Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

Condition(s) targeted: Acute Myeloid Leukemia (AML)

Intervention: Dasatinib (Drug); daunorubicin (Drug); Cytarabine (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: University of Ulm

Official(s) and/or principal investigator(s):
Hartmut Doehner, MD, Principal Investigator, Affiliation: University Hospital of Ulm

Overall contact:
Hartmut Doehner, MD, Phone: 004973150045500, Email: hartmut.doehner@uniklinik-ulm.de

This is a Phase Ib/IIa open-labeled multi-center trial evaluating the feasibility of dasatinib given after standard induction therapy with daunorubicin (DNR) and cytarabine (ARA-C), after consolidation therapy with high-dose cytarabine (HDAC), and as single agent in a one-year maintenance therapy in patients with newly diagnosed CBF AML.

25 patients with newly diagnosed CBF AML will be enrolled at AMLSG study centers.

All AML patients will be assessed for the CBF fusion genes via the central laboratory of the AMLSG within 48 hours of diagnosis of AML, and only patients with CBF AML will be enrolled into the study.

Official title: Open-Label, Multicenter Phase Ib/IIa Study For the Evaluation of Dasatinib (Sprycel™) Following Induction and Consolida-tion Therapy as Well as in Maintenance Therapy in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

Study design: Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Feasibility as combined endpoint: Rate of ED/HD Rate of pleural/pericardial effusion grade 3/4 Rate of liver toxicity grade 3/4 that does not improve to <= grade 2 within 14 days after discontinuing responsible medication Rate of refractory disease

Secondary outcome:

Cumulative incidence of relapse (CIR) and death (CID)

Overall survival (os)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Core binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusion

transcript resulting from t(8;21)(q22;q22) (or a variant form) or of CBFB-MYH11 fusion transcript resulting from inv(16)(p13. 1q22)/t(16;16)(p13. 1;q22) as assessed in one of the central AMLSG reference laboratories.

- Age ≥ 18; there is no upper age limit.

- No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the

diag-nostic screening phase.

- Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib

in humans, pregnant or nursing patients may not be enrolled. Women of childbearing poten-tial (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. Women of child-bearing potential must either commit to continued abstinence from heterosexual

intercourse or begin TWO acceptable methods of birth control - one highly effective

method (e. g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one

additional effective method (e. g., latex condom, diaphragm, or cervical cap) - AT THE

SAME TIME, at least four weeks before she begins dasatinib therapy. "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.

- Men must agree not to father a child and must use a latex condom during any sexual

con-tact with women of childbearing potential while taking dasatinib and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy.

- Signed written informed consent

Exclusion Criteria:

- Performance status WHO >2

- Pulmonary edema and/or pleural/pericardial effusion within 14 days of Day 1. If

edema/effusion resolves to CTC Grade ≤ 1, patients can be treated with dasatinib.

- Patients with ejection fraction < 50% by echocardiography within 14 days of day 1

- Organ insufficiency (creatinine >1. 5x upper normal serum level; bilirubin, AST or AP

>2. 5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)

- Uncontrolled infection

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

informed consent

- Known positive for HIV

- Bleeding disorder independent of leukemia

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

disease-characteristics and course

Hartmut Doehner, MD, Phone: 004973150045500, Email: hartmut.doehner@uniklinik-ulm.de

Ubbo-Emmius Klinik Aurich, Aurich 26603, Germany; Recruiting
Dietmar Reichert, MD
Dietmar Reichert, MD, Principal Investigator

Charité Universitätsmedizin Berlin, Berlin 13353, Germany; Recruiting
Joerg Westermann, MD, Phone: 004930450553192, Email: joerg.westermann@charite.de
Joerg Westermann, MD, Principal Investigator

Universitätsklinikum Bonn, Bonn 53105, Germany; Recruiting
von Lilienfeld Marie, MD, Phone: 0049 228-28715507, Email: Marie.v_Lilienfeld-Toal@ukb.uni-bonn.de
Marie von Lilienfeld, MD, Principal Investigator

Städtisches Klinikum Braunschweig, Braunschweig 38114, Germany; Recruiting
Jens Karsten
Jens Karsten, Principal Investigator

Klinikum Bremen-Mitte gGmbH, Bremen 28177, Germany; Recruiting
Bernd Hertenstein, MD, Phone: 0049 421-497-5240, Email: bernd.hertenstein@klinikum-bremen-mitte.de
Bernd Hertenstein, MD, Principal Investigator

Universitätsklinikum Duesseldorf, Duesseldorf 40225, Germany; Recruiting
Andrea Kuendgen, MD, Phone: 0049 211-811778-5/6, Email: kuendgen@med.uni-duesseldorf.de
Andrea Kuendgen, MD, Principal Investigator

Kliniken Essen-Sued, Essen 45239, Germany; Recruiting
Mohammed Wattad, MD, Phone: 020140892233, Email: m.wattad@kliniken-essen-sued.de
Mohammed Wattad, MD, Principal Investigator

Klinikum Esslingen, Esslingen 73730, Germany; Recruiting
Carsten Schwaenen, MD, Phone: +497113103-82460, Email: c.schwaenen@klinikum-esslingen.de
Carsten Schwaenen, MD, Principal Investigator

Städtische Kliniken Frankfurt Höchst, Frankfurt-Höchst 65929, Germany; Recruiting
Hans G Derigs, MD, Email: derigs@skfh.de
Hans G Derigs, MD, Principal Investigator

Medizinische Universitätsklinik, Freiburg 79106, Germany; Recruiting
Michael Luebbert, MD, Phone: 0049 761-270-3534, Email: Michael.luebbert@uniklinik-freiburg.de
Michael Luebbert, MD, Principal Investigator

Medizinisches Versorgungszentrum Osthessen GmbH, Fulda 36043, Germany; Recruiting
Heinz-Gert Höffkes, MD, Phone: 0049 661 84-5481, Email: hoeffkes.tumorklinik@klinikum-fulda.de
Heinz-Gert Höffkes, MD, Principal Investigator

Klinik der Justus Liebig Universität, Gießen 35385, Germany; Active, not recruiting

Wilhelm- Anton- Hospital gGmbH, Goch 47574, Germany; Recruiting
Volker Runde, MD, Phone: 0049 2823-891-115, Email: innere@wilhelm-anton-hospital-goch.de
Volker Runde, MD, Principal Investigator

Universitätsmedizin Göttingen, Göttingen 37075, Germany; Recruiting
Gerald Wulf, MD, Phone: 0049 551-39 12881, Email: gwulf@med.uni-goettingen.de
Gerald Wulf, MD, Principal Investigator

Asklepios Klinik Altona, Hamburg 22763, Germany; Recruiting
Hans-Jürgen Salwender, MD, Phone: +4940-8822-1212, Email: h.salwender@asklepios.com
Hans-Jürgen Salwender, MD, Principal Investigator

Universitätsklinikum Hamburg-Eppendorf, Hamburg 20246, Germany; Recruiting
Walter Fiedler, MD, Phone: +4940-74105 3919, Email: fiedler@uke.uni-hamburg.de
Walter Fiedler, MD, Principal Investigator

Evangelisches Krankenhaus Hamm, Hamm 59063, Germany; Recruiting
Elisabeth Lange, MD, Phone: 0049 2381/589-1211, Email: elange@evkhamm.de
Elisabeth Lange, MD, Principal Investigator

Klinikum Hanau gGmbH, Hanau 63450, Germany; Recruiting
Andrea Sendler, MD, Phone: 0049 6181-296-4345, Email: andrea_sendler@klinikum-hanau.de
Andrea Sendler, MD, Principal Investigator

Medizinische Hochschule Hannover, Hannover 30625, Germany; Recruiting
Juergen Krauter, MD, Phone: 0049 511-532-3720, Email: krauter.juergen@mh-hannover.de
Juergen Krauter, MD, Principal Investigator

Klinikum Hannover Siloah, Hannover 30449, Germany; Recruiting
Hartmut Kirchner, MD, Phone: +49511-927-2801, Email: Hartmut.Kirchner@krh.eu
Hartmut Kirchner, MD, Principal Investigator

SLK-Kliniken Heilbronn GmbH, Heilbronn 74078, Germany; Recruiting
Uwe Martens, MD, Phone: 07131-49-2801, Email: uwe.martens@slk-kliniken.de
Uwe Martens, MD, Principal Investigator

Universitätsklinikum des Saarlandes, Homburg Saar 66424, Germany; Recruiting
Michael Pfreundschuh, MD, Phone: +496841-162-3003, Email: michael.pfreundschuh@uks.eu
Michael Pfreundschuh, MD, Principal Investigator

Staedtisches Klinikum Karlsruhe, Karlsruhe 76133, Germany; Recruiting
Martin Bentz, MD, Phone: 0049 721-974-3000, Email: Martin.Bentz@klinikum-karlsruhe.com
Martin Bentz, MD, Principal Investigator

Staedtisches Krankenhaus Kiel GmbH, Kiel 24116, Germany; Recruiting
Heinz Horst, MD, Phone: 0049 431-1697-1207, Email: h.horst@med2.uni-kiel.de
Heinz Horst, MD, Principal Investigator

Caritas Krankenhaus Lebach, Lebach 66822, Germany; Recruiting
Stephan Kremers, MD, Phone: +496881-501-500, Email: s.kremers@caritas-krankenhaus-lebach.de
Stephan Kremers, MD, Principal Investigator

Klinikum Lippe-Lemgo, Lemgo 32657, Germany; Recruiting
Frank Hartmann, MD, Phone: 0049 52 61 . 26 - 41 22, Email: frank.hartmann@klinikum-lippe.de
Frank Hartmann, MD, Principal Investigator

Klinikum Luedenscheid, Luedenscheid 58515, Germany; Recruiting
Gerhard Heil, MD, Phone: 0049 2351-463541, Email: gerhard.heil@klinikum-luedenscheid.de
Gerhard Heil, MD, Principal Investigator

Univ-Klinikum der Otto- von Guericke- Universität, Magdeburg 39120, Germany; Recruiting
Thomas Heinicke, MD, Phone: +49 391 67 13265, Email: Thomas.Heinicke@med.ovgu.de
Florian Heidel, MD, Principal Investigator

Universitätsklinikum der Johannes Gutenberguniversität Mainz, Mainz 55131, Germany; Recruiting
Wolfgang Herr, MD, Phone: 0049 6131-172710, Email: herr@3-med.klinik.uni-mainz.de
Wolfgang Herr, MD, Principal Investigator

Klinikum rechts der Isar der TU Muenchen, Muenchen 81675, Germany; Recruiting
Katharina Goetze, MD, Phone: 0049 89-4140-5814, Email: K.Goetze@lrz.tum.de
Katharina Goetze, MD, Principal Investigator

klinikum Oldenburg, Oldenburg 26133, Germany; Recruiting
Astrid Schloen, MD, Email: schloen.astrid@klinikum-oldenburg.de
Astrid Schloen, MD, Principal Investigator

Klinikum Passau, Passau 94032, Germany; Recruiting
Thomas Suedhoff, MD, Phone: 0049 851-5300-2356, Email: thomas.suedhoff@klinikum-passau.de
Thomas Suedhoff, MD, Principal Investigator

Elisabeth Krankenhaus, Recklinghausen 45661, Germany; Recruiting
Otto Kloke, MD, Phone: 0049 2361-601-302, Email: dr.kloke@ekonline.de
Otto Kloke, MD, Principal Investigator

Krankenhaus der Barmherzigen Brueder, Regensburg 93049, Germany; Recruiting
Michael Schenk, MD, Phone: 0049 941 3632156
Michael Schenk, MD, Principal Investigator

Akademisches Lehrkrankenhaus des Saarlandes, Saarbrücken 66113, Germany; Recruiting
Axel Matzdorff, MD, Email: a.matzdorff@caritasklinik.de
Axel Matzdorff, MD, Principal Investigator

Klinikverbund Suedwest GmbH, Sindelfingen-Böblingen 71065, Germany; Recruiting
Markus Ritter, Md, Phone: 07031/98-12302, Email: m.ritter@klinikverbund-suedwest.de
Markus Ritter, MD, Principal Investigator

Diakonie-Klinikum Stuttgart, Stuttgart 70176, Germany; Recruiting
Else Heidemann, MD, Phone: 0049 711-991-0 / 3501, Email: heidemann@diak-stuttgart.de
Else Heidemann, MD, Principal Investigator

Klinikum Stuttgart, Stuttgart 70174, Germany; Recruiting
Hans-Guenther Mergenthaler, MD, Phone: 0049 711-278-5601, Email: h.mergenthaler@katharinenhospital.de
Hans-Guenther Mergenthaler, MD, Principal Investigator

Krankenhaus der Barmherzigen Brüder Trier, Trier 54292, Germany; Recruiting
Heinz Kirchen, MD, Email: h.kirchen@bk-trier.de
Heinz Kirchen, MD, Principal Investigator

Medizinische Universitätsklinik Tuebingen, Tuebingen 72076, Germany; Recruiting
Helmut Salih, MD, Phone: 0049 7071-29-83275, Email: helmut.salih@med.uni-tuebingen.de
Helmut Salih, MD, Principal Investigator

Universitätsklinik Ulm, Ulm 89081, Germany; Recruiting
Hartmut Doehner, MD, Phone: 0049 731-50-24400, Email: hartmut.doehner@medizin.uni-ulm.de
Hartmut Doehner, MD, Principal Investigator

Schwarzwald-Baar Klinikum, Villingen-Schwenningen 78050, Germany; Recruiting
Wolfram Brugger, MD, Email: wolfram.brugger@sbk-vs.de
Wolfram Brugger, MD, Principal Investigator

Helios Klinikum Wuppertal, Wuppertal 42283, Germany; Recruiting
Katrin Beckmann, MD
Katrin Beckmann, MD, Principal Investigator

Starting date: June 2009
Last updated: November 3, 2009