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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00071799




Registration number
NCT00071799
Ethics application status
Date submitted
31/10/2003
Date registered
5/11/2003
Date last updated
29/10/2019

Titles & IDs
Public title
A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care
Scientific 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)
Secondary ID [1] 0 0
AZA PH GL 2003 CL001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Other interventions - Physician Choice

Experimental: Azacitidine - Study Drug plus best supportive care. Treatment with erythropoietin was not permitted

Active comparator: 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


Treatment: Drugs: 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.

Other interventions: 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 code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Timepoint [1] 0 0
Day 1 (randomization) to 42 months
Primary outcome [2] 0 0
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
Timepoint [2] 0 0
Day 1 (randomization) to 42 months
Primary outcome [3] 0 0
Number of Participants Who Died
Timepoint [3] 0 0
42 months
Secondary outcome [1] 0 0
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
Timepoint [1] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [2] 0 0
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
Timepoint [2] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [3] 0 0
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Timepoint [3] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [4] 0 0
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Timepoint [4] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [5] 0 0
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Timepoint [5] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [6] 0 0
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Timepoint [6] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [7] 0 0
Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
Timepoint [7] 0 0
Day 1 to 42 months
Secondary outcome [8] 0 0
Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
Timepoint [8] 0 0
Day 1 to 42 months
Secondary outcome [9] 0 0
Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
Timepoint [9] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [10] 0 0
Duration of Any Hematologic Improvement
Timepoint [10] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [11] 0 0
Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
Timepoint [11] 0 0
Day 1 (randomization) to 42 months
Secondary outcome [12] 0 0
Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Timepoint [12] 0 0
Day 1 (randomization) to 42 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [3] 0 0
The Newcastle Mater Miseriecordiae Hospital - Warratah
Recruitment hospital [4] 0 0
Royal Brisbane Hospital - Hersten
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [9] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [10] 0 0
The Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
2298 - Warratah
Recruitment postcode(s) [4] 0 0
4029 - Hersten
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3002 - East Melbourne
Recruitment postcode(s) [8] 0 0
3050 - Melbourne
Recruitment postcode(s) [9] 0 0
3181 - Melbourne
Recruitment postcode(s) [10] 0 0
6847 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Pleven
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Plovdiv
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Varna
Country [13] 0 0
Czechia
State/province [13] 0 0
Brno
Country [14] 0 0
Czechia
State/province [14] 0 0
Hradec Kralove
Country [15] 0 0
Czechia
State/province [15] 0 0
Olomouc
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha
Country [17] 0 0
France
State/province [17] 0 0
Angers
Country [18] 0 0
France
State/province [18] 0 0
Clichy
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Lyon
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
France
State/province [22] 0 0
Nantes
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Rouen
Country [25] 0 0
France
State/province [25] 0 0
Toulouse
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Bonn
Country [28] 0 0
Germany
State/province [28] 0 0
Chemnitz
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Duisburg
Country [31] 0 0
Germany
State/province [31] 0 0
Dusseldorf
Country [32] 0 0
Germany
State/province [32] 0 0
Essen
Country [33] 0 0
Germany
State/province [33] 0 0
Gottingen
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Kiel
Country [36] 0 0
Germany
State/province [36] 0 0
Ulm
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Greece
State/province [38] 0 0
Crete
Country [39] 0 0
Greece
State/province [39] 0 0
Ioannina
Country [40] 0 0
Greece
State/province [40] 0 0
Patra
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
Country [42] 0 0
Hungary
State/province [42] 0 0
Pecs
Country [43] 0 0
Hungary
State/province [43] 0 0
Szeged
Country [44] 0 0
Italy
State/province [44] 0 0
Bologna
Country [45] 0 0
Italy
State/province [45] 0 0
Firenze
Country [46] 0 0
Italy
State/province [46] 0 0
Genova
Country [47] 0 0
Italy
State/province [47] 0 0
Milano
Country [48] 0 0
Italy
State/province [48] 0 0
Modena
Country [49] 0 0
Italy
State/province [49] 0 0
Roma
Country [50] 0 0
Italy
State/province [50] 0 0
San Giovanni Rotondo
Country [51] 0 0
Italy
State/province [51] 0 0
Sassari
Country [52] 0 0
Netherlands
State/province [52] 0 0
Amsterdam
Country [53] 0 0
Netherlands
State/province [53] 0 0
Nijmejen
Country [54] 0 0
Poland
State/province [54] 0 0
Gdansk
Country [55] 0 0
Poland
State/province [55] 0 0
Lodz
Country [56] 0 0
Poland
State/province [56] 0 0
Lublin
Country [57] 0 0
Poland
State/province [57] 0 0
Warszawa
Country [58] 0 0
Poland
State/province [58] 0 0
Wroclaw
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Moscow
Country [60] 0 0
Russian Federation
State/province [60] 0 0
St. Petersburg
Country [61] 0 0
Spain
State/province [61] 0 0
Barcelona
Country [62] 0 0
Spain
State/province [62] 0 0
Leon
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Palma de Mallorca
Country [65] 0 0
Spain
State/province [65] 0 0
Salamanca
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia
Country [67] 0 0
Sweden
State/province [67] 0 0
Goteborg
Country [68] 0 0
Sweden
State/province [68] 0 0
Lund
Country [69] 0 0
Sweden
State/province [69] 0 0
Malmo
Country [70] 0 0
Sweden
State/province [70] 0 0
Stockholm
Country [71] 0 0
Sweden
State/province [71] 0 0
Uppsala
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Bournemouth
Country [73] 0 0
United Kingdom
State/province [73] 0 0
London
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Manchester
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Norwich
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Oxford
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
CL Beach
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents