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

Study Overview
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Brief Summary
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The primary purpose of the study is to determine, whether the addition of Sorafenib to standard chemotherapy in elderly patients with newly diagnosed AML improves treatment results (event free survival).

Official Title
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A Double-blind, Placebo-controlled, Randomized, Multi-center Phase II Trial to Assess the Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Sorafenib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed AML (except APL) according to the FAB and WHO classification, including AML evolving from MDS or other hematologic diseases and AML after previous cytotoxic therapy or radiation (secondary AML) Bone marrow aspirate or biopsy must contain >= 20% blasts of all nucleated cells, with the exception of AML FAB M6, where >= 30% of non-erythroid cells must be leukemic blasts Age >= 61 years Informed consent, personally signed and dated to participate in the study Male patients enrolled in this trial must use adequate barrier birth control measures during the course of the Sorafenib treatment and for at least 3 months after the last administration of Sorafenib Exclusion Criteria: Central nervous system manifestation of AML Cardiac Disease: Heart failure NYHA III° or IV°; active coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) Chronically impaired renal function (creatinin clearance < 30 ml/min) Chronic pulmonary disease with relevant hypoxia Inadequate liver function (ALT and AST >= 2.5 x ULN) Total bilirubin >= 1.5 x ULN Resting blood pressure (BP) consistently higher than systolic 160 mmHg and/or diastolic 95 mmHg Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardise compliance with the protocol Uncontrolled active infection Concurrent malignancies other than AML Previous treatment of AML except hydroxyurea and up to 2 days <= 100 mg/m²/d cytarabine Known HIV and/or hepatitis C infection Evidence or history of CNS disease, including primary or metastatic brain tumors, seizure disorders Thrombotic or embolic events such as cerebrovascular accident or pulmonary embolism within 1 year of study entry Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy History of organ allograft Concomitant treatment with kinase inhibitors, angiogenesis inhibitors and Myelotarg Patients with major surgery, open biopsy or significant traumatic injury within 4 weeks of start or first dose Serious, non-healing wound, ulcer or bone fracture Allergy to study medication or excipients in study medication Investigational drug therapy outside of this trial during or within 4 weeks of study entry Patients who are not eligible for standard chemotherapy

Ages Eligible for Study
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Minimum Age: 61 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>Chemotherapy + Placebo | Drug: Placebo<br>* Chemotherapy + Placebo<br>|
| Active Comparator: B<br>Chemotherapy + Sorafenib | Drug: Sorafenib<br>* 2 x 400 mg/d<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Event Free Survival of all AML patients |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Event Free Survival of AML patients with Flt3-ITD mutations |  |  | 
| Median Event Free Survival of the patients in each of the four strata (Flt3 Non-ITD/NPM1 WT, Flt3 Non-ITD/NPM1 mut, Flt3 ITD/NPM1 WT, Flt3 ITD/NPM1 mut) |  |  | 
| Median Overall Survival of AML patients with Flt3-ITD mutations |  |  | 
| Median Overall Survival of all AML patients |  |  | 
| Rate of Complete Remission in all AML patients |  |  | 
| Rate of Molecular Remission in all AML patients |  |  | 
| Toxicity |  |  | 
| Evidence of Minimal Residual Disease in all AML patients |  |  | 
| Development of Biomarkers indicating the course of disease |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib, Acute Myeloid Leukemia, Flt3, AML, Kinase Inhibitor