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

December 13, 2012 updated by: University Hospital Muenster

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
214

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

61 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • Vidaza
  • 5-azacytidine
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:
  • Alexan
  • Ara-C
  • Udicil
  • Daunoblastin
  • DaunoXome
  • Ara-cell

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Median Event Free Survival (EFS) of all AML patients
Time Frame: continously up to 12 months after start of study
continously up to 12 months after start of study

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Median event free survival of AML patients with different cytogenetic and molecular risk groups
Time Frame: continously up to 12 months after study start
continously up to 12 months after study start
Median overall survival of all AML patients
Time Frame: continously up to 12 month after start of study
continously up to 12 month after start of study
Median overall survival of AML patients with different cytogenetic and molecular risk groups
Time Frame: continously up to 12 month after start of study
continously up to 12 month after start of study
Relapse free survival
Time Frame: continously up to 12 months after start of study
continously up to 12 months after start of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Muenster

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celgene Corporation
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carsten Müller-Tidow, MD, Universitätsklinikum Münster, Medizinische Klinik A

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 3, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 17, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 101010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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