Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)
- Conditions
- Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT00850382
- Lead Sponsor
- University of Ulm
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 89
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dasatinib Dasatinib Induction cycle(s): Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle. Consolidation Cycles 1, 2, 3, 4: Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse). Dasatinib daunorubicin Induction cycle(s): Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle. Consolidation Cycles 1, 2, 3, 4: Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse). Dasatinib Cytarabine Induction cycle(s): Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle. Consolidation Cycles 1, 2, 3, 4: Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).
- Primary Outcome Measures
Name Time Method 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 after 4 weeks
- Secondary Outcome Measures
Name Time Method Cumulative incidence of relapse (CIR) and death (CID) After follow-up period of two years Overall survival (os) After follow-up period of two years
Trial Locations
- Locations (50)
Krankenhaus der Barmherzigen Schwestern
🇦🇹Linz, Austria
Elisabethinen Krankenhaus
🇦🇹Linz, Austria
Universitätsklinikum Innsbruck
🇦🇹Innsbruck, Austria
Ubbo-Emmius Klinik Aurich
🇩🇪Aurich, Germany
Landeskliniken Salzburg
🇦🇹Salzburg, Austria
Hanuschkrankenhaus Wien
🇦🇹Wien, Austria
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Städtisches Klinikum Braunschweig
🇩🇪Braunschweig, Germany
Klinikum Bremen-Mitte gGmbH
🇩🇪Bremen, Germany
Städtische Kliniken Frankfurt Höchst
🇩🇪Frankfurt-Höchst, Germany
Klinikum Darmstadt
🇩🇪Darmstadt, Germany
Klinikum Esslingen
🇩🇪Esslingen, Germany
Universitätsklinikum Duesseldorf
🇩🇪Duesseldorf, Germany
Kliniken Essen-Sued
🇩🇪Essen, Germany
Medizinische Universitätsklinik
🇩🇪Freiburg, Germany
Wilhelm- Anton- Hospital gGmbH
🇩🇪Goch, Germany
Medizinisches Versorgungszentrum Osthessen GmbH
🇩🇪Fulda, Germany
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Klinik der Justus Liebig Universität
🇩🇪Gießen, Germany
Evangelisches Krankenhaus Hamm
🇩🇪Hamm, Germany
Klinikum Hanau gGmbH
🇩🇪Hanau, Germany
Klinikum Hannover Siloah
🇩🇪Hannover, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg Saar, Germany
Staedtisches Klinikum Karlsruhe
🇩🇪Karlsruhe, Germany
Staedtisches Krankenhaus Kiel GmbH
🇩🇪Kiel, Germany
Klinikum Lippe-Lemgo
🇩🇪Lemgo, Germany
Caritas Krankenhaus Lebach
🇩🇪Lebach, Germany
Klinikum Luedenscheid
🇩🇪Luedenscheid, Germany
Univ-Klinikum der Otto- von Guericke- Universität
🇩🇪Magdeburg, Germany
Johannes Wesling Klinikum
🇩🇪Minden, Germany
Universitätsklinikum der Johannes Gutenberguniversität Mainz
🇩🇪Mainz, Germany
Klinikum rechts der Isar der TU Muenchen
🇩🇪Muenchen, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Klinikum Passau
🇩🇪Passau, Germany
Elisabeth Krankenhaus
🇩🇪Recklinghausen, Germany
Krankenhaus der Barmherzigen Brueder
🇩🇪Regensburg, Germany
Caritas-Klinik St. Theresia
🇩🇪Saarbrücken, Germany
Klinikum Sindelfingen-Böblingen
🇩🇪Sindelfingen, Germany
Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Krankenhaus der Barmherzigen Brüder Trier
🇩🇪Trier, Germany
Diakonie-Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Medizinische Universitätsklinik Tuebingen
🇩🇪Tuebingen, Germany
Universitätsklinik Ulm
🇩🇪Ulm, Germany
Schwarzwald-Baar Klinikum
🇩🇪Villingen-Schwenningen, Germany
Helios Klinikum Wuppertal
🇩🇪Wuppertal, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany