Back to resultsEfficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Sorafenib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Sorafenib, Acute Myeloid Leukemia, Flt3, AML, Kinase Inhibitor
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, 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
Sites / Locations
- Charité Campus Benjamin Franklin, Med. Klinik III
- Klinikum Chemnitz GmbH, Klinik für Innere Medizin III
- Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik I
- St. Johannes Hospital, Medizinische Klinik II
- Universitätsklinikum Essen, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik für Hämatologie
- Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik II
- Allgemeines Krankenhaus St. Georg, Hämatologische Abteilung
- Universitätsklinikum Heidelberg, Med. Klinik V
- Klinikum der Universität zu Köln, Klinik I für Innere Medizin
- Klinikum der Johannes Gutenberg Universität, 3. Medizinische Klinik und Poliklinik
- Philipps Universität, Abteilung für Hämatologie, Onkologie und Immunologie
- Klinik für Hämatologie und Onkologie Klinikum Minden
- TU München, Medizinische Klinik III
- Universitätsklinikum Münster, Medizinische Klinik A
- Klinikum Nürnberg, 5. Medizinische Klinik Einheit für Knochenmarktransplantation
- Universität Regensburg, Abteilung für Hämatologie und Internistische Onkologie
- Robert-Bosch Krankenhaus Stuttgart
- Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
A
B
Arm Description
Chemotherapy + Placebo
Chemotherapy + Sorafenib
Outcomes
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
Full Information
NCT ID
NCT00373373
First Posted
September 6, 2006
Last Updated
August 18, 2009
Sponsor
University Hospital Muenster
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00373373
Brief Title
Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
University Hospital Muenster
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Sorafenib, Acute Myeloid Leukemia, Flt3, AML, Kinase Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Placebo Comparator
Arm Description
Chemotherapy + Placebo
Arm Title
B
Arm Type
Active Comparator
Arm Description
Chemotherapy + Sorafenib
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Nexavar
Intervention Description
2 x 400 mg/d
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Chemotherapy + Placebo
Primary Outcome Measure Information:
Title
Median Event Free Survival of all AML patients
Secondary Outcome Measure Information:
Title
Median Event Free Survival of AML patients with Flt3-ITD mutations
Title
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)
Title
Median Overall Survival of AML patients with Flt3-ITD mutations
Title
Median Overall Survival of all AML patients
Title
Rate of Complete Remission in all AML patients
Title
Rate of Molecular Remission in all AML patients
Title
Toxicity
Title
Evidence of Minimal Residual Disease in all AML patients
Title
Development of Biomarkers indicating the course of disease
10. Eligibility
Sex
All
Minimum Age & Unit of Time
61 Years
Accepts Healthy Volunteers
No
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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hubert Serve, MD
Organizational Affiliation
Klinikum der J.W. Goethe Universität Frankfurt, Med. Klinik II
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité Campus Benjamin Franklin, Med. Klinik III
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Klinikum Chemnitz GmbH, Klinik für Innere Medizin III
City
Chemnitz
ZIP/Postal Code
09113
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik I
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
St. Johannes Hospital, Medizinische Klinik II
City
Duisburg
ZIP/Postal Code
47166
Country
Germany
Facility Name
Universitätsklinikum Essen, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik für Hämatologie
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik II
City
Frankfurt / Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Allgemeines Krankenhaus St. Georg, Hämatologische Abteilung
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitätsklinikum Heidelberg, Med. Klinik V
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany
Facility Name
Klinikum der Universität zu Köln, Klinik I für Innere Medizin
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Klinikum der Johannes Gutenberg Universität, 3. Medizinische Klinik und Poliklinik
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Philipps Universität, Abteilung für Hämatologie, Onkologie und Immunologie
City
Marburg
ZIP/Postal Code
35043
Country
Germany
Facility Name
Klinik für Hämatologie und Onkologie Klinikum Minden
City
Minden
ZIP/Postal Code
32423
Country
Germany
Facility Name
TU München, Medizinische Klinik III
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitätsklinikum Münster, Medizinische Klinik A
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Klinikum Nürnberg, 5. Medizinische Klinik Einheit für Knochenmarktransplantation
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Universität Regensburg, Abteilung für Hämatologie und Internistische Onkologie
City
Regensburg
ZIP/Postal Code
93042
Country
Germany
Facility Name
Robert-Bosch Krankenhaus Stuttgart
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany
Facility Name
Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II
City
Würzburg
ZIP/Postal Code
97979
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Efficacy of Sorafenib Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML
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