Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML - Full Text View

Sponsor:	University Hospital Muenster
Collaborator:	Bayer
Information provided by:	University Hospital Muenster
ClinicalTrials.gov Identifier:	NCT00373373

Purpose

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).

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Sorafenib Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:

Median Event Free Survival of all AML patients

Secondary Outcome Measures:

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

Estimated Enrollment:	200
Study Start Date:	September 2006
Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: A Chemotherapy + Placebo	Drug: Placebo Chemotherapy + Placebo
Active Comparator: B Chemotherapy + Sorafenib	Drug: Sorafenib 2 x 400 mg/d Other Name: Nexavar

Eligibility

Ages Eligible for Study:	61 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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, 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373373

Locations

Germany
Charité Campus Benjamin Franklin, Med. Klinik III
Berlin, Germany, 12203
Klinikum Chemnitz GmbH, Klinik für Innere Medizin III
Chemnitz, Germany, 09113
Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik I
Dresden, Germany, 01307
St. Johannes Hospital, Medizinische Klinik II
Duisburg, Germany, 47166
Universitätsklinikum Essen, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik für Hämatologie
Essen, Germany, 45147
Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik II
Frankfurt / Main, Germany, 60590
Allgemeines Krankenhaus St. Georg, Hämatologische Abteilung
Hamburg, Germany, 20099
Universitätsklinikum Heidelberg, Med. Klinik V
Heidelberg, Germany, D-69120
Klinikum der Universität zu Köln, Klinik I für Innere Medizin
Köln, Germany, 50937
Klinikum der Johannes Gutenberg Universität, 3. Medizinische Klinik und Poliklinik
Mainz, Germany, 55101
Philipps Universität, Abteilung für Hämatologie, Onkologie und Immunologie
Marburg, Germany, 35043
Klinik für Hämatologie und Onkologie Klinikum Minden
Minden, Germany, 32423
TU München, Medizinische Klinik III
München, Germany, 81675
Universitätsklinikum Münster, Medizinische Klinik A
Münster, Germany, 48149
Klinikum Nürnberg, 5. Medizinische Klinik Einheit für Knochenmarktransplantation
Nürnberg, Germany, 90419
Universität Regensburg, Abteilung für Hämatologie und Internistische Onkologie
Regensburg, Germany, 93042
Robert-Bosch Krankenhaus Stuttgart
Stuttgart, Germany, 70376
Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II
Würzburg, Germany, 97979

Sponsors and Collaborators

University Hospital Muenster

Bayer

Investigators

Principal Investigator:

Hubert Serve, MD

Klinikum der J.W. Goethe Universität Frankfurt, Med. Klinik II

More Information

No publications provided

Responsible Party:	Hubert Serve (Principal Investigator), Klinikum der J.W. Goethe Universität Frankfurt, Med. Klinik II
ClinicalTrials.gov Identifier:	NCT00373373 History of Changes
Other Study ID Numbers:	KKS/INNERE_A/AML2006, EudraCT Number: 2005-005966-35, Sorafenib in AML
Study First Received:	September 6, 2006
Last Updated:	August 18, 2009
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:

Sorafenib
Acute Myeloid Leukemia
Flt3
AML
Kinase Inhibitor

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Sorafenib

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 13, 2012