Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation
Acute Myeloid Leukemia (AML)
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
AML, NPM1 Mutation, elderly patients (>60 years), unfit for intensive chemotherapy
Study Type
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Cytarabine Type: Drug
Name: Etoposide Type: Drug
Name: All-trans retinoic acid (ATRA) Type: Drug
Overall Status
This is a randomized, Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation ineligible for intensive chemotherapy.

Sample size: 144 patients

Investigator's sites: 50-55 sites in Germany and Austria (2-10 patients per trial site are expected to be included into the trial)

Estimated treatment duration of an individual patient: 8 months (Follow-Up period per patient will last additional 2 years)
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 61 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients with confirmed diagnosis of acute myeloid leukemia according to the World Health Organization (WHO) classification (including de novo AML, t-AML and s-AML)

- Presence of NPM1 mutation as assessed in one of the central AMLSG reference laboratories.

- Age > 60 years. There is no upper age limit.

- No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis if needed for up to 10 days during the diagnostic screening phase.

- Signed written informed consent

- Men must give their informed consent that they do not father a baby and must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy. (while on therapy and for 3 month after the last dose of chemotherapy)

- WHO performance status ≤ 3

- Patients not eligible for intensive chemotherapy according to at least one of the following criteria

- HCT-CI Score >2

- Patient's decision

- age ≥ 75 years

Exclusion Criteria:

The presence of any of the following will exclude a patient from study enrollment:

- All other AML subtypes, in particular those AML with other recurrent genetic changes (according to WHO 2008):

- AML with t(8;21)(q22;q22); RUNX1-RUNX1T1

- AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

- AML with t(15;17)(q22;q12); PML-RARA (or other translocations involving RARA)

- AML with t(9;11)(p22;q23); MLLT3-MLL (or other translocations involving MLL)

- AML with t(6;9)(p23;q34); DEK-NUP214

- AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

- No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician and all other treating physicians about study participation

- Bleeding disorder independent of leukemia

- Uncontrolled infection

- Known positive for HIV, HBV or HCV

- Organ insufficiency (creatinine >1.5x upper normal serum level; bilirubin, AST or ALP >2.5x upper normal serum level, not attributable to AML; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)

- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent

- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
Ubbo-Emmius Klinik Aurich
Aurich, Germany
Status: Recruiting
Contact: Dietmar Reichert, MD
Charité Universitätsmedizin Berlin
Berlin, Germany
Status: Recruiting
Contact: Joerg Westermann, MD - 004930450553192 -
University Hospital of Bonn
Bonn, Germany
Status: Recruiting
Contact: Marie von Lilienfeld-Toal, MD - 014922828714003 -
Städtisches Klinikum Braunschweig
Braunschweig, Germany
Status: Recruiting
Contact: Jens Karsten
Klinikum Bremen-Mitte gGmbH
Bremen, Germany
Status: Recruiting
Contact: Bernd Hertenstein, MD - 0049 421-497-5240 -
Kliniken Essen Süd, Evangelischs Krankenhaus
Essen, Germany
Status: Recruiting
Klinikum Esslingen
Esslingen, Germany
Status: Recruiting
Contact: Carsten Schwaenen, MD - +497113103-82460 -
Medizinische Universitätsklinik
Freiburg, Germany
Status: Recruiting
Contact: Michael Luebbert, MD - 0049 761-270-3534 -
Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, Germany
Status: Recruiting
Contact: Heinz-Gert Höffkes, MD - 0049 661 84-5481 -
Universitätsklinikum Gießen
Gießen, Germany
Status: Recruiting
Wilhelm- Anton- Hospital gGmbH
Goch, Germany
Status: Recruiting
Contact: Volker Runde, MD - 0049 2823-891-115 -
Universitätsmedizin Göttingen
Göttingen, Germany
Status: Recruiting
Contact: Gerald Wulf, MD - 0049 551-39 12881 -
Asklepios Klinik Altona
Hamburg, Germany
Status: Recruiting
Contact: Hans-Jürgen Salwender, MD - +4940-8822-1212 -
University Hospital of Hamburg Eppendorf
Hamburg, Germany
Status: Recruiting
Contact: Walter Fieder, Prof. - 004940428033919 -
Medical Department III, Hospital of Hannover-Siloah
Hannover, Germany
Status: Recruiting
Contact: Hartmut Kirchner, PD Dr. - 0049-511-927- -
Medizinische Hochschule Hannover
Hannover, Germany
Status: Recruiting
Contact: Juergen Krauter, MD - 0049 511-532-3720 -
SLK-Kliniken Heilbronn GmbH
Heilbronn, Germany
Status: Recruiting
Contact: Uwe Martens, MD - 07131-49-2801 -
Department of Internal Medicine I, University Hospital of Saarland
Homburg, Germany
Status: Recruiting
Contact: Michael Pfreundschuh, Prof. Dr. - +49 (0) 6841-162-3084 -
Staedtisches Klinikum Karlsruhe
Karlsruhe, Germany
Status: Recruiting
Contact: Martin Bentz, MD - 0049 721-974-3000 -
Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach
Lebach, Germany
Status: Recruiting
Contact: Stephan Kremers, Dr. - +49 (0)6881-501-217 -
Klinikum der Johannes Gutenberg Universität Mainz
Mainz, Germany
Status: Recruiting
Klinikum rechts der Isar der TU Muenchen
Muenchen, Germany
Status: Recruiting
Contact: Katharina Goetze, MD - 0049 89-4140-5814 -
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany
Status: Recruiting
Pius Hospital Oldenburg
Oldenburg, Germany
Status: Recruiting
Contact: Frank Griesinger, MD
Krankenhaus der Barmherzigen Brueder
Regensburg, Germany
Status: Recruiting
Contact: Michael Schenk, MD - 0049 941 3632156
Caritas-Klinik St. Theresia
Saarbrücken, Germany
Status: Recruiting
Contact: Axel Matzdorff, MD -
Clinikal Cetner of Stuttgart, Center of Oncology
Stuttgart, Germany
Status: Recruiting
Contact: Hans-Günther Mergenthaler, Prof. Dr. - +49 (0) 711-278-5601 -
Diakonie-Klinikum Stuttgart
Stuttgart, Germany
Status: Recruiting
Contact: Else Heidemann, MD - 0049 711-991-0 / 3501 -
Krankenhaus der Barmherzigen Brüder Trier
Trier, Germany
Status: Recruiting
Contact: Heinz Kirchen, MD -
Universitätsklinikum Tübingen
Tübingen, Germany
Status: Recruiting
University hospital of Ulm
Ulm, Germany
Status: Recruiting
Contact: Richard F Schlenk, MD
Medical Center II - Hematology/Oncology, Clinical Center Villingen-Schwenningen
Villingen - Schwenningen, Germany
Status: Recruiting
Contact: Wolfram Brugger, Prof. Dr. - +49 (0) 7721-93-4001 -
Helios Klinikum Wuppertal
Wuppertal, Germany
Status: Recruiting
Contact: Katrin Beckmann, MD
Start Date
March 2011
Completion Date
December 2018
University of Ulm
University of Ulm
Record processing date processed this data on July 28, 2015 page