Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01074047
First received: February 16, 2010
Last updated: February 10, 2015
Last verified: February 2015
Results First Received: January 22, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: 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
Participants who were at least 65 years old were randomized in a 1:1 ratio to receive either azacitidine or a conventional care regimen (CCR) as assigned by the physician prior to randomization. Participants randomized to a conventional care treatment arm were assigned to best supportive care, low-dose cytarabine, or intensive chemotherapy.

Reporting Groups
  Description
Azacitidine Azacitidine 75 mg/m^2/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 physicians discretion.
Conventional Care Regimens (CCR)

CCRs included:

  • 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. 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 2 periods

Period 1:   Treatment Phase
    Azacitidine     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     0     0  
NOT COMPLETED     241     247  
Adverse Event                 89                 66  
Disease progression                 16                 21  
Withdrawal by Subject                 27                 48  
Death                 53                 58  
Lost to Follow-up                 0                 1  
Study closure                 24                 13  
Protocol Violation                 0                 1  
Unspecified                 32                 39  
[1] 5 patients not treated with any drug regimen
[2] 7 patients not treated with any drug regimen
[3] Includes those who received one dose of study medication and had one post dose safety assessment
[4] Those with no major protocol violations, given 1 cycle of therapy, and had 1 efficacy assessment

Period 2:   Survival Follow-Up Phase
    Azacitidine     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  
Those who remain alive at study closure                 1                 3  



  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 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 Azacitidine 75 mg/m^2/day subcutaneously [SC] for 7 days every 28 days, allowing for a rest period of 21 days (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and transfusions, per investigator discretion.
Conventional Care Regimens

CCRs included:

  • 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. 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
Total Total of all reporting groups

Baseline Measures
    Azacitidine     Conventional Care Regimens     Total  
Number of Participants  
[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  
Gender  
[units: participants]
     
Female     102     98     200  
Male     139     149     288  
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  
World Health Organization Acute Myeloid Leukemia (AML) Classification [2]
[units: participants]
     
AML with myelodysplasia-related changes     75     83     158  
Therapy-related myeloid neoplasms     8     12     20  
AML with recurrent genetic abnormalities     5     9     14  
AML not otherwise specified     153     143     296  
Bone Marrow-Blasts Counts [3]
[units: Percentage of Bone Marrow Blasts]
Mean ± Standard Deviation
  66.6  ± 24.71     70.2  ± 22.28     68.5  ± 23.56  
[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)
[2]

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.
[3] 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 From Any Cause   [ 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:   Overall Remission Rate (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:   Cytogenetic Complete Remission Rate (CRc-10) 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 22 Jan 2014; Up to 40 months ]

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): Rate of Inpatient Hospitalizations   [ Time Frame: Day 1 (randomization) to 40 months ]

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

31.  Secondary:   HRU: Rate of 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 ]


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


No publications provided


Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01074047     History of Changes
Other Study ID Numbers: AZA-AML-001
Study First Received: February 16, 2010
Results First Received: January 22, 2015
Last Updated: February 10, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Canada: Ethics Review Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Institutional Review Board
Australia: Human Research Ethics Committee
Austria: Ethikkommission
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ethics Commission
Israel: Ministry of Health
Italy: Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Ethics Committee
Poland: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Comité Ético de Investigación Clínica
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Taiwan: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
China: Food and Drug Administration