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Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01201811
First received: September 13, 2010
Last updated: June 25, 2014
Last verified: June 2014
Results First Received: May 21, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Myelodysplastic Syndromes
Intervention: Drug: Azacitidine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at nine investigational sites within Taiwan. The purpose of the current study was to evaluate the efficacy, safety, and steady-state Pharmacokinetic (PK) profile of subcutaneous (SC) azacitidine given at a dose of 75 mg/m^2/day for 7 days in Taiwanese participants with higher-risk Myelodysplastic Syndrome (MDS).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Azacitidine Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles

Participant Flow:   Overall Study
    Azacitidine  
STARTED     44  
COMPLETED     25  
NOT COMPLETED     19  
Adverse Event                 6  
Disease progression                 3  
Withdrawal by Subject                 3  
Death                 4  
Treatment Failure                 2  
Physician Decision                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The intention-to-treat (ITT) population was defined as all enrolled participants.

Reporting Groups
  Description
Azacitidine Azacitidine 75 mg/m^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles

Baseline Measures
    Azacitidine  
Number of Participants  
[units: participants]
  44  
Age  
[units: years]
Mean ± Standard Deviation
  62.3  ± 11.76  
Gender  
[units: participants]
 
Female     17  
Male     27  
Race/Ethnicity, Customized [1]
[units: participants]
 
Asian     44  
Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification [2]
[units: participants]
 
Refractory anemia with excess blasts (RAEB)     35  
RAEB in transformation     7  
Chronic myelomonocytic leukemia (Modified CMML)     2  
Acute myelogenous leukemia (AML)     0  
World Health Organization (WHO) Classification [3]
[units: participants]
 
Refractory anemia with excess blasts (RAEB-1)     15  
Refractory anemia with excess blasts (RAEB-2)     23  
Acute myelogenous leukemia (AML)     5  
Chronic myelomonocytic leukemia (CMML -1)     1  
Chronic myelomonocytic leukemia (CMML-2)     0  
Refractory anemia (RA)     0  
RA with ringed sideroblasts (RARS)     0  
Refractory Cytopenia Multilineage Dysplasia (RCMD)     0  
Myelodysplastic Syndrome - Unclassified (MDS-U)     0  
International Prognostic Scoring System (IPSS) [4]
[units: participants]
 
Low risk (0)     0  
Intermediate-1 (0.5 - 1.0)     2  
Intermediate-2 (1.5 - 2.0)     16  
High Risk (≥ 2.5)     26  
[1] Taiwanese origin
[2] FAB is a classification system for five (5) subtypes of myelodysplastic syndrome that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts or a monocytosis. Classification was made by the Local Reviewer.
[3] The World Health Organization (WHO) classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.
[4] The international prognostic scoring system (IPSS) is a standard for risk assessment in primary myelodysplastic syndromes (MDS) that categorizes prognoses taking into account cytogenetics, cytopenias, blasts and blood counts. The IPSS prognostic subgroups consist of low-, intermediate-1-, intermediate-2-, and high-risk groups. The scale is 0-3.5 at 0.5 increments. Scores of 0=Low; 0.5-1.0=Int-1; 1.5-2.0=Int-2; 2.5-3.5=High risk which corresponds to poorer prognosis. The assessment was performed by the local investigator



  Outcome Measures
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1.  Primary:   Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator   [ Time Frame: Response assessed at end of cycle 6; through week 24; End of study ]

2.  Primary:   Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor   [ Time Frame: Response assessed at end of cycle 6; through week 24; End of study ]

3.  Secondary:   Number of Red Blood Cell (RBC) Transfusions by Cycle   [ Time Frame: Up to week 24;The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]

4.  Secondary:   Number of Platelet Transfusions by Cycle   [ Time Frame: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]

5.  Secondary:   Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days   [ Time Frame: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]

6.  Secondary:   Number of Participants With Adverse Events (AE)   [ Time Frame: From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days) ]

7.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

8.  Secondary:   Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

9.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

10.  Secondary:   Time to Maximum Plasma Concentration (Tmax) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

11.  Secondary:   Terminal Phase of Half-life (T1/2) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

12.  Secondary:   Apparent Total Plasma Clearance (CL/F) of Azacitidine   [ Time Frame: Timeframe: Days 5 and 6 at predose and Day 7 (pre-dose) at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

13.  Secondary:   Apparent Volume of Distribution (Vd/F) of Azacitidine   [ Time Frame: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose ]

14.  Other Pre-specified:   Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline   [ Time Frame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit ]

15.  Other Pre-specified:   Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline   [ Time Frame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]

16.  Other Pre-specified:   Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline   [ Time Frame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]

17.  Other Pre-specified:   Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline   [ Time Frame: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided


Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01201811     History of Changes
Other Study ID Numbers: AZA-MDS-001
Study First Received: September 13, 2010
Results First Received: May 21, 2014
Last Updated: June 25, 2014
Health Authority: Taiwan : Food and Drug Administration
United States: Food and Drug Administration