System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Randomized Controlled Trial Multicenter Study Clinical Trial, Phase III Epublish

PubMed: 42563153 DOI: 10.1186/s12885-026-16617-8

DECIDER-2: Prospective randomized multicenter phase III trial of decitabine and venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy.

BMC Cancer 26(1)

Authors: Olga Grishina, Claudia Schmoor, Caroline Sellner, Björn Hackanson, Jan-Henrik Mikesch, Iordanis Deligiannis, Felicitas Thol, Martina Crysandt, Christian Junghanss, Volker Runde, Paul La Rosée, Lino Lars Teichmann, Haifa Kathrin Al-Ali, Tim Sauer, Ulrich Germing, Frank Griesinger, Stefan Lukic, Jürgen Krauter, Snjezana Janjetovic, Jan Koch, Peter Staib, Julian Topaly, Maike de Wit, Doris Maria Kraemer, Lorenz Oelschläger, Ulf Schnetzke, Oliver Schmah, Swen Wessendorf, Cyrus Khandanpour, Lukas Kündgen, Monika Schwalenberg, Michael Heuser, Arnold Ganser, Hartmut Döhner, Ralph Wäsch, Michael Lübbert

Affiliations

  • Clinical Trials Unit, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg, Elsaesser Str. 2, Freiburg, 79110, Germany.
  • Department of Hematology/Oncology, Comprehensive Cancer Center Augsburg as Part of the CCC-WERA Consortium, University Medical Center Augsburg, Stenglinstraße 2, Augsburg, 86156, Germany.
  • Department of Medicine A, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, 48149, Germany.
  • Internal Medicine I, Brothers Hospital Trier, Nordallee 1, Trier, 54292, Germany.
  • Department of Hematology, Hemostasis, Oncology, and Cell Therapy, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover, 30625, Germany.
  • Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Pauwelsstraße 30, Aachen, 52074, Germany.
  • Department of Internal Medicine, Clinic for Hematology, Stem Cell Therapy and Palliative Medicine, Rostock University Medical Center, Ernst-Heydemann-Straße 6, Hemostasis, Rostock, Oncology, 18055, Germany.
  • Department of Hematology, Oncology and Palliative Care, Wilhelm-Anton- Hospital, Voßheider Straße 214-232, Goch, 47574, Germany.
  • Department for Internal Medicine II, Schwarzwald-Baar Klinikum, Klinikstraße 11, Villingen-Schwenningen, 78052, Germany.
  • Department of Medicine III, University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
  • Krukenberg Cancer Center Halle, Medical Faculty, Martin-Luther- University Halle-Wittenberg, Ernst-Grube-Straße 40, Halle (Saale), 06120, Germany.
  • Department of Internal Medicine V, Heidelberg University Hospital, Im Neuenheimer Feld 410, Heidelberg, 69120, Germany.
  • Department of Hematology, Oncology, and Clinical Immunology, Heinrich- Heine University Düsseldorf, Moorenstraße 5, Düsseldorf, 40225, Germany.
  • Clinic for Hematology and Oncology, Pius-Hospital Oldenburg, University Medicine Oldenburg, Georgstraße 12, Oldenburg, 26121, Germany.
  • Department of Hematology and Oncology, Augusta-Kranken-Anstalt, Academic Teaching Hospital of the Ruhr-University Bochum, Bergstraße 26, Bochum, 44791, Germany.
  • Department of Hematology and Oncology, Municipal Hospital Braunschweig, Celler Straße 38, Braunschweig, 38114, Germany.
  • Department of Hematology and Cell Therapy, Helios Klinikum Berlin- Buch, Schwanebecker Chaussee 50, Berlin, 13125, Germany.
  • University Medical Center Mannheim (UMM), Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
  • Department of Hematology and Oncology, St Antonius Hospital Eschweiler, Dechant-Deckers-Straße 8, Eschweiler, 52249, Germany.
  • Department of Hematology and Oncology, CaritasKlinikum Saarbrücken, Rheinstraße 2, Saarbrücken, 66113, Germany.
  • Department of Internal Medicine, Hematology, Oncology and Palliative Medicine, Vivantes Klinikum Neukölln, Rudower Straße 48, Berlin, 12351, Germany.
  • St. Josefs-Hospital Hagen, Dreieckstraße 17, Hagen, 58097, Germany.
  • Department of Hematology and Oncology, Schleswig-Holstein, University Medical Center, University Cancer Center Schleswig-Holstein, Ratzeburger Allee 160, Lübeck, 23538, Germany.
  • Department of Hematology and Medical Oncology, Clinic for Internal Medicine II, Comprehensive Cancer Center Central Germany-Campus Jena, University Hospital Jena, Am Klinikum 1, Jena, 7747, Germany.
  • Section of Hematology and Oncology, Ortenau Medical Care Center, Ortenau Klinikum Lahr, Klostenstraße 19, Lahr, 77933, Germany.
  • Department of Hematology and Oncology, Klinikum Esslingen, Hirschlandstraße 97, Esslingen, 73730, Germany.
  • University Clinic for Internal Medicine - Oncology and Hematology, Oldenburg Medical Center, University of Oldenburg, Rahel-Straus-Straße 10, 26133, Oldenburg, Germany.
  • Department of Hematology, Oncology, Infectious Diseases and Palliative Care, Municipal Hospital Karlsruhe, Moltkestraße 90, Karlsruhe, 76133, Germany.
  • Department of Hematology, Oncology and Palliative Care, Hospital Lüdenscheid, Paulmannshöher Str. 14, Lüdenscheid, 58515, Germany.
  • Department of Internal Medicine IV, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, Halle (Saale), 06120, Germany.
  • Department of Internal Medicine III, University Hospital Ulm, Albert-Einstein-Allee 23, Ulm, 89081, Germany.
  • Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg, Hugstetter Straße 55, Freiburg, 79106, Germany.
  • Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg, Hugstetter Straße 55, Freiburg, 79106, Germany.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of the combination of venetoclax (VEN) with azacitidine (AZA) or decitabine (DAC) in the European Union in 2021 for the treatment of patients with newly diagnosed AML who are ineligible for induction chemotherapy has become the treatment backbone for older, medically non-fit AML patients. Based on in vitro priming of AML cells to all-trans retinoic acid (ATRA) by DAC, we had previously conducted a randomized phase II trial (DECIDER, AMLSG 14 - 09) in 200 elderly, non-fit AML patients on the effect of ATRA as add-on to DAC. Median overall survival (OS) was 8.2 months with ATRA versus 5.1 months without ATRA (hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P = 0.006). Notably, ATRA did not add toxicity, the combination was active also in patients with adverse genetics, and prolonged time to treatment resistance. Investigating a triple combination of DAC, VEN and ATRA was a logical next step. This randomized double-blind phase III trial compares the efficacy of ATRA versus placebo as add-on to the backbone treatment (DAC and VEN) with respect to OS, objective best response, quality of life and safety. The accompanying translational research will contribute to identify molecular markers for drug efficacy and better tailoring epigenetic therapy.

METHODS

DECIDER-2 (AMLSG 32 - 21) is a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial. The primary study objective is to compare the efficacy of ATRA versus placebo as add-on to the backbone treatment (DAC and VEN) in terms of OS. The target population is adult AML patients unfit for standard induction chemotherapy. Patients are randomized (1:1) to receive backbone treatment in combination with either ATRA or placebo. Four interim safety analyses were planned with the involvement of the Data Monitoring Committee.

DISCUSSION

This trial investigates whether the in vitro cooperativity of DAC, VEN, and ATRA prolongs OS in unfit AML patients compared to placebo, offering a novel, low-toxicity triplet combination with a promising risk-benefit ratio.

CLINICAL TRIAL NUMBER

EU CT number: 2020-005495-36/2023-507461-26-00 (registered 18.11.2020); German clinical trials registry number: DRKS00023646 (registered 23.08.2022).

MeSH

Safety, Induction Chemotherapy, Neoplasms, Decitabine, Leukemia, Drug Therapy, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Therapeutics, Tretinoin, Chemotherapy