Combination of Sorafenib With Standard Therapy in Newly Diagnosed Adult CBF AML

Core-binding factor acute myeloid leukemia accounts for 10-15% of AML and is categorized as favorable-risk AML. However, the 5-year CIR was up to 40% in this group of patients. Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML. Sorafenib is a multitargeted TKI, thus the purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Patients must have an unequivocal diagnosis of de novo-CBF AML, prior to start therapy, documented by rearrangement of Core Binding Factor (CBF) genes, namely RUNX1/RUNX1T1 and CBFB/MYH11.
* Age 18 to 65 years old with ECOG performance status 0-2.
* Sign informed consent form, have the ability to comply with study and follow-up procedures.
* Patients must have Total Bilirubin ≤ 1.5 x ULN, and AST or ALT ≤ 2.5 x ULN.
* Patients must have Serum Creatinine ≤ 1.5 x ULN.
* Women of child-bearing potential must have a negative pregnancy test before starting the protocol.

Exclusion Criteria:

* Prior therapy for AML with the following exceptions:

  1. emergency leukapheresis
  2. emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days.
* Central nervous system involvement.
* Presence of any uncontrolled bacterial, viral or fungal infection.
* Known human immunodeficiency virus (HIV) positive.
* An active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
* Presence of other active malignancies.
* QTc \> 470 msec (Bazett formula) on screening ECG.
* Presence of significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:

  1. Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization
  2. History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
  3. Uncontrolled hypertension
  4. Taking medications that are known to be associated with Torsades de Pointes.
* History of hypersensitivity to any drugs or metabolites of similar chemical classes as the study treatment.
* Intolerance to sorafenib, namely persistence of sorafenib-related adverse events despite supportive treatment, persistence or recurrence of adverse events after dose interruption or dose reduction of sorafenib, or both of these.

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