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

Acute Myeloid Leukemia Clinical Trial

— AML-AZA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00915252
• Other study ID #: 101010
• Status: Completed
• Phase: Phase 2
• First received: June 3, 2009
• Last updated: December 13, 2012
• Start date: July 2009
• Est. completion date: December 2012

Study information

• Verified date: December 2012
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 61 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• 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

Locations

Country	Name	City	State
Germany	RWTH Aachen, Medizinische Klinik IV	Aachen
Germany	Sozialstiftung Bamberg, Klinikum am Bruderwald, Med. Klinik V	Bamberg
Germany	Klinikum Bayreuth, Medizinische Klinik IV	Bayreuth
Germany	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	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	Universitätsklinikum Erlangen, Medizinische Klinik 5	Erlangen
Germany	Universitätsklinikum Essen, Klinik für Hämatologie	Essen
Germany	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)
Germany	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	Stiftungsklinikum Mittelrhein, Hämatologie/ Onkologie	Koblenz
Germany	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	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	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II	Wurzburg

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Muenster	Amgen, Celgene Corporation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Event Free Survival (EFS) of all AML patients		continously up to 12 months after start of study	No
Secondary	Median event free survival of AML patients with different cytogenetic and molecular risk groups		continously up to 12 months after study start	No
Secondary	Median overall survival of all AML patients		continously up to 12 month after start of study	No
Secondary	Median overall survival of AML patients with different cytogenetic and molecular risk groups		continously up to 12 month after start of study	No
Secondary	Relapse free survival		continously up to 12 months after start of study	No