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

Sponsor

University Hospital Muenster (Other)

Overall Status

Completed

CT.gov ID

NCT00373373

Collaborator

Bayer (Industry)

200

Enrollment

Locations

Arms

Duration (Months)

11.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Sorafenib Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Jul 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: A Chemotherapy + Placebo	Drug: Placebo Chemotherapy + Placebo
Active Comparator: B Chemotherapy + Sorafenib	Drug: Sorafenib 2 x 400 mg/d Other Names: Nexavar

Arm

Intervention/Treatment

Placebo Comparator: A

Chemotherapy + Placebo

Drug: Placebo

Chemotherapy + Placebo

Active Comparator: B

Chemotherapy + Sorafenib

Drug: Sorafenib

2 x 400 mg/d

Other Names:

Nexavar

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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