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
Conditions
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
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cytarabine Type: Drug
Name: Etoposide Type: Drug
Name: All-trans retinoic acid (ATRA) Type: Drug
Overall Status
Recruiting
Summary
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.
Locations
Ubbo-Emmius Klinik Aurich
Aurich, Germany
Status: Recruiting
Contact: Dietmar Reichert, MD
Charité Universitätsmedizin Berlin
Berlin, Germany
Status: Recruiting
Contact: Joerg Westermann, MD - 004930450553192 - joerg.westermann@charite.de
University Hospital of Bonn
Bonn, Germany
Status: Recruiting
Contact: Marie von Lilienfeld-Toal, MD - 014922828714003 - m.lilienfeld.toal@uni-bonn.de
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 - bernd.hertenstein@klinikum-bremen-mitte.de
Kliniken Essen Süd, Evangelischs Krankenhaus
Essen, Germany
Status: Recruiting
Klinikum Esslingen
Esslingen, Germany
Status: Recruiting
Contact: Carsten Schwaenen, MD - +497113103-82460 - c.schwaenen@klinikum-esslingen.de
Medizinische Universitätsklinik
Freiburg, Germany
Status: Recruiting
Contact: Michael Luebbert, MD - 0049 761-270-3534 - Michael.luebbert@uniklinik-freiburg.de
Medizinisches Versorgungszentrum Osthessen GmbH
Fulda, Germany
Status: Recruiting
Contact: Heinz-Gert Höffkes, MD - 0049 661 84-5481 - hoeffkes.tumorklinik@klinikum-fulda.de
Universitätsklinikum Gießen
Gießen, Germany
Status: Recruiting
Wilhelm- Anton- Hospital gGmbH
Goch, Germany
Status: Recruiting
Contact: Volker Runde, MD - 0049 2823-891-115 - innere@wilhelm-anton-hospital-goch.de
Universitätsmedizin Göttingen
Göttingen, Germany
Status: Recruiting
Contact: Gerald Wulf, MD - 0049 551-39 12881 - gwulf@med.uni-goettingen.de
Asklepios Klinik Altona
Hamburg, Germany
Status: Recruiting
Contact: Hans-Jürgen Salwender, MD - +4940-8822-1212 - h.salwender@asklepios.com
University Hospital of Hamburg Eppendorf
Hamburg, Germany
Status: Recruiting
Contact: Walter Fieder, Prof. - 004940428033919 - fiedler@uke.uni-hamburg.de
Medical Department III, Hospital of Hannover-Siloah
Hannover, Germany
Status: Recruiting
Contact: Hartmut Kirchner, PD Dr. - 0049-511-927- - Hartmut.Kirchner.Siloah@krh.eu
Medizinische Hochschule Hannover
Hannover, Germany
Status: Recruiting
Contact: Juergen Krauter, MD - 0049 511-532-3720 - krauter.juergen@mh-hannover.de
SLK-Kliniken Heilbronn GmbH
Heilbronn, Germany
Status: Recruiting
Contact: Uwe Martens, MD - 07131-49-2801 - uwe.martens@slk-kliniken.de
Department of Internal Medicine I, University Hospital of Saarland
Homburg, Germany
Status: Recruiting
Contact: Michael Pfreundschuh, Prof. Dr. - +49 (0) 6841-162-3084 - michael.pfreundschuh@uniklinik-saarland.de
Staedtisches Klinikum Karlsruhe
Karlsruhe, Germany
Status: Recruiting
Contact: Martin Bentz, MD - 0049 721-974-3000 - Martin.Bentz@klinikum-karlsruhe.com
Department of Interial Medicine /Hematology and Oncology, Caritas Hospital Lebach
Lebach, Germany
Status: Recruiting
Contact: Stephan Kremers, Dr. - +49 (0)6881-501-217 - s.kremers@caritas-krankenhaus-lebach.de
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 - K.Goetze@lrz.tum.de
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 - a.matzdorff@caritasklinik.de
Clinikal Cetner of Stuttgart, Center of Oncology
Stuttgart, Germany
Status: Recruiting
Contact: Hans-Günther Mergenthaler, Prof. Dr. - +49 (0) 711-278-5601 - h.mergenthaler@katharinenhospital.de
Diakonie-Klinikum Stuttgart
Stuttgart, Germany
Status: Recruiting
Contact: Else Heidemann, MD - 0049 711-991-0 / 3501 - heidemann@diak-stuttgart.de
Krankenhaus der Barmherzigen Brüder Trier
Trier, Germany
Status: Recruiting
Contact: Heinz Kirchen, MD - h.kirchen@bk-trier.de
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 - imo.wolfram.brugger@klinikumvs.de
Helios Klinikum Wuppertal
Wuppertal, Germany
Status: Recruiting
Contact: Katrin Beckmann, MD
Start Date
March 2011
Completion Date
December 2018
Sponsors
University of Ulm
Source
University of Ulm
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page