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

Study Overview
=================
Brief Summary
-----------------
Sorafenib is a multikinase inhibitor which is acting on various cellular pathways involved in the genesis of acute myeloid leukemia (AML). Sorafenib is therefore a promising candidate for improvement of chemotherapy results in AML. This clinical trial evaluates the efficacy of sorafenib added to standard chemotherapy for AML in patients between 18 and 60 years of age. Patients are randomised to receive either sorafenib capsules or placebo in addition to their chemotherapy. The placebo and the sorafenib group will be compared regarding event-free survival and other clinical outcomes. An event is either treatment failure or relapse or death. According to the study hypothesis, the sorafenib group will have less events than the placebo group.

Official Title
-----------------
A Double-blind, Placebo-controlled, Randomized, Multicenter Phase-II Trial to Assess the Efficacy of Sorafenib Added to Standard Primary Therapy in Patients With Newly Diagnosed AML ≤60 Years of Age

Conditions
-----------------
Acute Myeloid Leukemia (AML)

Intervention / Treatment
-----------------
* Drug: sorafenib
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 or differential blood count must contain ≥ 20% blasts. In AML FAB M6 ≥ 30% of nonerythroid cells in the bone marrow must be leukemic blasts. In AML defined by cytogenetic aberrations, the proportion of blasts may be < 20%. Age ≥ 18 and ≤ 60 years Informed consent, personally signed and dated to participate in the study ECOG performance status of 0-1 Life expectancy of at least 12 weeks Adequate liver and renal function as assessed by laboratory requirements to be conducted within 7 days prior to Screening Exclusion criteria: Patients who are not eligible for standard chemotherapy as per discretion of the treating physician Central nervous system manifestation of AML Cardiac disease: heart failure NYHA III or IV; unstable 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 (creatinine clearance < 30 ml/min) (Cockcroft-Gault formula) Patients undergoing renal dialysis Chronic pulmonary disease with relevant hypoxia Known HIV and/or hepatitis C infection Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders 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 jeopardize compliance of the protocol Patients with major surgery, open biopsy or significant traumatic injury within 4 weeks of start of first dose Serious, non-healing wound, ulcer or bone fracture Uncontrolled active infection > Grade 2 NCI-CTC version 3.0 Concurrent malignancies other than AML History of organ allograft Allergy to study medication or excipients in study medication

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib<br>Induction, Consolidation and Maintenance plus Sorafenib 2x 400 mg/d | Drug: sorafenib<br>* Standard AML chemotherapy plus sorafenib 400 mg BID<br>* Other names: nexavar;|
| Placebo Comparator: Placebo<br>Induction, Consolidation and Maintenance plus Placebo | Drug: placebo<br>* Standard AML chemotherapy plus placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 36 months | 
| Rate of complete remissions |  | 12 weeks | 
| Toxicity |  | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AML, sorafenib