Clinical trial NCT00915252: Efficacy of 5-azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Official title: A Randomized, Multi-center Phase II Trial to Assess the Efficacy of 5-azacytidine 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: Acute Myeloid Leukemia
azacitidine
elderly
demethylating agent
flt3
AML
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Amgen
First posted: 2009-06-05
Enrollment: 214
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 5-azacytidine 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 or WHO classification, including AML evolving from MDS or other hematological diseases and AML after previous cytotoxic therapy or radiation (secondary AML).
* Bone marrow aspirate or biopsy must contain ≥ 20% blasts of all nucleated cells or differential blood count must contain ≥ 20% blasts. In AML FAB M6 ≥ 30% of non-erythroid cells in the bone marrow must be leukemic blasts. In AML defined by cytogenetic aberrations the proportion of blasts may be \< 20%.
* 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 5-azacytidine treatment and for at least 3 months after the last administration of 5-azacytidine.

Exclusion Criteria:

* Patients who are not eligible for standard chemotherapy as described in chapter 5.2 and 5.3
* Hyperleukocytosis (leukocytes \> 20,000/µl) at study entry. These patients should be treated with hydroxyurea or receive leukocytapheresis treatment (if leukocytes \> 100,000/µl) according to routine practice and entered into the study when leukocyte counts below 20,000/µl are reached. This applies only for the controlled part of the study.
* Patients with initial hyperleukocytosis above 20,000/µl can only be enrolled into the controlled part of the study, but not in the run-in dose finding part.
* Known central nervous system manifestation of AML
* Cardiac Disease: Heart failure NYHA class 3 or 4; unstable 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)
* Inadequate liver function (ALT and AST ≥ 2.5 x ULN) if not caused by leukemic infiltration
* Total bilirubin ≥ 1.5 x ULN if not caused by leukemic infiltration
* Known HIV and/or hepatitis C infection
* Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
* Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders
* Uncontrolled active infection
* Concurrent malignancies other than AML with an estimated life expectancy of less than two years
* History of organ allograft
* Hypersensitivity to cytarabine (not including drug fever or exanthema), daunorubicin, azacytidine or mannitol
* Previous treatment of AML except hydroxyurea and up to 2 days of ≤100 mg/m2/d cytarabine
* Previous therapy with 5-azacytidine (i.e. for an antecedent myelodysplastic syndrome)
* Patients with investigational drug therapy outside of this trial during or within 4 weeks of study entry should be discussed with the study office whether study participation is possible
* Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol

Primary outcomes:
measure: Median Event Free Survival (EFS) of all AML patients
timeFrame: continously up to 12 months after start of study
Secondary outcomes:
measure: Median event free survival of AML patients with different cytogenetic and molecular risk groups
timeFrame: continously up to 12 months after study start
measure: Median overall survival of all AML patients
timeFrame: continously up to 12 month after start of study
measure: Median overall survival of AML patients with different cytogenetic and molecular risk groups
timeFrame: continously up to 12 month after start of study
measure: Relapse free survival
timeFrame: continously up to 12 months after start of study
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen, Medizinische Klinik IV
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg, Klinikum am Bruderwald, Med. Klinik V
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth, Medizinische Klinik IV
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik III
city: Bielefeld
country: Germany
facility: Städt. Kliniken Bielefeld gem. GmbH, Klinikum Mitte, Klinik für Hämatologie, Onkologie, Palliativmedizin
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz, Krankenhaus Küchenwald, Klinik für Innere Medizin III
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I
city: Duisburg
country: Germany
facility: Katholische Krankenhaus Duisburg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Medizinische Klinik 5
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hämatologie
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Frakfurt am Main
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg, Hämatologische Abteilung
city: Hildesheim
country: Germany
facility: St. Bernward Krankenhaus Hildesheim, Medizinische Klinik II
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH, Med. Klinik I
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein, Hämatologie/ Onkologie
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität Mainz Klinikum, III. Medizinische Klinik und Poliklinik
city: Marburg
country: Germany
facility: Phillips Universität Marburg, Fachbereich 20, ZIM
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar, III. Medizinische Klinik
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A
city: Nurnberg
country: Germany
facility: Klinikum Nürnberg, Medizinische Klinik 5
city: Osnabruck
country: Germany
facility: Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg, Klinik und Poliklinik für Innere Medizin I
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus, Zentrum für Innere Medizin
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Wurzburg
country: Germany
facility: Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II
Study officials:
affiliation: Universitätsklinikum Münster, Medizinische Klinik A
name: Carsten Müller-Tidow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krug U, Koschmieder A, Schwammbach D, Gerss J, Tidow N, Steffen B, Bug G, Brandts CH, Schaich M, Rollig C, Thiede C, Noppeney R, Stelljes M, Buchner T, Koschmieder S, Duhrsen U, Serve H, Ehninger G, Berdel WE, Muller-Tidow C. Feasibility of azacitidine added to standard chemotherapy in older patients with acute myeloid leukemia--a randomised SAL pilot study. PLoS One. 2012;7(12):e52695. doi: 10.1371/journal.pone.0052695. Epub 2012 Dec 31.