randomized phase iii study of intensive chemotherapy with or without dasatinib (sprycel™)

Conditions: Acute Myeloid Leukemia (AML)

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

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.

Eligibility criteria:
inclusion criteria: * core-binding factor (cbf) aml with molecular diagnosis of runx1-runx1t1 fusion transcript resulting from t(8;21)(q22;q22.1) (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.

Keywords: aml dasatinib core binding factor (cbf)