A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care

NCT ID: NCT00071799

Last Updated: 2019-10-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-11-01

Study Completion Date

2007-07-01

Brief Summary

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The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled.

See study AZA PH GL 2003 CL 001 E for information about the extension to this study.

Detailed Description

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Comparison/Control Interventions offered the physician three options:

* Best supportive care (BSC) alone,
* Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or
* Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle).

All three options included best supportive care. Neither the experimental group (azacitidine) nor any of the comparison/control options allowed use of erythropoietin.

Duration of Intervention: Patients will be treated until death, withdrawal, unacceptable toxicity or conclusion of the study.

Conditions

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Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Azacitidine

Study Drug plus best supportive care. Treatment with erythropoietin was not permitted

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m\^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.

Conventional Care

Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted

Group Type ACTIVE_COMPARATOR

Physician Choice

Intervention Type OTHER

Physician Choice was one of three options:

* Best supportive care (BSC) alone,
* Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or
* Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle).

All three options included best supportive care

Interventions

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Azacitidine

Azacitidine was injected subcutaneously (SC) at an initial dose of 75mg/m\^2/day for 7 days. The 7-day dosing was repeated every 28 days with dose adjustment based on predefined hematology and renal laboratory results. Number of cycles: Azacitidine treatment was to be continued until the end of the study unless treatment was discontinued due to unacceptable toxicity, relapse after complete or partial response, transformation to AML or disease progression.

Intervention Type DRUG

Physician Choice

Physician Choice was one of three options:

* Best supportive care (BSC) alone,
* Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or
* Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle).

All three options included best supportive care

Intervention Type OTHER

Other Intervention Names

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AZA cytarabine anthracycline

Eligibility Criteria

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Inclusion Criteria

* Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High.
* Be 18 years of age or older
* Have a life expectancy of at least 3 months
* Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
* Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
* Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
* Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal

Exclusion Criteria

* Secondary myelodysplastic syndromes (MDS)
* Prior treatment with azacitidine;
* Prior history of acute myeloid leukemia (AML);
* Malignant disease diagnosed within prior 12 months;
* Metastatic disease;
* Hepatic tumors;
* Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
* Prior transplantation or cytotoxic therapy to treat MDS;
* Serious medical illness likely to limit survival to 12 months or less;
* Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
* Active HIV, viral hepatitis type B or C;
* Treatment with investigational drugs during prior 30 days;
* Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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CL Beach

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

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University of Alabama School of Medicine

Birmingham, Alabama, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Oregon Cancer Center

Portland, Oregon, United States

Site Status

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

The Newcastle Mater Miseriecordiae Hospital

Warratah, New South Wales, Australia

Site Status

Royal Brisbane Hospital

Hersten, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Peter MacCallum Cancer Institute

East Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

The Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

First Clinical Base - Clinic of Hematology, MHAT - Pleven

Pleven, , Bulgaria

Site Status

MHAT "St George" Clinic of Hematology, Plovdiv

Plovdiv, , Bulgaria

Site Status

III-rd Internal Department, District Dispensary for Oncology diseases with stationary(DDOncDIU)

Plovdiv, , Bulgaria

Site Status

National Centre of Hematology and Transfusiology, Sofia

Sofia, , Bulgaria

Site Status

Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of Hematology

Varna, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment "Sveta Marina"

Varna, , Bulgaria

Site Status

Fakultni nemocnice Brno

Jihlavska, Brno, Czechia

Site Status

Fakultni nemocnice Hradec Kralove

Sokolska, Hradec Kralove, Czechia

Site Status

Fakultni Nemocnice Olomouc

Olomouc, , Czechia

Site Status

Vseobecna Fakultni Nemocnice

Prague, , Czechia

Site Status

Uslav Hematologie a Krevni Transfuze

Prague, , Czechia

Site Status

Chu D'Angers

Angers, , France

Site Status

Hopital Beaujon

Clichy, , France

Site Status

Che De Lille

Lille, , France

Site Status

Hospital Edouard Herriot

Lyon, , France

Site Status

Institute Paoli Calmettes

Marseille, , France

Site Status

Chu De Nantes

Nantes, , France

Site Status

Hospital Saint Louis

Paris, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Chu Purpan

Toulouse, , France

Site Status

Universitatsklinikum Benjamin Franklin

Hindenburgdamm, State of Berlin, Germany

Site Status

Universitatsklinikum Bonn

Bonn, , Germany

Site Status

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Site Status

Universitatsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status

St Johannes Hospital

Duisburg, , Germany

Site Status

Heinrich-Heine University Dusseldorf

Düsseldorf, , Germany

Site Status

University Essen

Essen, , Germany

Site Status

Gerorg-August-Universitat Gottingen

Göttingen, , Germany

Site Status

Allgemeines Krankenhaus St. Georg

Hamburg, , Germany

Site Status

Universitatsklinikum Hambur-Eppendorf

Hamburg, , Germany

Site Status

Universitatsklinikum Kiel II

Kiel, , Germany

Site Status

Universitatsklinikum Ulm

Ulm, , Germany

Site Status

University Hospital-Attikon

Haidari, Athens, Greece

Site Status

University General Hospital of Heraklio Voutes

Heraklio, Crete, Greece

Site Status

District General Hospital of Athens

Athens, , Greece

Site Status

General Hospital of Chest Disease

Athens, , Greece

Site Status

University General Hospital of Ioannina

Ioannina, , Greece

Site Status

University General Hospital of Patra Rio

Pátrai, , Greece

Site Status

Orszagos Gyogyintezeti Kozpont

Budapest, , Hungary

Site Status

University of Pecs, 1st Dept of Internal Medicine

Pécs, , Hungary

Site Status

University of Szeged, 2nd Department of Internal Medicine

Szeged, , Hungary

Site Status

Policlinico S. Orsola-Malpighi

Bologna, , Italy

Site Status

Universita di Firenze

Florence, , Italy

Site Status

Ospedale San Martino

Genova, , Italy

Site Status

Instituto Nazionale Dei Tumori

Milan, , Italy

Site Status

Centro Oncologico Modenese

Modena, , Italy

Site Status

Ospedale San Eugenio

Roma, , Italy

Site Status

Policlinico Gemelli

Roma, , Italy

Site Status

Instituto Nazionale Tumori "Regina Elena"

Roma, , Italy

Site Status

Ospedale Casa Sollievo Della Sofferenza - Irrc

San Giovanni Rotondo, , Italy

Site Status

Universita Degli Studi Di Sassari

Sassari, , Italy

Site Status

VU University Medical Center Amsterdam

Amsterdam, , Netherlands

Site Status

Univ Hospital St. Radboud

Nijmejen, , Netherlands

Site Status

Samodzielny Publiczny Szpital Kliniczny Nr 1

Gdansk, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny

Lodz, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny

Lublin, , Poland

Site Status

Wojskowy Instytut Medyczny

Warsaw, , Poland

Site Status

Samodzelny Publiczny Centralny Szpital Kliniczny

Warsaw, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny Nr 1

Wroclaw, , Poland

Site Status

Burdenko Central Military Clinical Hospital

Moscow, , Russia

Site Status

Blokhin Cancer Research Center

Moscow, , Russia

Site Status

Scientific Haematology Center, Moscow

Moscow, , Russia

Site Status

Institute of Haematology & Blood Transfusion

Saint Petersburg, , Russia

Site Status

Pavlov State Medical University

Saint Petersburg, , Russia

Site Status

Pavlov State Medical University

Saint Petersburg, , Russia

Site Status

City Hospital #31

Saint Petersburg, , Russia

Site Status

Hospital Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Hospital Clinic

Barcelona, , Spain

Site Status

Hospital Universitario Germans Trias I Pujol

Barcelona, , Spain

Site Status

Hospital de Leon

León, , Spain

Site Status

Hospital Universitario De La Princesa

Madrid, , Spain

Site Status

Hospital Ramon Y Cajal

Madrid, , Spain

Site Status

Hospital La Paz, Madrid

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Son Llatzer

Palma de Mallorca, , Spain

Site Status

Hospital Universitario Del Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Lund Universtiy Hospital

Lund, , Sweden

Site Status

University Hospital MAS

Malmo, , Sweden

Site Status

Huddinge University Hospital

Stockholm, , Sweden

Site Status

Uppsala University Hospital

Uppsala, , Sweden

Site Status

Royal Bournemouth General Hospital

Bournemouth, , United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

Kings College Hospital NHS Trust

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Countries

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United States Australia Bulgaria Czechia France Germany Greece Hungary Italy Netherlands Poland Russia Spain Sweden United Kingdom

References

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Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.

Reference Type RESULT
PMID: 20026804 (View on PubMed)

Fenaux P, Gattermann N, Seymour JF, Hellstrom-Lindberg E, Mufti GJ, Duehrsen U, Gore SD, Ramos F, Beyne-Rauzy O, List A, McKenzie D, Backstrom J, Beach CL. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol. 2010 Apr;149(2):244-9. doi: 10.1111/j.1365-2141.2010.08082.x. Epub 2010 Feb 5.

Reference Type RESULT
PMID: 20136825 (View on PubMed)

Santini V, Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Silverman LR, List A, Gore SD, Seymour JF, Backstrom J, Beach CL. Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. Eur J Haematol. 2010 Aug;85(2):130-8. doi: 10.1111/j.1600-0609.2010.01456.x. Epub 2010 Apr 12.

Reference Type RESULT
PMID: 20394651 (View on PubMed)

Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellstrom-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, McKenzie D, Beach CL. Effects of azacitidine compared with conventional care regimens in elderly (>/= 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol. 2010 Dec;76(3):218-27. doi: 10.1016/j.critrevonc.2010.04.005. Epub 2010 May 6.

Reference Type RESULT
PMID: 20451404 (View on PubMed)

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.

Reference Type RESULT
PMID: 19230772 (View on PubMed)

Gore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, Hellstrom-Lindberg E, Swern AS, Beach CL, List AF. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013 Jul;98(7):1067-72. doi: 10.3324/haematol.2012.074831. Epub 2013 Apr 12.

Reference Type DERIVED
PMID: 23585522 (View on PubMed)

Related Links

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http://www.clinicaltrials.gov/ct2/show/NCT01186939?term=NCT01186939&rank=1

Study record for the extension study of AZA PH GL 2003 CL 001

Other Identifiers

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AZA PH GL 2003 CL001

Identifier Type: -

Identifier Source: org_study_id

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