Efficacy of 5-azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) (AML-AZA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00915252
Recruitment Status : Completed
First Posted : June 5, 2009
Last Update Posted : December 17, 2012
Celgene Corporation
Information provided by (Responsible Party):
University Hospital Muenster

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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: azacitidine Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 214 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2009
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: 5-azacytidine
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy preceded by 5-azacytidine. These patients will additionally receive maintenance therapy with 5-azacytidine for one year after start of induction therapy.
Drug: azacitidine

Starting dose has been determined during run-in dose finding part of the study. Starting dose of the interventional drug is 75 mg/m²/d. Application form:

During induction therapy phase: i.v. on days -5--1 before standard chemotherapy for 1 or 2 cycles, During consolidation therapy: s.c. on days -5--1 before standard chemotherapy (2 cycles).

During maintenance therapy: s.c. on days 1-5 on a 28day cycle till maximum one year after start of first induction therapy.

Other Names:
  • 5-azacytidine
  • Vidaza

Active Comparator: standard chemotherapy
Patients enrolled in this arm will receive standard chemotherapy treatment.
Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine

Induction therapy:

Daunorubicin 60mg/m²/d i.v.on days 3,4,5 AraC 100mg/m²/d i.v. on days 1-7

Consolidation therapy:

AraC 1g/m² twice a day on day 1,3,5

Other Names:
  • Ara-C
  • Daunoblastin
  • DaunoXome
  • Alexan
  • Ara-cell
  • Udicil

Primary Outcome Measures :
  1. Median Event Free Survival (EFS) of all AML patients [ Time Frame: continously up to 12 months after start of study ]

Secondary Outcome Measures :
  1. Median event free survival of AML patients with different cytogenetic and molecular risk groups [ Time Frame: continously up to 12 months after study start ]
  2. Median overall survival of all AML patients [ Time Frame: continously up to 12 month after start of study ]
  3. Median overall survival of AML patients with different cytogenetic and molecular risk groups [ Time Frame: continously up to 12 month after start of study ]
  4. Relapse free survival [ Time Frame: continously up to 12 months after start of study ]

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Ages Eligible for Study:   61 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00915252

RWTH Aachen, Medizinische Klinik IV
Aachen, Germany, 52074
Sozialstiftung Bamberg, Klinikum am Bruderwald, Med. Klinik V
Bamberg, Germany, 96049
Klinikum Bayreuth, Medizinische Klinik IV
Bayreuth, Germany, 95445
Charite Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik III
Berlin, Germany
Städt. Kliniken Bielefeld gem. GmbH, Klinikum Mitte, Klinik für Hämatologie, Onkologie, Palliativmedizin
Bielefeld, Germany, 33604
Klinikum Chemnitz, Krankenhaus Küchenwald, Klinik für Innere Medizin III
Chemnitz, Germany
Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I
Dresden, Germany
Katholische Krankenhaus Duisburg
Duisburg, Germany, 47166
Universitätsklinikum Erlangen, Medizinische Klinik 5
Erlangen, Germany
Universitätsklinikum Essen, Klinik für Hämatologie
Essen, Germany
Klinikum Frankfurt (Oder) GmbH
Frankfurt (Oder), Germany, 15236
Klinikum der Johann Wolfgang Goethe-Universität Frakfurt am Main
Frankfurt am Main, Germany
Asklepios Klinik St. Georg, Hämatologische Abteilung
Hamburg, Germany
St. Bernward Krankenhaus Hildesheim, Medizinische Klinik II
Hildesheim, Germany
Westpfalz-Klinikum GmbH, Med. Klinik I
Kaiserslautern, Germany, 67655
Stiftungsklinikum Mittelrhein, Hämatologie/ Onkologie
Koblenz, Germany, 56068
Johannes Gutenberg-Universität Mainz Klinikum, III. Medizinische Klinik und Poliklinik
Mainz, Germany
Phillips Universität Marburg, Fachbereich 20, ZIM
Marburg, Germany
Klinikum rechts der Isar, III. Medizinische Klinik
Muenchen, Germany
Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A
Münster, Germany, 48149
Klinikum Nürnberg, Medizinische Klinik 5
Nurnberg, Germany
Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie
Osnabruck, Germany
Klinikum der Universität Regensburg, Klinik und Poliklinik für Innere Medizin I
Regensburg, Germany
Robert-Bosch-Krankenhaus, Zentrum für Innere Medizin
Stuttgart, Germany
Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I
Trier, Germany, 2920
Dr. Horst-Schmidt-Kliniken
Wiesbaden, Germany, 65199
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II
Wurzburg, Germany
Sponsors and Collaborators
University Hospital Muenster
Celgene Corporation
Principal Investigator: Carsten Müller-Tidow, MD Universitätsklinikum Münster, Medizinische Klinik A

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University Hospital Muenster Identifier: NCT00915252     History of Changes
Other Study ID Numbers: 101010
First Posted: June 5, 2009    Key Record Dates
Last Update Posted: December 17, 2012
Last Verified: December 2012

Keywords provided by University Hospital Muenster:
Acute Myeloid Leukemia
demethylating agent

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors