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Study of Vidaza Versus Conventional Care Regimens for the Treatment of Acute Myeloid Leukemia (AML)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01074047
First Posted: February 24, 2010
Last Update Posted: August 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene
Results First Submitted: January 22, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Acute Myeloid Leukemia
Interventions: Drug: Azacitidine
Drug: Conventional Care Regimen

  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
This was a multicenter, international Phase 3 study conducted at 107 investigational sites in 18 countries including South Korea, China, Taiwan, Australia, Canada, United States, Poland, Russia, Czech Republic, Israel, France, Italy, Spain, Germany, United Kingdom, Belgium, Austria and the Netherlands.

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 (AZA) Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
Conventional Care Regimens (CCR)

CCRs included:

  • 1 Intensive Chemotherapy: Cytarabine 100-200 mg/m2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m² QD or Idarubicin 9-12 mg/m² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed
  • 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC
  • 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help

Participant Flow for 3 periods

Period 1:   Treatment Phase
    Azacitidine (AZA)   Conventional Care Regimens (CCR)
STARTED   241   247 
Treated Population   236 [1]   240 [2] 
Safety Population   236 [3]   235 [3] 
Evaluable Population   179 [4]   191 [4] 
COMPLETED   24 [5]   13 [5] 
NOT COMPLETED   217   234 
Adverse Event                89                66 
Disease Progression                16                21 
Withdrawal by Subject                27                48 
Death                53                58 
Lost to Follow-up                0                1 
Protocol Violation                0                1 
Miscellaneous                32                39 
[1] 5 patients not treated with any drug regimen
[2] 7 patients not treated with any drug regimen
[3] Received at least one dose of study medication and had at least 1 post dose safety assessment
[4] Did not meet criteria for exclusion, received ≥1 cycle of treatment and had ≥ 1 efficacy assessment
[5] Participants who were continuing study treatment at the time of study closure

Period 2:   Survival Follow-Up Phase
    Azacitidine (AZA)   Conventional Care Regimens (CCR)
STARTED   140   163 
COMPLETED   16   27 
NOT COMPLETED   124   136 
Withdrawal by Subject                5                8 
Lost to Follow-up                2                1 
Death                116                124 
Alive at study closure                1                3 

Period 3:   Extension Phase
    Azacitidine (AZA)   Conventional Care Regimens (CCR)
STARTED   22 [1]   0 
Safety Population   22 [2]   0 
COMPLETED   0   0 
NOT COMPLETED   22   0 
Physician Decision                1                0 
Adverse Event                5                0 
Disease Progression                9                0 
Withdrawal by Subject                2                0 
Death                5                0 
[1] 2 participants did not enroll in the extension period.
[2] Participants who enrolled in the extension phase



  Baseline Characteristics
  Hide Baseline Characteristics

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 intent-to-treat (ITT) population is defined as all participants who were randomized, independent of whether they received study treatment or not.

Reporting Groups
  Description
Azacitidine (AZA) Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
Conventional Care Regimens (CCR) #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. Consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed. # 2 Low-dose cytarabine 20 mg SC twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only includes transfusion of blood products, antibiotics, antifungals and nutritional help.
Total Total of all reporting groups

Baseline Measures
   Azacitidine (AZA)   Conventional Care Regimens (CCR)   Total 
Overall Participants Analyzed 
[Units: Participants]
 241   247   488 
Age 
[Units: Years]
Mean (Standard Deviation)
 75.4  (5.60)   75.1  (5.57)   75.2  (5.58) 
Age, Customized 
[Units: Participants]
     
<75 years   103   120   223 
≥75 years   138   127   265 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      102  42.3%      98  39.7%      200  41.0% 
Male      139  57.7%      149  60.3%      288  59.0% 
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
     
0 = Fully Active   54   57   111 
1 = Restrictive but Ambulatory   132   132   264 
2 = Ambulatory but unable to work   55   58   113 
3 = Limited Self Care   0   0   0 
4 = Completely disabled   0   0   0 
[1] ECOG performance status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity), 1 = Restricted activity but ambulatory, 2 = Ambulatory but unable to carry out work activities, 3 = Limited Self Care; 4 = Completely Disabled, No self care (Least Favorable Activity)
World Health Organization Acute Myeloid Leukemia (AML) Classification [1] 
[Units: Participants]
     
AML with myelodysplasia-related changes   75   83   158 
Therapy-related myeloid neoplasms   8   12   158 
AML with recurrent genetic abnormalities   5   9   14 
AML not otherwise specified   153   143   296 
[1]

WHO categories include:

  1. Those with AML with recurrent genetic abnormalities. Includes subtypes with multiple chromosome translocations and mutations.
  2. Those with AML with myelodysplasia-related changes. Includes those with prior myelodysplastic syndrome (MDS) or myeloproliferative disease and has transformed to AML.
  3. Those with therapy related myeloid neoplasms and have had prior chemotherapy and/or radiation and subsequently develop AML or MDS
  4. Those with AML not otherwise specified and include subtypes that do not fall into the above categories.
Bone Marrow-Blasts Counts [1] 
[Units: Percentage of Bone Marrow Blasts]
Mean (Standard Deviation)
 66.6  (24.71)   70.2  (22.28)   68.5  (23.56) 
[1] Baseline clinical characteristics, including percentage of bone marrow blasts were assessed centrally and locally. Central values are included here. Baseline blasts were the last non-missing value on or prior to the date of randomization. The bone marrow blasts cells are not typically found in the circulating blood of healthy individuals. Abnormal immature white blood cells (blasts) fill the bone marrow and spill into the bloodstream.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Kaplan-Meier Estimates for Overall Survival   [ Time Frame: Day 1 (randomization) to 40 months ]

2.  Secondary:   One-year Overall Survival Rate   [ Time Frame: From Day 1 (randomization) to 40 months ]

3.  Secondary:   Event-free Survival (EFS)   [ Time Frame: Day 1 (randomization) to date of treatment failure, progressive disease, relapse after Complete Remission (CR) or Complete remission with incomplete blood count recovery (CRi), death from any cause. Day 1 (randomization) to 40 months ]

4.  Secondary:   Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)   [ Time Frame: Day 1 of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up. Day 1 (randomization) to 40 months ]

5.  Secondary:   Percentage of Participants Who Achieved a Morphologic CR + CRi as Determined by the Independent Review Committee (IRC) Based on International Working Group (IWG) Response Criteria for Acute Myeloid Leukemia (AML)   [ Time Frame: Day 1 (randomization) to 40 months ]

6.  Secondary:   Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates   [ Time Frame: Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse. ]

7.  Secondary:   Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.   [ Time Frame: Day 1 (randomization) to 40 months ]

8.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017 ]

9.  Secondary:   Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain   [ Time Frame: Baseline to Cycle 3; at approximately 3 months ]

10.  Secondary:   Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain   [ Time Frame: Baseline to Cycle 5, at approximately 5 months ]

11.  Secondary:   Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain   [ Time Frame: Baseline to Cycle 7, at approximately 7 months ]

12.  Secondary:   Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain   [ Time Frame: Baseline to Cycle 9, at approximately 9 months ]

13.  Secondary:   Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain   [ Time Frame: Baseline to End of Study; at approximately 11-12 months ]

14.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea   [ Time Frame: Baseline to Cycle 3, at approximately 3 months ]

15.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea   [ Time Frame: Baseline to Cycle 5, at approximately 5 months ]

16.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea   [ Time Frame: Baseline to Cycle 7, at approximately 7 months ]

17.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea   [ Time Frame: Baseline to Cycle 9, at approximately 9 months ]

18.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea   [ Time Frame: Baseline to end of study, at approximately 11-12 months ]

19.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Baseline to Cycle 3, at approximately 3 months ]

20.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Baseline to Cycle 5, at approximately 5 months ]

21.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Baseline to Cycle 7, at approximately 7 months ]

22.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Baseline to Cycle 9, at approximately 9 months ]

23.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain   [ Time Frame: Baseline to end of study, at approximately 11-12 months ]

24.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain   [ Time Frame: Baseline to Cycle 3, at approximately 3 months ]

25.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain   [ Time Frame: Baseline to Cycle 5, at approximately 5 months ]

26.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain   [ Time Frame: Baseline to Cycle 7, at approximately 7 months ]

27.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain   [ Time Frame: Baseline to Cycle 9, at approximately 9 months ]

28.  Secondary:   HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain   [ Time Frame: Baseline to end of study, at approximately 11-12 months ]

29.  Secondary:   Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations   [ Time Frame: Day 1 (randomization) to 40 months ]

30.  Secondary:   Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year   [ Time Frame: Day 1 (randomization) to 40 months ]

31.  Secondary:   HRU: Number of Participants Receiving Transfusions   [ Time Frame: Day 1 (randomization) to 40 months ]

32.  Secondary:   HRU: Rate of Transfusions Per Patient Year   [ Time Frame: Day 1 (randomization) to 40 months ]

33.  Secondary:   Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)   [ Time Frame: From the date of informed consent for the Extension Phase through to the date of last dose of study drug + 28 days up to last visit completed 24 July 2016; maximum duration of exposure to Azacitidine was 871 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
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  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, Senior Manager Clinical Trial Disclosure
Organization: Celgene
phone: 888-260-1599
e-mail: ClinicalTrialDisclosure@celgene.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01074047     History of Changes
Other Study ID Numbers: AZA-AML-001
First Submitted: February 16, 2010
First Posted: February 24, 2010
Results First Submitted: January 22, 2015
Results First Posted: February 26, 2015
Last Update Posted: August 29, 2017



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