Randomized Phase III Study of Intensive Chemotherapy with or without Dasatinib (Sprycel™) in Adult Patients with Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)
- Conditions
- ewly Diagnosed Core-Binding FactorAcute Myeloid Leukemia (CBF-AML)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2013-003117-18-AT
- Lead Sponsor
- niversitätsklinikum Ulm
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 203
•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 la-boratories (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 contin-ued 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 until at least 3 months after last dasatinib administration. 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 preced-ing 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 193
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
•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 or MUGA 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. Pa-tients 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML;Secondary Objective: •To assess the interaction between type of CBF-AML [t(8;21) versus inv(16)] and randomization accordingly on all survival endpoints<br>•To assess cumulative incidence of relapse (CIR) and death (CID)<br>•To assess relapse-free (RFS) and overall survival (OS)<br>•To assess outcome according to KIT mutational status<br>•To assess pharmacodynamic inhibition of KIT <br>•To assess toxicity<br>;Primary end point(s): •Event-free survival (EFS);Timepoint(s) of evaluation of this end point: The primary endpoint of the study, EFS rate, will be evaluated<br>after 4 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Cumulative incidence of relapse (CIR) and death CID)<br>•Relapse-free (RFS) and overall survival (OS)<br>•Outcome of patients according to KIT mutational status<br>•Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)<br><br>Safety endpoints: <br>•Rate of early (ED)/ hypoplastic (HD) deaths<br>•Type, frequency, severity (graded using the National Cancer Institute Common Terminology Crite-ria for Adverse Events [NCI CTCAE] version 4.03), timing and relatedness of non-hematologic toxicity observed during different treatment cycles.<br>;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analyzed at the same time point as the<br>primary endpoint in an exploratory manner.