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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-01

Study Completion Date

2023-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Sorafenib to Treat FLT3-ITD AML

NCT02156297

Acute Myeloid Leukemia FLT3-ITD Mutation

UNKNOWN

Study Evaluating Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Less Than 60 Years of Age

NCT00893373

Acute Myeloid Leukemia (AML)

COMPLETED PHASE2

Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

NCT01253070

Acute Myeloid Leukemia With FLT3/ITD Mutation Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 +3 more

COMPLETED PHASE2

Sorafenib and Low Dose Cytarabine in Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT00516828

Leukemia Myelodysplastic Syndromes

COMPLETED PHASE1/PHASE2

Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML

NCT00373373

Acute Myeloid Leukemia

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Core Binding Factor Acute Myeloid Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sorafenib

Induction cycle(s):

IA3+7. Patients will receive sorafenib 400 mg BID on days 8-21.

Consolidation Cycle 1:

IA3+3. Patients will receive sorafenib 400 mg BID on days 1-21.

Consolidation Cycles 2-4:

MDAC. Patients will receive sorafenib 400 mg BID on days 1-21.

Maintenance therapy:

Single agent sorafenib 400 mg BID for one year.

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

Induction cycle(s): 400 mg BID on days 8-21.

Consolidation cycles 1-4: 400 mg BID on days 1-21.

Maintenance therapy: 400 mg BID for one year.

Idarubicin

Intervention Type DRUG

Induction cycle(s): 12 mg/m2/day on days 1-3.

Consolidation cycle 1: 8 mg/m2/day administered on days 1-3.

Cytarabine

Intervention Type DRUG

Induction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7.

Consolidation cycles 1-4: 2 g/m2/12h on days 1-3.

Standard therapy

Induction cycle(s):

IA3+7.

Consolidation Cycle 1:

IA3+3.

Consolidation Cycles 2-4:

MDAC.

Group Type ACTIVE_COMPARATOR

Idarubicin

Intervention Type DRUG

Induction cycle(s): 12 mg/m2/day on days 1-3.

Consolidation cycle 1: 8 mg/m2/day administered on days 1-3.

Cytarabine

Intervention Type DRUG

Induction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7.

Consolidation cycles 1-4: 2 g/m2/12h on days 1-3.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sorafenib

Induction cycle(s): 400 mg BID on days 8-21.

Consolidation cycles 1-4: 400 mg BID on days 1-21.

Maintenance therapy: 400 mg BID for one year.

Intervention Type DRUG

Idarubicin

Induction cycle(s): 12 mg/m2/day on days 1-3.

Consolidation cycle 1: 8 mg/m2/day administered on days 1-3.

Intervention Type DRUG

Cytarabine

Induction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7.

Consolidation cycles 1-4: 2 g/m2/12h on days 1-3.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No