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Efficacy of 5-Azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) (AML-AZA)
This study is not yet open for participant recruitment.
Verified by University Hospital Muenster, June 2009
First Received: June 3, 2009   Last Updated: June 4, 2009   History of Changes
Sponsors and Collaborators: University Hospital Muenster
Celgene Corporation
Amgen
Information provided by: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT00915252
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Drug: azacitidine
Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Randomized, Multi-Center Phase II Trail to Assess the Efficacy of 5-Azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • Median Event Free Survival (EFS) of all AML patients [ Time Frame: continously up to 12 months after start of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median event free survival of AML patients with different cytogenetic and molecular risk groups [ Time Frame: continously up to 12 months after study start ] [ Designated as safety issue: No ]
  • Median overall survival of all AML patients [ Time Frame: continously up to 12 month after start of study ] [ Designated as safety issue: No ]
  • Median overall survival of AML patients with different cytogenetic and molecular risk groups [ Time Frame: continously up to 12 month after start of study ] [ Designated as safety issue: No ]
  • Relapse free survival [ Time Frame: continously up to 12 months after start of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 216
Study Start Date: July 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
5-azacytidine: Experimental
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 to be determined during run-in dose finding part of the study. Starting dose of the interventional drug will be most likely either 75 or 37,5mg/m²/d resp. 18mg/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.

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

Induction therapy:

Daunorubicin 45mg/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


  Eligibility

Ages Eligible for Study:   61 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00915252

Contacts
Contact: Carsten Müller-Tidow, MD +49 (0)251 83-52995 muellerc@uni-muenster.de

Locations
Germany
Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A
48149 Münster, Germany
Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I
01307 Dresden, Germany
Klinikum der Johann Wolfgang Goethe-Universität Frakfurt am Main
60590 Frankfurt, Germany
Universitätsklinikum Erlangen, Medizinische Klinik 5
91054 Erlangen, Germany
St. Bernward Krankenhaus Hildesheim, Medizinische Klinik II
31134 Hildesheim, Germany
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II
97070 Würzburg, Germany
Universitätsklinikum Essen, Klinik für Hämatologie
45122 Essen, Germany
Johannes Gutenberg-Universität Mainz Klinikum, III. Medizinische Klinik und Poliklinik
55101 Mainz, Germany
Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie
49076 Osnabrück, Germany
Asklepios Klinik St. Georg, Hämatologische Abteilung
20099 Hamburg, Germany
Klinikum rechts der Isar, III. Medizinische Klinik
81675 München, Germany
Klinikum der Universität Regensburg, Klinik und Poliklinik für Innere Medizin I
93042 Regensburg, Germany
Robert-Bosch-Krankenhaus, Zentrum für Innere Medizin
70376 Stuttgart, Germany
Phillips Universität Marburg, Fachbereich 20, ZIM
35032 Marburg, Germany
Klinikum Nürnberg, Medizinische Klinik 5
90340 Nürnberg, Germany
Klinikum Chemnitz, Krankenhaus Küchenwald, Klinik für Innere Medizin III
09113 Chemnitz, Germany
Charite Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik III
12203 Berlin, Germany
Sponsors and Collaborators
University Hospital Muenster
Celgene Corporation
Amgen
Investigators
Principal Investigator: Carsten Müller-Tidow, MD Universitätsklinikum Münster, Medizinische Klinik A
  More Information

No publications provided

Responsible Party: University Hospital Muenster, Medizinische Klinik und Poliklinik A ( Prof. Dr. med. Carsten Müller-Tidow )
Study ID Numbers: 101010
Study First Received: June 3, 2009
Last Updated: June 4, 2009
ClinicalTrials.gov Identifier: NCT00915252     History of Changes
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:
Acute Myeloid Leukemia
azacitidine
elderly
demethylating agent
flt3
AML

Study placed in the following topic categories:
Antimetabolites
Anti-Bacterial Agents
Daunorubicin
Leukemia
Acute Myelocytic Leukemia
Azacitidine
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine

Additional relevant MeSH terms:
Antimetabolites
Daunorubicin
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Leukemia, Myeloid
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Pharmacologic Actions
Leukemia
Neoplasms
Therapeutic Uses
Azacitidine

ClinicalTrials.gov processed this record on September 03, 2009