Clinical trial NCT00850382: Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: CBF AML
Dasatinib
Core Binding Factor (CBF)
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2009-02-25
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

82 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.


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: after 4 weeks
Secondary outcomes:
measure: Cumulative incidence of relapse (CIR) and death (CID)
timeFrame: After follow-up period of two years
measure: Overall survival (os)
timeFrame: After follow-up period of two years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinikum Innsbruck
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern
city: Linz
country: Austria
facility: Elisabethinen Krankenhaus
city: Salzburg
country: Austria
facility: Landeskliniken Salzburg
city: Wien
country: Austria
facility: Hanuschkrankenhaus Wien
city: Aurich
country: Germany
facility: Ubbo-Emmius Klinik Aurich
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Duesseldorf
country: Germany
facility: Universitätsklinikum Duesseldorf
city: Essen
country: Germany
facility: Kliniken Essen-Sued
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Frankfurt-Höchst
country: Germany
facility: Städtische Kliniken Frankfurt Höchst
city: Freiburg
country: Germany
facility: Medizinische Universitätsklinik
city: Fulda
country: Germany
facility: Medizinisches Versorgungszentrum Osthessen GmbH
city: Gießen
country: Germany
facility: Klinik der Justus Liebig Universität
city: Goch
country: Germany
facility: Wilhelm- Anton- Hospital gGmbH
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm
city: Hanau
country: Germany
facility: Klinikum Hanau gGmbH
city: Hannover
country: Germany
facility: Klinikum Hannover Siloah
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Homburg Saar
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe
city: Kiel
country: Germany
facility: Staedtisches Krankenhaus Kiel GmbH
city: Lebach
country: Germany
facility: Caritas Krankenhaus Lebach
city: Lemgo
country: Germany
facility: Klinikum Lippe-Lemgo
city: Luedenscheid
country: Germany
facility: Klinikum Luedenscheid
city: Magdeburg
country: Germany
facility: Univ-Klinikum der Otto- von Guericke- Universität
city: Mainz
country: Germany
facility: Universitätsklinikum der Johannes Gutenberguniversität Mainz
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Passau
country: Germany
facility: Klinikum Passau
city: Recklinghausen
country: Germany
facility: Elisabeth Krankenhaus
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brueder
city: Saarbrücken
country: Germany
facility: Caritas-Klinik St. Theresia
city: Sindelfingen
country: Germany
facility: Klinikum Sindelfingen-Böblingen
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Diakonie-Klinikum Stuttgart
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Tuebingen
country: Germany
facility: Medizinische Universitätsklinik Tuebingen
city: Ulm
country: Germany
facility: Universitätsklinik Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
Study officials:
affiliation: University Hospital of Ulm
name: Hartmut Doehner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lubbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kundgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwanen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Gohring G, Ganser A, Dohner K, Dohner H. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial. Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.