Study on All-Trans Retinoic Acid, Induction and Consolidation Therapy, and Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

Condition(s) targeted: Acute Myeloid Leukemia

Intervention: Cytarabine (Drug); Idarubicin (Drug); Etoposide (Drug); All-trans retinoic acid (Drug); Pegfilgrastim (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of Ulm

Official(s) and/or principal investigator(s):
Richard F Schlenk, Dr., Principal Investigator, Affiliation: Department of Internal Medicine III, University of Ulm

Overall contact:
Richard F Schlenk, Dr., Phone: 0049-(0)731-500-, Ext: 45900, Email: richard.schlenk@uniklinik-ulm.de

This trial is a study on all-trans retinoic acid in combination with induction and consolidation therapy as well as pegfilgrastim after consolidation therapy in younger patients with newly diagnosed acute myeloid leukemia (AML).

Official title: Randomized Phase II/III-Study on All-Trans Retinoic Acid in Combination With Induction and Consolidation Therapy as Well as Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Complete remission (CR)-rate after induction therapy

Relapse-free survival, one year after consolidation therapy with high-dose cytarabine considering different temporal sequences (1-3-5 versus 1-2-3) of the consolidation therapy

Event-free survival

Secondary outcome:

Kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs

Cumulative incidence of relapse

Cumulative incidence of death

Overall survival

Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle

Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle

Hematologic and non-hematologic toxicity after consolidation therapy with high-dose cytarabine considering the different consolidation schemes (day 1-3-5 versus day 1-2-3)

Days in hospital after each consolidation cycle

Detailed description: First Induction Therapy:

- Cytarabine 100 mg/m² cont. i. v. days 1-7

- Idarubicin 12 mg/m² i. v. days 1,3,5

- Etoposide 100 mg/m² i. v. days 1-3

- ± ATRA 45 mg/m² p. o. days 6-8

- ATRA 15 mg/m² p. o. days 9-21

Second Induction Therapy:

- Cytarabine 100 mg/m² cont. i. v. days 1-7

- Idarubicin 12 mg/m² i. v. days 1 and 3

- Etoposide 100 mg/m² i. v. days 1-3

- ± ATRA 45 mg/m² p. o. days 6-8

- ATRA 15 mg/m² p. o. days 9-21

Consolidation Therapy:

cohort 1 (<= ID 336)

- Cytarabine 3 g/m² 2x/die i. v. Tag 1,3,5

- ± ATRA 15 mg/m² p. o. Tag 6-21

- Pegfilgrastim 6 mg s. c day 10

cohort 2 (> ID 336)

- Cytarabine 3 g/m² 2x/die i. v. Tag 1,2,3

- ± ATRA 15 mg/m² p. o. Tag 4-21

- Pegfilgrastim 6 mg s. c day 8

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Newly diagnosed AML defined according to the World Health Organization

(WHO)-classification (excluding acute promyelocytic leukemia [APL])

- Ages 18-60 years

- Written informed consent of each patient at study entry.

- Molecular and cytogenetical diagnostics on initial bone marrow and peripheral blood

specimen at the central reference laboratories

Exclusion Criteria:

- Bleeding independent of the AML

- Acute promyelocytic leukemia

- Uncontrollable infection

- Participation in a concurrent clinical study

- Insufficiency of the kidneys (creatinine > 1. 5x upper normal serum level), of the

liver (bilirubin, AST or AP > 2x upper normal serum level), severe obstructive or restrictive ventilation disorder, heart failure New York Heart Association (NYHA) III/IV

- Severe neurological or psychiatric disorder interfering with ability to give an

informed consent.

- No consent for registration, storage and processing of the individual

disease-characteristics and course.

- Performance status WHO > 2

- Pregnancy

Richard F Schlenk, Dr., Phone: 0049-(0)731-500-, Ext: 45900, Email: richard.schlenk@uniklinik-ulm.de

Department of Hematology/Oncology, University Hospital Innsbruck, Innsbruck 6020, Austria; Recruiting
David Nachbaur, Prof. Dr., Phone: 0043-650-8709121, Ext: 23338
David Nachbaur, Prof. Dr., Principal Investigator

Department of Internal Medicine I, Krankenhaus der Barmherzigen Schwestern, Linz 4010, Austria; Recruiting
Andreas Petzer, Prof. Dr., Phone: +43- 732 -7677 -, Ext: 7345, Email: andreas.petzer@bhs.at
Andreas Petzer, Prof. Dr., Principal Investigator

Medical Department III, St. Johann-Hospital, Salzburg 5020, Austria; Recruiting
R. Greil, Prof. Dr., Phone: +43-662-4482-, Ext: 2879, Email: R.Greil@salk.at
R. Greil, Prof. Dr., Principal Investigator

Center of Hematology and Oncology, Hanusch-Hospital, Wien 1140, Austria; Recruiting
Elisabeth Pittermann-Höcker, Prim. Dr., Phone: +43 01-91021-, Ext: 85411, Email: elisabeth.pittermann-hoecker@wgkk.sozvers.at
Elisabeth Pittermann-Höcker, Prim. Dr., Principal Investigator

Department of General Internal Medicine, University Hospital of Bonn, Bonn 53127, Germany; Recruiting
Ingo Schmidt-Wolf, Prof. Dr., Phone: 0049-(0)228-287, Ext: 6816, Email: Ingo.schmidt-wolf@ukb.uni-bonn.dede
Ingo Schmidt-Wolf, Prof. Dr., Principal Investigator

Clinical Center of Hematology and Oncology, University Hospital of Düsseldorf, Düsseldorf 40225, Germany; Recruiting
Ulrich Germing, PD Dr., Phone: +49 (0) 211-811-7780, Ext: 8853, Email: germing@med.uni-duesseldorf.de
Ulrich Germing, PD Dr., Principal Investigator

Department of Hematology and Oncology, Hospital Essen Süd, Ev. Hospital of Essen-Werden, Essen 45239, Germany; Recruiting
Wolfgang Heit, Prof. Dr., Phone: +49 (0) 201-4089-2231, Ext: 2297, Email: w.heit.medk@kliniken-essen-sued.de
Wolfgang Heit, Prof. Dr., Principal Investigator

Medical Department III, Hematology/Oncology, University of Frankfurt, Frankfurt 60590, Germany; Recruiting
Dieter Hölzer, Prof. Dr., Phone: +49 (0) 69-6301-5194, Ext: 7326, Email: hoelzer@em.uni-frankfurt.de
Dieter Hölzer, Prof. Dr., Principal Investigator

Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst, Frankfurt 65929, Germany; Recruiting
Hans-Günther Derigs, Prof. Dr., Phone: +49 (0) 69-3106-3320, Ext: 3280, Email: derigs@skfh.de
Hans-Günther Derigs, Prof. Dr., Principal Investigator

Internal Medicine I, University of Freiburg, Freiburg 79106, Germany; Recruiting
Michael Lübbert, Prof. Dr., Phone: +49 (0) 761-270-3401, Ext: 3697, Email: luebbert@mm11.ukl.uni-freiburg.de
Michael Lübbert, Prof. Dr., Principal Investigator

Medical Department IV, University Hospital of Giessen, Giessen 35392, Germany; Recruiting
Mathias Rummel, PD Dr., Email: mathias.rummel@innere.med.uni-giessen.de
Mathias Rummel, PD Dr., Principal Investigator

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH, Goch 47574, Germany; Recruiting
Volker Runde, Prof. Dr., Phone: +49 (0) 2823-891-115, Ext: 322, Email: innere@wilhelm-anton-hospital-goch.de
Volker Runde, Prof. Dr., Principal Investigator

Centre of Internal Medicine, University Hospital Göttingen, Göttingen 37075, Germany; Recruiting
Lorenz Trümper, Prof. Dr., Phone: +49 (0) 551-39-8535, Ext: 8587, Email: lorenz.truemper@med.uni-goettingen.de
Lorenz Trümper, Prof. Dr., Principal Investigator

Medical Department II, Hematology and Oncology, General Hospital Altona, Hamburg 22763, Germany; Recruiting
Hans Salwender, Dr., Phone: +49 (0) 40-8822-1212, Ext: 4904, Email: salwender@web.de
Hans Salwender, Dr., Principal Investigator

Department of Oncology and Hematology, University Hospital Eppendorf, Hamburg 20246, Germany; Recruiting
Carsten Bokemeyer, Prof. Dr., Phone: +49 (0) 40 / 42803 - 2960, Ext: 8054, Email: c.bokemeyer@uke.uni-hamburg.de
Carsten Bokemeyer, Prof. Dr., Principal Investigator

Medical Department III, Clinical Center Hanau, Hanau 63450, Germany; Recruiting
Andrea Sendler, Dr., Phone: +49 (0) 6181-296-4345, Ext: 4309, Email: andrea_sendler@klinikum-hanau.de
Andrea Sendler, Dr., Principal Investigator

Department of Hematology, Hematology and Oncology, Medizinische Hochschule Hannover, Hannover 30625, Germany; Recruiting
Arnold Ganser, Prof. Dr., Phone: +49 (0) 511-532-5112, Ext: 8041, Email: ganser.arnold@mh-hannover.de
Arnold Ganser, Prof. Dr., Principal Investigator

Department of Internal Medicine I, University Hospital of Saarland, Homburg 66421, Germany; Recruiting
Michael Pfreundschuh, Prof. Dr., Phone: +49 (0) 6841-162-3084, Ext: 3031, Email: michael.pfreundschuh@uniklinik-saarland.de
Michael Pfreundschuh, Prof. Dr., Principal Investigator

Medical Department II, City Hospital Karlsruhe gGmbH, Karlsruhe 76133, Germany; Recruiting
Martin Bentz, Prof. Dr., Phone: +49 (0) 721-974-3000, Ext: 3009, Email: Martin.Bentz@klinikum-karlsruhe.com
Martin Bentz, Prof. Dr., Principal Investigator

Medical Department II, University Hospital of Kiel, Kiel 24116, Germany; Recruiting
H.-A. Horst, PD Dr., Phone: +49 (0) 431-1697-1207, Ext: 1202, Email: h.horst@med2.uni-kiel.de
H.-A. Horst, PD Dr., Principal Investigator

Department of Internal Medicine/Hematology and Oncology, Cartias Hospital Lebach, Lebach 66822, Germany; Recruiting
Stephan Kremers, Dr., Phone: +49 (0) 6881-501-217, Ext: 153, Email: s.kremers@caritas-krankenhaus-lebach.de
Stephan Kremers, Dr., Principal Investigator

Department of Hematology and Internal Oncology, University Hospital of Mainz, Mainz 55101, Germany; Recruiting
Matthias Theobald, Prof. Dr., Phone: +49 (0) 6131-175047, Ext: 3933364, Email: m.theobald@3-med.klinik.uni-mainz.de
Matthias Theobald, Prof. Dr., Principal Investigator

Medical Department III, Clinical Center Rechts der Isar, München 81675, Germany; Recruiting
Christian Peschel, Prof. Dr., Phone: +49 (0) 89-4140-4111, Ext: 4809, Email: christian.peschel@lrz.tum.de
Christian Peschel, Prof. Dr., Principal Investigator

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH, Oldenburg 26133, Germany; Recruiting
Francesco del Valle, Dr., Phone: +49 (0) 441-403-2615, Ext: 2892, Email: delvalle.f@klinikum-oldenburg.de
Francesco del Valle, Dr., Principal Investigator

Department of Hematology and Oncology, Caritas Hospital St. Theresia, Saarbrücken 66113, Germany; Recruiting
Axel Matzdorff, PD Dr., Phone: +49 (0) 681-406-1104, Email: a.matzdorff@caritasklinik.de
Axel Matzdorff, PD Dr., Principal Investigator

Department of Oncology, Clinical Center of Stuttgart, Stuttgart 70174, Germany; Recruiting
Hans-Günther Mergenthaler, Prof. Dr., Phone: +49 (0) 711-278-5601, Ext: 5609, Email: h.mergenthaler@katharinenhospital.de
Hans-Günther Mergenthaler, Prof. Dr., Principal Investigator

Medical Department I, Hospital of Barmherzige Brüder, Trier 54292, Germany; Recruiting
Heinz Kirchen, Dr., Phone: +49 (0) 651-2080, Ext: 2678, Email: h.kirchen@bk-trier.de
Heinz Kirchen, Dr., Principal Investigator

Department of Internal Medicine II, University Hospital of Tübingen, Tübingen 72076, Germany; Recruiting
Peter Brossart, PD Dr., Phone: 49+ (0)7071-29-80625, Ext: 5709, Email: peter.brossart@med.uni-tuebingen.de
Peter Brossart, PD Dr., Principal Investigator

Medical Clinic II-Hematology/Oncology, Hospital Villingen-Schwenningen, Villingen-Schwenningen 78050, Germany; Recruiting
Wolfram Brugger, Prof. Dr., Phone: +49 (0) 7721-93-4001, Ext: 4099, Email: imo.wolfram.brugger@klinikumvs.de
Wolfram Brugger, Prof. Dr., Principal Investigator

Medical Department I, Helios Hospital Wuppertal, Wuppertal 42283, Germany; Recruiting
Aruna Raghavachar, PD Dr., Phone: +49 (0) 202-896-3351, Ext: 2739, Email: araghavachar@wuppertal.helios-kliniken.de
Aruna Raghavachar, PD Dr., Principal Investigator

Medical Department I, Hospital Bremen-Mitte, Bremen 28177, Germany; Recruiting
Bernd Hertenstein, Prof. Dr., Phone: 0049-(0)421-497-, Ext: 5240, Email: bernd.hertenstein@klinikum-bremen-mitte.de
Bernd Hertenstein, Prof. Dr., Principal Investigator

Medical Department III, Hospital Hannover-Siloah, Hannover 30449, Germany; Recruiting
Hartmut Kirchner, PD Dr., Phone: 0049-(0)511-927-, Ext: 2801, Email: Hartmut.Kirchner.Siloah@krh.eu
Hartmut Kirchner, PD Dr., Principal Investigator

Department of Hematology and Oncology, Hospital of Lüdenscheid, Lüdenscheid 58505, Germany; Recruiting
Gerhard Heil, Prof. Dr., Phone: 0049-(0)2351-46, Ext: 3541, Email: gerhard.heil@klinikum-luedenscheid.de
Gerhard Heil, Prof. Dr., Principal Investigator

Medical Department II, Diakonie Hospital, Stuttgart 70176, Germany; Recruiting
Else Heidemann, Prof. Dr., Phone: 0049-(0)711-991-0, Email: heidemann@diak-stuttgart.de
Else Heidemann, Prof. Dr., Principal Investigator

AMLSG Study Office, Department of Internal Medicine III, University of Ulm

Starting date: July 2004
Ending date: September 2010
Last updated: June 25, 2008