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

NCT ID: NCT00915252

Last Updated: 2012-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2012-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: 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.

standard chemotherapy

Patients enrolled in this arm will receive standard chemotherapy treatment.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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

Interventions

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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

5-azacytidine; Vidaza; Ara-C; Daunoblastin; DaunoXome; Alexan; Ara-cell; Udicil

Eligibility 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

• Minimum Eligible Age: 61 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carsten Müller-Tidow, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Münster, Medizinische Klinik A

Locations

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

München, , Germany

Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A

Münster, , Germany

Klinikum Nürnberg, Medizinische Klinik 5

Nuremberg, , Germany

Klinikum Osnabrück, Klinik für Onkologie, Hämatologie, Immunologie

Osnabrück, , 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

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 23300745 (View on PubMed)

Other Identifiers

101010

Identifier Type: -

Identifier Source: org_study_id