primary Outcomes (2)

• Event Free Survival (EFS)

  EFS in adult patients with newly diagnosed AML, defined as the time from randomization to treatment failure, death from any cause, or relapse after achieving CR or CRi, or start of new therapy due to confirmed molecular relapse whichever occurs first. Treatment failure is defined as not attaining CR or CRi after induction chemotherapy, and EFS event time for treatment failure is Day 1 of post-randomization

  6 months/16 months after inclusion of last patient

• Frequency of dose-limiting toxicities (DLTs) during the observation period (Primary safety endpoint during dose-finding phase)

  Frequency of dose-limiting toxicities (DLTs) during the observation period (from start of cycle 1 up to a maximum of day 42, or until the start of cycle 2)

  after cycle 1 (maximal day 42)

Secondary Outcomes (14)

• Overall Survival (OS)

  6 months/16 months/28 months after inclusion of last patient

• CR/CRi rate

  2 months

• CR rate

  2 months

• Event Free Survival (EFS) including CRh

  6 months/16 months after inclusion of last patient

• Rates of complete remission without measurable residual disease (CRMRD-) after induction therapy

  2 months

Other Outcomes (15)

• Rates of CR+CRi in newly diagnosed AML patients after induction 1

  1 month

• Rates of CR in newly diagnosed AML patients after induction 1

  1 month

• EFS in newly diagnosed AML patients across different patient subgroups

  6 months/16 months after inclusion of last patient

Study Arms (2)

1

EXPERIMENTAL

standard chemotherapy in combination with venetoclax

Drug: Venetoclax; Combination Product: Standard chemotherapy; Other: Allogeneic stem cell transplantation

2

PLACEBO COMPARATOR

standard chemotherapy in combination with placebo

Drug: Placebo; Combination Product: Standard chemotherapy; Other: Allogeneic stem cell transplantation

Interventions

Venetoclax DRUG

Venetoclax will be administered in Induction cycle 1, Induction cycle 2 and in the chemo consolidation therapy in addition to the standard chemotherapy

1

Placebo DRUG

Placebo will be administered in Induction cycle 1, Induction cycle 2 and in the chemo consolidation therapy in addition to the standard chemotherapy

2

Standard chemotherapy COMBINATION_PRODUCT

Induction cycle 1: Patients will receive cytarabine 200 mg/m2 continuous IV (days 1-7) and daunorubicin 60 mg/m2 IV (days 1-3). Induction cycle 2: Patients ≤ 60 yrs will receive cytarabine 1000 mg/m2 BID (3h IV), days 1-4, and daunorubicin 60 mg/m2 IV (days 1-3). Patients \>60 yrs will receive cytarabine 1000 mg/m2 BID (3h IV), days 1-4 without daunorubicin. Consolidation chemotherapy with intermediate doses of cytarabine. Patients ≤60 yrs will receive up to 3 cycles of IDAC (single dose 1500 mg/m2 every 12 hours, days 1-3). Patients who are \>60 yrs will receive up to 3 cycles of IDAC with single doses of 1000 mg/m2, every 12 hours, days 1-3. In patients \>60 yrs less than 3 cycles of IDAC or dose-reduced IDAC (500 mg/m2 per single dose) may be given based on an individual risk assessment.

1; 2

Allogeneic stem cell transplantation OTHER

Generally, patients will proceed to allogeneic HCT upon completion of remission induction chemotherapy. It is however allowed, as per investigator's discretion, for a patient to receive 'bridging' consolidation chemotherapy in exceptional cases of delay towards transplantation. At baseline, HLA-compatible donor search must be initiated as soon as possible, first among siblings and second in the world donor bank for unrelated donors or cord blood. In order to avoid inappropriate delay in cases where no suitable sibling is present, high-resolution HLA typing should be performed immediately after registration, enabling a more rapid matched-unrelated donor search. In case no sibling or unrelated donor can be identified, haploidentical allogeneic HCT is allowed. Conditioning and GVHD prophylaxis will take place according to institutional guidelines. Patients who undergo allogeneic HCT will not receive venetoclax during conditioning, engraftment or after hematologic recovery.

1; 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed acute myeloid leukemia (AML) according to the International Consensus Classification (ICC).
• Age ≥ 18 and ≤ 75 years.
• Patients considered eligible for intensive chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Molecular analysis centrally performed in AMLSG and HOVON laboratories.
• 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).
• 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.
• 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.
• 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.
• 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)

Sponsors & Collaborators

• University of Ulm: lead
• Stichting Hemato-Oncologie voor Volwassenen Nederland: collaborator

Study Sites (91)

Tirol Kliniken GmbH

Innsbruck, Austria

NOT YET RECRUITING

Kepler Universitaetsklinikum GmbH

Linz, Austria

NOT YET RECRUITING

Ordensklinikum Linz GmbH

Linz, Austria

NOT YET RECRUITING

Landeskrankenhaus (LKH) Rankweil, Interne E am Landeskrankenhaus Rankweil

Rankweil, Austria

NOT YET RECRUITING

Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Salzburg, Austria

NOT YET RECRUITING

Hanusch Krankenhaus Der Wiener Gebietskrankenkasse

Vienna, Austria

NOT YET RECRUITING

Ziekenhuis Aan De Stroom

Antwerp, Belgium

NOT YET RECRUITING

Az St-Jan Brugge-Oostende A.V.

Bruges, Belgium

NOT YET RECRUITING

Universitair Ziekenhuis Brussel

Brussels, Belgium

RECRUITING

Katholieke Universiteit te Leuven

Leuven, Belgium

NOT YET RECRUITING

Algemeen Ziekenhuis Delta

Roeselare, Belgium

RECRUITING

CHU UCL NAMUR - Mont Godinne

Yvoir, Belgium

RECRUITING

North Estonia Medical Centre Foundation

Tallinn, Estonia

NOT YET RECRUITING

Tartu University Hospital

Tartu, Estonia

RECRUITING

Helsinki University Central Hospital Meilahden Kolmiosairaala

Helsinki, Finland

NOT YET RECRUITING

Tampere University Hospital

Tampere, Finland

NOT YET RECRUITING

Klinikum Aschaffenburg-Alzenau gGmbH

Aschaffenburg, Germany

RECRUITING

HELIOS Klinikum Bad Saarow GmbH

Bad Saarow, Germany

RECRUITING

Charité Berlin - Campus Mitte

Berlin, 10117, Germany

RECRUITING

Charité Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

RECRUITING

Charité Berlin - Campus Virchow Klinikum

Berlin, Germany

RECRUITING

Vivantes am Urban

Berlin, Germany

NOT YET RECRUITING

Vivantes Neukölln

Berlin, Germany

NOT YET RECRUITING

Vivantes Spandau

Berlin, Germany

WITHDRAWN

Knappschaftskrankenhaus Bochum-Langendreer

Bochum, 44892, Germany

RECRUITING

Uniklinikum Bonn

Bonn, 53127, Germany

RECRUITING

Staedtisches Klinikum Braunschweig

Braunschweig, 38114, Germany

RECRUITING

Gesundheit Nord gGmbH Klinikverbund Bremen

Bremen, Germany

RECRUITING

Klinikum Darmstadt GmbH

Darmstadt, Germany

NOT YET RECRUITING

St. Johannes Hospital Dortmund

Dortmund, Germany

RECRUITING

Marien Hospital Duesseldorf GmbH

Düsseldorf, Germany

WITHDRAWN

Klinikum Frankfurt Hoechst GmbH

Frankfurt, Germany

RECRUITING

Justus-Liebig-Universitaet Giessen

Giessen, Germany

RECRUITING

Wilhelm-Anton-Hospital Goch

Goch, Germany

RECRUITING

Universitätsmedizin Greifswald

Greifswald, Germany

RECRUITING

Univeritätsklinikum

Halle, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Asklepios Klinik Altona

Hamburg, Germany

RECRUITING

Asklepios Klinik St Georg

Hamburg, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

KRH Klinikum Siloah

Hanover, Germany

NOT YET RECRUITING

SLK-Kliniken Heilbronn GmbH

Heilbronn, Germany

RECRUITING

Marien Hospital Herne

Herne, Germany

RECRUITING

Universitaetsklinikum des Saarlandes AöR

Homburg, Germany

RECRUITING

Wespfalz-Klinikum

Kaiserslautern, Germany

NOT YET RECRUITING

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

RECRUITING

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, Germany

NOT YET RECRUITING

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, Germany

RECRUITING

UNIVERSITÄTSKLINIKUM Schleswig-Holstein

Lübeck, Germany

RECRUITING

Otto Von Guericke Universitaet Magdeburg

Magdeburg, Germany

RECRUITING

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Mainz, Germany

RECRUITING

Klinikum Hochsauerland GmbH

Meschede, Germany

RECRUITING

Muhlenkreiskliniken AöR

Minden, Germany

RECRUITING

Klinikum rechts der Isar der TU Muenchen AöR

München, Germany

NOT YET RECRUITING

Ortenauklinikum

Offenburg, Germany

NOT YET RECRUITING

Klinikum Oldenburg AöR

Oldenburg, Germany

RECRUITING

Universitaetsklinikum Regensburg AöR

Regensburg, Germany

NOT YET RECRUITING

Universitaetsklinikum

Rostock, Germany

RECRUITING

Diakonie Klinikum Stuttgart

Stuttgart, 70176, Germany

RECRUITING

Klinikum Traunstein

Traunstein, Germany

RECRUITING

Barmherzige Brueder Trier gGmbH

Trier, Germany

NOT YET RECRUITING

Klinikum Mutterhaus der Borromaerinnen

Trier, Germany

RECRUITING

Uniklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

University Hospital Ulm

Ulm, 89081, Germany

RECRUITING

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH

Villingen-Schwenningen, Germany

RECRUITING

Helios Universitaetsklinikum Wuppertal

Wuppertal, Germany

RECRUITING

Vilnius University Hospital Santaros Klinik

Vilnius, Lithuania

NOT YET RECRUITING

Jeroen Bosch ziekenhuis

's-Hertogenbosch, Netherlands

RECRUITING

Meander Medisch Centrum

Amersfoort, Netherlands

RECRUITING

Amsterdam UMC Stichting

Amsterdam, Netherlands

RECRUITING

OLVG

Amsterdam, Netherlands

RECRUITING

Rijnstate Ziekenhuis Stichting

Arnhem, Netherlands

RECRUITING

Amphia Hospital

Breda, Netherlands

RECRUITING

Reinier de Graaf Gasthuis

Delft, Netherlands

RECRUITING

Albert Schweitzer Ziekenhuis

Dordrecht, Netherlands

RECRUITING

Maxima Medisch Centrum

Eindhoven, Netherlands

RECRUITING

Medisch Spectrum Twente

Enschede, Netherlands

RECRUITING

UMCG

Groningen, Netherlands

RECRUITING

Medisch Centrum Leeuwarden B.V.

Leeuwarden, Netherlands

RECRUITING

Leids Universitair Medisch Centrum (LUMC)

Leiden, Netherlands

RECRUITING

Maastricht University Medical Center+ (MUMC+)

Maastricht, Netherlands

NOT YET RECRUITING

Sint Antonius Ziekenhuis Stichting

Nieuwegein, Netherlands

RECRUITING

Radboudumc

Nijmegen, Netherlands

RECRUITING

Erasmus MC - Daniel

Rotterdam, Netherlands

RECRUITING

Hagaziekenhuis, locatie Leyweg

The Hague, Netherlands

RECRUITING

UMCU

Utrecht, Netherlands

NOT YET RECRUITING

Isala Klinieken Stichting

Zwolle, Netherlands

NOT YET RECRUITING

Haukeland University Hospital

Bergen, Norway

NOT YET RECRUITING

Stavanger Univ. Hosp.-Rogaland Hosp.

Oslo, Norway

NOT YET RECRUITING

University Hospital of North Norway

Tromsø, Norway

NOT YET RECRUITING

St. Olavs Hospital

Trondheim, Norway

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Hartmut Doehner, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hartmut Doehner, MD

CONTACT

004973150045501; harmut.doehner@uniklinik-ulm.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind with open label dose-finding run-in part
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 13, 2020
• Study Start: September 13, 2022
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): February 1, 2032
• Last Updated: April 21, 2026

Record last verified: 2026-03

Locations

FI (2); LI (1); DE (50); NO (4); AU (6); BE (6); NL (20); ES (2)