Myelodysplastic SyndromesPhase 3NCT00071799
A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care
A Phase 3 study testing Azacitidine and Physician Choice in people with Myelodysplastic Syndromes, run by Celgene at 108 sites in 15 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Azacitidine and Physician Choice
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 358 participants
- Where
- 108 sitesin 15 countries
- Study dates
- 1 Nov 2003to 1 Jul 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 13Show fewer
- 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
Trial locations and contacts
108 sites in 15 countries.
108 sites in 15 countries
Germany12 sites
Universitatsklinikum Bonn
Bonn, 53105
Klinikum Chemnitz gGmbH
Chemnitz, 9113
Universitatsklinikum Carl Gustav Carus
Dresden, 1307
St Johannes Hospital
Duisburg, 47166
Heinrich-Heine University Dusseldorf
Düsseldorf, 40225
University Essen
Essen, 45147
Gerorg-August-Universitat Gottingen
Göttingen, 37075
Allgemeines Krankenhaus St. Georg
Hamburg, D-20099
Universitatsklinikum Hambur-Eppendorf
Hamburg, D-20246
Universitatsklinikum Benjamin Franklin
Hindenburgdamm, State of Berlin, D-12203
Universitatsklinikum Kiel II
Kiel, D-24116
Universitatsklinikum Ulm
Ulm, 89070
Spain11 sites
Hospital Santa Creu I Sant Pau
Barcelona, 08025
Hospital Clinic
Barcelona, 08036
Hospital Universitario Germans Trias I Pujol
Barcelona
Hospital de Leon
León, 24071
Hospital Universitario De La Princesa
Madrid, 28006
Hospital Ramon Y Cajal
Madrid, 28034
Hospital La Paz, Madrid
Madrid, 28046
Hospital Clinico San Carlos
Madrid, 28048
Hospital Son Llatzer
Palma de Mallorca, 07198
Hospital Universitario Del Salamanca
Salamanca, 37007
Hospital Universitario La Fe
Valencia, 46009
Australia10 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Peter MacCallum Cancer Institute
East Melbourne, Victoria, 3002
Royal Brisbane Hospital
Hersten, Queensland, 4029
Liverpool Hospital
Liverpool, New South Wales, 2170
Royal Melbourne Hospital
Melbourne, Victoria, 3050
The Alfred Hospital
Melbourne, Victoria, 3181
The Royal Perth Hospital
Perth, Western Australia, 6847
Royal North Shore Hospital
St Leonards, New South Wales, 2065
The Newcastle Mater Miseriecordiae Hospital
Warratah, New South Wales, 2298
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
France10 sites
Chu D'Angers
Angers, 49033
Hopital Beaujon
Clichy, 92110
Che De Lille
Lille, 59037
Hospital Edouard Herriot
Lyon, 69437
Institute Paoli Calmettes
Marseille, 13009
Chu De Nantes
Nantes, 44093
Hospital Saint Louis
Paris, 75010
Hopital Cochin
Paris, 75679
Centre Henri Becquerel
Rouen, 76038
Chu Purpan
Toulouse, 31059
Italy10 sites
Policlinico S. Orsola-Malpighi
Bologna, 40138
Universita di Firenze
Florence, 50139
Ospedale San Martino
Genova, I-16132
Instituto Nazionale Dei Tumori
Milan, 20133
Centro Oncologico Modenese
Modena, 41100
Ospedale San Eugenio
Roma, 00144
Policlinico Gemelli
Roma, 00168
Instituto Nazionale Tumori "Regina Elena"
Roma, 144
Ospedale Casa Sollievo Della Sofferenza - Irrc
San Giovanni Rotondo, 71013
Universita Degli Studi Di Sassari
Sassari, 7100
United States8 sites
University of Alabama School of Medicine
Birmingham, Alabama, 35294
Case Western Reserve University
Cleveland, Ohio, 44106
Indiana University Cancer Center
Indianapolis, Indiana, 46202
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226
Mount Sinai Medical Center
New York, New York, 10029-6574
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, 15224
Oregon Cancer Center
Portland, Oregon, 97201
Washington University School of Medicine
St Louis, Missouri, 63110
Russia7 sites
Burdenko Central Military Clinical Hospital
Moscow, 105299
Blokhin Cancer Research Center
Moscow, 115487
Scientific Haematology Center, Moscow
Moscow, 125167
Institute of Haematology & Blood Transfusion
Saint Petersburg, 193024
Pavlov State Medical University
Saint Petersburg, 197022
Pavlov State Medical University
Saint Petersburg, 197089
City Hospital #31
Saint Petersburg, 197110
United Kingdom7 sites
Royal Bournemouth General Hospital
Bournemouth, BH7 7DW
St. Bartholomew's Hospital
London, EC1A 7BE
Kings College Hospital NHS Trust
London
Christie Hospital
Manchester, M20 4BX
Norfolk and Norwich University Hospital
Norwich, NR4 7UY
John Radcliffe Hospital
Oxford, OX3 9DU
Royal Cornwall Hospital
Truro, TR1 3LJ
Bulgaria6 sites
First Clinical Base - Clinic of Hematology, MHAT - Pleven
Pleven, 5800
MHAT "St George" Clinic of Hematology, Plovdiv
Plovdiv, 4002
III-rd Internal Department, District Dispensary for Oncology diseases with stationary(DDOncDIU)
Plovdiv, 4004
National Centre of Hematology and Transfusiology, Sofia
Sofia, 1756
Multiprofile Hospital for Active Treatment (MHAT), "St. Marina" Clinic of Hematology
Varna, 3010
University Multiprofile Hospital for Active Treatment "Sveta Marina"
Varna, 9010
Greece6 sites
District General Hospital of Athens
Athens, 11527
General Hospital of Chest Disease
Athens, 11527
University Hospital-Attikon
Haidari, Athens, 12462
University General Hospital of Heraklio Voutes
Heraklio, Crete, 71110
University General Hospital of Ioannina
Ioannina, 45500
University General Hospital of Patra Rio
Pátrai, 26500
Poland6 sites
Samodzielny Publiczny Szpital Kliniczny Nr 1
Gdansk, 80-952
Wojewodzki Szpital Specjalistyczny
Lodz, 93-510
Samodzielny Publiczny Szpital Kliniczny
Lublin, 20081
Wojskowy Instytut Medyczny
Warsaw, 00-909
Samodzelny Publiczny Centralny Szpital Kliniczny
Warsaw, 02-097
Samodzielny Publiczny Szpital Kliniczny Nr 1
Wroclaw, 50-367
Czechia5 sites
Fakultni nemocnice Brno
Jihlavska, Brno, 639 00
Fakultni Nemocnice Olomouc
Olomouc, 775 20
Vseobecna Fakultni Nemocnice
Prague, 2 128 08
Uslav Hematologie a Krevni Transfuze
Prague, 2 128 20
Fakultni nemocnice Hradec Kralove
Sokolska, Hradec Kralove, 500 05
Sweden5 sites
Sahlgrenska University Hospital
Gothenburg, S-413 45
Lund Universtiy Hospital
Lund, 22185
University Hospital MAS
Malmö, S-205 02
Huddinge University Hospital
Stockholm, 14186
Uppsala University Hospital
Uppsala, S-751 85
Hungary3 sites
Orszagos Gyogyintezeti Kozpont
Budapest, 1135
University of Pecs, 1st Dept of Internal Medicine
Pécs, 7624
University of Szeged, 2nd Department of Internal Medicine
Szeged, 6701
Netherlands2 sites
VU University Medical Center Amsterdam
Amsterdam, 1081 HV
Univ Hospital St. Radboud
Nijmejen
About this study
Official title: A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)
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.
Read the detailed description
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
- Myelodysplastic Syndromes
- Being tested
- Azacitidine, Physician Choice
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called AZA
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.
Physician ChoiceOther
Also called cytarabine, anthracycline
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
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine | Experimental | Study Drug plus best supportive care. Treatment with erythropoietin was not permitted Receives: Drug: Azacitidine |
| Conventional Care | Active comparator | 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 Receives: Other: Physician Choice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Measured: Day 1 (randomization) to 42 months
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.
Measured: Day 1 (randomization) to 42 months
Number of Participants Who Died
Count of participants who died during the study
Measured: 42 months
Secondary outcomes (12)
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up.
Measured: Day 1 (randomization) to 42 months
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death.
Measured: Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Measured: Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Measured: Day 1 (randomization) to 42 months
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Measured: Day 1 (randomization) to 42 months
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.
Measured: Day 1 (randomization) to 42 months
Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
Investigator determined responses followed IWG criteria for
- complete remission(CR): repeat bone marrow show <5% myeloblasts, and peripheral blood evaluations lasting >=2 months of hemoglobin(>110 g/L), neutrophils(>=1.5x10^9/L), platelets(>=100x10^9/L), blasts (0%) and no dysplasia
- partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment
- stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months.
Measured: Day 1 to 42 months
Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
IWG 2000 Criteria: Pretreatment=hemoglobin <100g/L or RBC transfusion-dependent, platelet count <100x10^9/L or platelet transfusion dependent, absolute neutrophil count <1.5x10^9/L.
Erythroid response: Major->20g/L increase or transfusion independent. Minor- 10-20g/L increase or >=50% decrease in transfusion requirements.
Platelet response: Major-absolute increase of >=30x10^9/L or platelet transfusion independence. Minor->=50% increase.
Neutrophil response: Major->=100% increase or an absolute increase of >0.5x10^9/L. Minor->=100% increase and absolute increase of <0.5x10^9/L.
Measured: Day 1 to 42 months
Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause.
Measured: Day 1 (randomization) to 42 months
Duration of Any Hematologic Improvement
The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause.
Measured: Day 1 (randomization) to 42 months
Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit.
Measured: Day 1 (randomization) to 42 months
Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments.
Measured: Day 1 (randomization) to 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2003 (estimated)
- Study start1 Nov 2003
- Primary completion1 Jul 2007
- Study completion1 Jul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 358 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- CL Beach, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00071799
- Sponsor's protocol ID
- AZA PH GL 2003 CL001
- Status last verified
- Oct 2019
- First submitted
- 31 Oct 2003
- Last updated
- 29 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20026804Fenaux 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.
PubMed 20136825Santini 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.
PubMed 20394651Seymour 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.
PubMed 20451404Fenaux 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.
PubMed 19230772Gore 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.
PubMed 23585522
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)
- ClinicalTrials.gov ID
- NCT00071799
- Acronym / sponsor ID
- AZA PH GL 2003 CL001
- Conditions
- Myelodysplastic Syndromes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 358 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2003 (actual)
- Primary completion
- 1 Jul 2007 (actual)
- Study completion
- 1 Jul 2007 (actual)
- First posted
- 5 Nov 2003 (estimated)
- Results
- Posted 5 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azacitidine | Experimental | Drug: AzacitidineStudy Drug plus best supportive care. Treatment with erythropoietin was not permitted |
| Conventional Care | Active comparator | Other: Physician ChoicePhysician 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- Secondary myelodysplastic syndromes (MDS)
- Prior treatment with azacitidine;
- Prior history of acute myeloid leukemia (AML);
- Malignant disease diagnosed within prior 12 months;
- Metastatic disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: AZAAzacitidine 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. | Drug | Azacitidine |
| Physician ChoiceAlso: cytarabine, anthracyclinePhysician 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 | Other | Conventional Care |
Primary outcome
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Time frame: Day 1 (randomization) to 42 months
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Time frame: Day 1 (randomization) to 42 months
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.
Number of Participants Who Died
Time frame: 42 months
Count of participants who died during the study
12 secondary outcomes
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
Time frame: Day 1 (randomization) to 42 months
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
Time frame: Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Time frame: Day 1 (randomization) to 42 months
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Time frame: Day 1 (randomization) to 42 months
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Time frame: Day 1 (randomization) to 42 months
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Time frame: Day 1 (randomization) to 42 months
Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
Time frame: Day 1 to 42 months
Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
Time frame: Day 1 to 42 months
Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
Time frame: Day 1 (randomization) to 42 months
Duration of Any Hematologic Improvement
Time frame: Day 1 (randomization) to 42 months
Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
Time frame: Day 1 (randomization) to 42 months
Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Time frame: Day 1 (randomization) to 42 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20026804Fenaux 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.
- Results publication: PubMed 20136825Fenaux 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.
- Results publication: PubMed 20394651Santini 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.
- Results publication: PubMed 20451404Seymour 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.
- Results publication: PubMed 19230772Fenaux 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.
- Derived from this study: PubMed 23585522Gore 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.
- Study record for the extension study of AZA PH GL 2003 CL 001Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
CL Beach study director
Celgene Corporation
108 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azacitidine and Physician Choice in people with Myelodysplastic Syndromes, run by Celgene at 108 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 108 sites in Germany, Spain, Australia, France, Italy and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kaplan-Meier Estimates for Median Time to Death From Any Cause (time frame: Day 1 (randomization) to 42 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00071799, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2019.