Clinical trial NCT00373373: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Sorafenib
Acute Myeloid Leukemia
Flt3
AML
Kinase Inhibitor
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2006-09-08
Enrollment: 200
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Median Event Free Survival of all AML patients
Secondary outcomes:
measure: Median Event Free Survival of AML patients with Flt3-ITD mutations
measure: 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)
measure: Median Overall Survival of AML patients with Flt3-ITD mutations
measure: Median Overall Survival of all AML patients
measure: Rate of Complete Remission in all AML patients
measure: Rate of Molecular Remission in all AML patients
measure: Toxicity
measure: Evidence of Minimal Residual Disease in all AML patients
measure: Development of Biomarkers indicating the course of disease
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin, Med. Klinik III
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz GmbH, Klinik für Innere Medizin III
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik I
city: Duisburg
country: Germany
facility: St. Johannes Hospital, Medizinische Klinik II
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik für Hämatologie
city: Frankfurt / Main
country: Germany
facility: Klinikum der J. W. Goethe-Universität Frankfurt am Main, Medizinische Klinik II
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus St. Georg, Hämatologische Abteilung
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Med. Klinik V
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln, Klinik I für Innere Medizin
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Universität, 3. Medizinische Klinik und Poliklinik
city: Marburg
country: Germany
facility: Philipps Universität, Abteilung für Hämatologie, Onkologie und Immunologie
city: Minden
country: Germany
facility: Klinik für Hämatologie und Onkologie Klinikum Minden
city: München
country: Germany
facility: TU München, Medizinische Klinik III
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik A
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg, 5. Medizinische Klinik Einheit für Knochenmarktransplantation
city: Regensburg
country: Germany
facility: Universität Regensburg, Abteilung für Hämatologie und Internistische Onkologie
city: Stuttgart
country: Germany
facility: Robert-Bosch Krankenhaus Stuttgart
city: Würzburg
country: Germany
facility: Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II
Study officials:
affiliation: Klinikum der J.W. Goethe Universität Frankfurt, Med. Klinik II
name: Hubert Serve, MD
role: PRINCIPAL_INVESTIGATOR
References: