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

NCT00915252 | Completed Phase 2 DMC

• 1 other identifier: 101010
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 27

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).

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; azacitidine; elderly; demethylating agent; flt3; AML

Outcome Measures

Primary Outcomes (1)

• Median Event Free Survival (EFS) of all AML patients

  continously up to 12 months after start of study

Secondary Outcomes (4)

• Median event free survival of AML patients with different cytogenetic and molecular risk groups

  continously up to 12 months after study start

• Median overall survival of all AML patients

  continously up to 12 month after start of study

• Median overall survival of AML patients with different cytogenetic and molecular risk groups

  continously up to 12 month after start of study

• Relapse free survival

  continously up to 12 months after start of study

Study Arms (2)

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

standard chemotherapy

ACTIVE COMPARATOR

Patients enrolled in this arm will receive standard chemotherapy treatment.

Drug: standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine

Interventions

azacitidine DRUG

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.

Also known as: 5-azacytidine, Vidaza

5-azacytidine

standard chemotherapy (7+3 scheme): Daunorubicin, Cytarabine DRUG

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

Also known as: Ara-C, Daunoblastin, DaunoXome, Alexan, Ara-cell, Udicil

standard chemotherapy

Eligibility Criteria

• Age: 61 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Muenster: lead
• Celgene Corporation: collaborator
• Amgen: collaborator

Study Sites (27)

RWTH Aachen, Medizinische Klinik IV

Aachen, 52074, Germany

Location

Sozialstiftung Bamberg, Klinikum am Bruderwald, Med. Klinik V

Bamberg, 96049, Germany

Location

Klinikum Bayreuth, Medizinische Klinik IV

Bayreuth, 95445, Germany

Location

Charite Campus Benjamin Franklin, Universitätsmedizin Berlin, Medizinische Klinik III

Berlin, Germany

Location

Städt. Kliniken Bielefeld gem. GmbH, Klinikum Mitte, Klinik für Hämatologie, Onkologie, Palliativmedizin

Bielefeld, 33604, Germany

Location

Klinikum Chemnitz, Krankenhaus Küchenwald, Klinik für Innere Medizin III

Chemnitz, Germany

Location

Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I

Dresden, Germany

Location

Katholische Krankenhaus Duisburg

Duisburg, 47166, Germany

Location

Universitätsklinikum Erlangen, Medizinische Klinik 5

Erlangen, Germany

Location

Universitätsklinikum Essen, Klinik für Hämatologie

Essen, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), 15236, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität Frakfurt am Main

Frankfurt am Main, Germany

Location

Asklepios Klinik St. Georg, Hämatologische Abteilung

Hamburg, Germany

Location

St. Bernward Krankenhaus Hildesheim, Medizinische Klinik II

Hildesheim, Germany

Location

Westpfalz-Klinikum GmbH, Med. Klinik I

Kaiserslautern, 67655, Germany

Location

Stiftungsklinikum Mittelrhein, Hämatologie/ Onkologie

Koblenz, 56068, Germany

Location

Johannes Gutenberg-Universität Mainz Klinikum, III. Medizinische Klinik und Poliklinik

Mainz, Germany

Location

Phillips Universität Marburg, Fachbereich 20, ZIM

Marburg, Germany

Location

Klinikum rechts der Isar, III. Medizinische Klinik

München, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A

Münster, 48149, Germany

Location

Klinikum Nürnberg, Medizinische Klinik 5

Nuremberg, Germany

Location

Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie

Osnabrück, Germany

Location

Klinikum der Universität Regensburg, Klinik und Poliklinik für Innere Medizin I

Regensburg, Germany

Location

Robert-Bosch-Krankenhaus, Zentrum für Innere Medizin

Stuttgart, Germany

Location

Klinikum Mutterhaus der Borromäerinnen, Innere Medizin I

Trier, 2920, Germany

Location

Dr. Horst-Schmidt-Kliniken

Wiesbaden, 65199, Germany

Location

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II

Würzburg, Germany

Location

Related Publications (1)

• 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.

  PMID: 23300745 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Carsten Müller-Tidow, MD

  Universitätsklinikum Münster, Medizinische Klinik A

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 17, 2012

Record last verified: 2012-12

Locations

DE (27)