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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    88
  • sponsor
    Nanfang Hospital of Southern Medical University
Updated on 17 June 2022

Summary

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.

Description

Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and accounts for 10-15% of AML. Because of the high CR rate of nearly 90% and a 5-year OS of almost 50%, CBF-AML is categorized as favorable-risk AML. However, the 5-year cumulative incidence of relapse (CIR) was up to 40% in this group of patients after high-dose cytarabine consolidation following CR. Therefore, more effective therapeutic approaches are needed.

Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML likely result in aberrant tyrosine kinase activity, leukemia cell growth and survival, and treatment resistance. Thus, pharmacologic inhibition of KIT would lead to significant antileukemia activity if combined with an optimized chemotherapy regimen in patients with CBF AML. Recent mechanistic findings also support the potential clinical benefit of KIT inhibition in CBF AML.

Sorafenib is a first-generation type-II multitargeted tyrosine kinase receptor inhibitor (TKI) that suppresses various signaling pathways associated with the development of AML, such as RTK (FLT3, c-KIT), RAS/RAF, vascular endothelial growth factor (VEGF) receptor. The purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.

Details
Condition Core Binding Factor Acute Myeloid Leukemia
Treatment cytarabine, Idarubicin, Sorafenib
Clinical Study IdentifierNCT05404516
SponsorNanfang Hospital of Southern Medical University
Last Modified on17 June 2022

Eligibility

Yes No Not Sure

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
emergency leukapheresis
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
Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization
History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
Uncontrolled hypertension
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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