Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)

Inclusion Criteria:

• Core-binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusiontranscript resulting from t(8;21)(q22;q22.1) (or a variant form) or of CBFB-MYH11fusion transcript resulting from inv(16)(p13.1q22)/t(16;16)(p13.1;q22) as assessed inone 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 thediagnostic screening phase
• Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib inhumans, pregnant or nursing patients may not be enrolled. Women of childbearingpotential (WOCBP) must have a negative serum or urine pregnancy test within asensitivity of at least 25 mIU/mL with-in 72 hours prior to registration. Women ofchild-bearing potential must either commit to continued abstinence from heterosexualintercourse or begin TWO acceptable methods of birth control - one highly effectivemethod (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and oneadditional effective method (e.g., latex condom, diaphragm, or cervical cap) - AT THESAME TIME, at least four weeks before she begins dasatinib therapy. "Women ofchildbearing potential" is defined as a sexually active mature woman who has notundergone a hysterectomy or who has had menses at any time in the preceding 24consecutive months.
• Men must agree not to father a child and must use a latex condom during any sexualcontact with women of childbearing potential while taking dasatinib and for 3 monthsafter 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. Ifedema/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 orrestrictive ventilation disorder)
• Uncontrolled infection
• Patients with a "currently active" second malignancy other than non-melanoma skincancers. Patients are not considered to have a "currently active" malignancy, if theyhave 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 aninformed 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 diseasecharacteristics and course as well as information of the family physician and/or otherphysicians involved in the treatment of the patient about study participation.
• No consent for biobanking.