Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)
Conditions
Acute Myeloid Leukemia (AML)
Conditions: official terms
Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
AML, Dasatinib, Core Binding Factor (CBF)
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: Dasatinib Type: Drug
Name: Cytarabine Type: Drug
Name: Daunorubicin Type: Drug
Overall Status
Recruiting
Summary
This is a randomized phase III open-label, multicenter trial evaluating standard induction therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML
Detailed Description
This is a randomized phase III open-label, multicenter trial evaluating standard induction therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML; in the investigational arm, consolidation therapy is followed by a one-year maintenance therapy with dasatinib. Patients with molecular disease persistence or molecular relapse as assessed by quantitative RQ-PCR for the CBF fusion transcripts will be eligible for hematopoietic stem cell transplantation before overt hematologic relapse occurs. Primary endpoint is event-free survival.

AML patients will be assessed for the CBF fusion genes in one of two AMLSG central laboratories within 48 hours of diagnosis, and only patients with CBF-AML will be enrolled.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: 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 (Ulm, Hannover)

- Age ≥ 18; there is no upper age limit

- No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diagnostic 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 potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL with-in 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 contact with women of childbearing potential while taking dasatinib and for 3 months 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

- 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.

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

- Known positive for HIV, active HBV, HCV, or Hepatitis A infection

- Bleeding disorder independent of leukemia

- No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation.

- No consent for biobanking.
Locations
Universitätsklinik für Innere Medizin V
Innsbruck, Austria
Status: Recruiting
Contact: David Nachbaur, Prof. Dr.
Krankenhaus der Barmherzigen Schwestern
Linz, Austria
Status: Recruiting
Contact: Gregor Aschauer, Dr.
Krankenhaus der Elisabethinen Linz GmbH
Linz, Austria
Status: Recruiting
Contact: Sigrid Machherndl-Spandl, Dr.
Universitätsklinik der PMU
Salzburg, Austria
Status: Recruiting
Contact: Richard Greil, Prof.
Hanuschkrankenhaus
Wien, Austria
Status: Recruiting
Contact: Elisabeth Koller, Dr.
MVZ Osthessen
Fulda, Hessen, Germany
Status: Recruiting
Contact: Andrea Distelrath, Dr.
Universitätsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, Germany
Status: Recruiting
Contact: Heinz-August Horst, Prof. Dr.
Helios Klinikum Bad Saarow, Klinik für Hämatologie
Bad Saarow, Germany
Status: Recruiting
Contact: Ulrich Bitz, Dr. med.
Charité Universitätsmedizin Campus Virchow Klinikum
Berlin, Germany
Status: Recruiting
Contact: Jörg Westermann, PD Dr.
Klinikum am Urban
Berlin, Germany
Status: Recruiting
Contact: Christian Scholz, PD Dr.
Klinikum Neukölln
Berlin, Germany
Status: Recruiting
Contact: Maike de Wit, Prof. Dr.
Universitätsklinikum Medizinische Klinik und Poliklinik III
Bonn, Germany
Status: Recruiting
Contact: Karin Mayer, Dr. med.
Städtisches Klinikum Braunschweig gGmbH
Braunschweig, Germany
Status: Recruiting
Contact: Jürgen Krauter, Prof. Dr.
Klinikum Bremen Mitte gGmbH
Bremen, Germany
Status: Recruiting
Contact: Bernd Hertenstein, Prof. Dr.
Klinikum Darmstadt Medizinische Klinik V
Darmstadt, Germany
Status: Recruiting
Contact: Helaga Bernhard, Prof. Dr.
Universitätsklinikum Medizinische Klinik und Poliklinik
Düsseldorf, Germany
Status: Recruiting
Contact: Ulrich Germing, Prof. Dr.
Klinikum Esslingen
Esslingen, Germany
Status: Recruiting
Contact: Carsten Schwänen, PD Dr.
Malteser Krankenhaus St. Franziskus-Hospital
Flensburg, Germany
Status: Recruiting
Contact: Nadezda Basara, Prof. Dr.
Universitätsklinikum Freiburg
Freiburg, Germany
Status: Recruiting
Contact: Michael Lübbert, Prof. Dr.
Wilhelm-Anton-Hospital gGmbH
Goch, Germany
Status: Recruiting
Contact: Volker Runde, Prof. Dr.
Universitätsmedizin Göttingen
Göttingen, Germany
Status: Recruiting
Contact: Gerald Wulf, Prof. Dr.
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Status: Recruiting
Contact: Walter Fiedler, Prof. Dr.
Klinikum Hanau GmbH
Hanau, Germany
Status: Recruiting
Contact: Andrea Sendler, Dr.
Klinikum Region Hannover GmbH
Hannover, Germany
Status: Recruiting
Contact: Hartmut Kirchner, PD Dr.
Medizinische Hochschule Hannover
Hannover, Germany
Status: Recruiting
Contact: Michael Heuser, PD Dr.
SLK-Kliniken GmbH
Heilbronn, Germany
Status: Recruiting
Contact: Uwe Martens, Prof. Dr.
Marienhospital Klinikum der Ruhr-Universität
Herne, Germany
Status: Recruiting
Contact: Beate Schultheis, Dr.
Städtisches Klinikum Karlsruhe gGmbH
Karlsruhe, Germany
Status: Recruiting
Contact: Mark Ringhoffer, PD Dr.
Gemeinschaftspraxis Hämato-Onkologie im Caritas Krankenhaus
Lebach, Germany
Status: Recruiting
Contact: Stephan Kremers, Dr. med.
Klinikum Lippe GmbH
Lemgo, Germany
Status: Recruiting
Contact: Tanja Hesse
Märkische Kliniken GmbH
Lüdenscheid, Germany
Status: Recruiting
Contact: Gerhard Heil, Prof. Dr.
Univ-Klinikum der Otto-von Guericke-Universität
Magdeburg, Germany
Status: Recruiting
Contact: Thomas Heinicke, Dr.
III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität
Mainz, Germany
Status: Recruiting
Contact: Markus Radsak, PD Dr.
Johannes Wesling Klinikum
Minden, Germany
Status: Recruiting
Contact: Hans-Joachim Tischler, Dr.
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany
Status: Recruiting
Contact: Holger Hebart, Prof. Dr.
Klinikum rechts der Isar der TU
München, Germany
Status: Recruiting
Contact: Katharina Götze, PD Dr.
Ortenau Klinikum
Offenburg, Germany
Status: Recruiting
Contact: Andreas Jakob, Dr.
Klinikum Oldenburg gGmbH
Oldenburg, Germany
Status: Recruiting
Contact: Doris Krämer, Prof. Dr.
PIUS Hospital
Oldenburg, Germany
Status: Recruiting
Contact: Frank Griesinger, Prof. Dr.
Klinikum Passau
Passau, Germany
Status: Recruiting
Contact: Thomas Südhoff, Prof. Dr.
Caritasklinkum Saarbrücken St. Theresia
Saarbrücken, Germany
Status: Recruiting
Contact: Axel Matzdorff, Prof. Dr.
Klinikum Stuttgart
Stuttgart, Germany
Status: Recruiting
Contact: Jan Schleicher, Dr.
Vinzenz von Paul Kliniken gGmbH Marienhospital
Stuttgart, Germany
Status: Recruiting
Contact: Claudio Denzlinger, Prof. Dr.
Klinikum Mutterhaus der Borromäerinnen gGmbH
Trier, Germany
Status: Recruiting
Contact: Rolf Mahlenberg, Dr.
Medizinische Universitätsklinik
Tübingen, Germany
Status: Recruiting
Contact: Helmut Salih, Prof. Dr.
Universitätsklinikum Ulm Zentrum für Innere Medizin
Ulm, Germany
Status: Recruiting
Contact: Hartmut Döhner, Prof. Dr.
Schwarzwald-Baar Klinikum
Villingen Schwenningen, Germany
Status: Recruiting
Contact: Wolfram Brugger, Prof.
Kliniken Essen Süd
Werden, Germany
Status: Recruiting
Contact: Mohammed Wattad
HELIOS Klinikum
Wuppertal, Germany
Status: Recruiting
Contact: Silke Schostok, Dr.
Start Date
July 2014
Completion Date
July 2022
Sponsors
University of Ulm
Source
University of Ulm
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page