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

Phase 2
Completed
Conditions
Acute Myeloid Leukemia
Interventions
Drug: Placebo
Registration Number
NCT00373373
Lead Sponsor
University Hospital Muenster
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
APlaceboChemotherapy + Placebo
BSorafenibChemotherapy + Sorafenib
Primary Outcome Measures
NameTimeMethod
Median Event Free Survival of all AML patients
Secondary Outcome Measures
NameTimeMethod
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
Toxicity
Rate of Molecular Remission in all AML patients
Evidence of Minimal Residual Disease in all AML patients
Development of Biomarkers indicating the course of disease

Trial Locations

Locations (18)

Klinikum der Universität zu Köln, Klinik I für Innere Medizin

🇩🇪

Köln, Germany

Universitätsklinikum Münster, Medizinische Klinik A

🇩🇪

Münster, Germany

Robert-Bosch Krankenhaus Stuttgart

🇩🇪

Stuttgart, Germany

Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik I

🇩🇪

Dresden, Germany

Charité Campus Benjamin Franklin, Med. Klinik III

🇩🇪

Berlin, Germany

Klinikum Chemnitz GmbH, Klinik für Innere Medizin III

🇩🇪

Chemnitz, Germany

Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik II

🇩🇪

Frankfurt / Main, Germany

Universitätsklinikum Essen, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik für Hämatologie

🇩🇪

Essen, Germany

Universitätsklinikum Heidelberg, Med. Klinik V

🇩🇪

Heidelberg, Germany

Philipps Universität, Abteilung für Hämatologie, Onkologie und Immunologie

🇩🇪

Marburg, Germany

Allgemeines Krankenhaus St. Georg, Hämatologische Abteilung

🇩🇪

Hamburg, Germany

Klinikum der Johannes Gutenberg Universität, 3. Medizinische Klinik und Poliklinik

🇩🇪

Mainz, Germany

Klinik für Hämatologie und Onkologie Klinikum Minden

🇩🇪

Minden, Germany

TU München, Medizinische Klinik III

🇩🇪

München, Germany

Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II

🇩🇪

Würzburg, Germany

St. Johannes Hospital, Medizinische Klinik II

🇩🇪

Duisburg, Germany

Klinikum Nürnberg, 5. Medizinische Klinik Einheit für Knochenmarktransplantation

🇩🇪

Nürnberg, Germany

Universität Regensburg, Abteilung für Hämatologie und Internistische Onkologie

🇩🇪

Regensburg, Germany

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