QUAZAR AML-001: Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission
Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01757535
Collaborator
(none)
472
240
2
116.2
2
0
Study Details
Study Description
Brief Summary
This study enrolled 472 participants, aged 55 or older, with a diagnosis of de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or chronic myelomonocytic leukemia (CMML), and who have achieved first complete remission (CR)/ complete remission with incomplete blood count recovery (CRi) following induction with or without consolidation chemotherapy.
The study is amended to include an extension phase (EP). The EP allows participants who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the investigator, to continue receiving oral azacitidine after unblinding by sponsor until the participant meets the criteria for study discontinuation or until oral azacitidine becomes commercially available and reimbursed. In addition, all participants in the placebo arm and participants who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the follow-up phase will be followed for survival in the EP.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is an international, multicenter, placebo-controlled, Phase 3 study with a double-blind, randomized, parallel-group design in subjects with de novo AML or AML secondary to prior diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) aged ≥ 55 years, who are in first CR/CRi following induction therapy with or without consolidation chemotherapy. The study consists of 3 phases; the pre-randomization phase (screening phase), the treatment phase, and the follow-up phase.
The study is amended to include an extension phase (EP). The EP allows participants who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the Investigator, to continue receiving oral azacitidine after unblinding by sponsor until they meet the criteria for study discontinuation or until oral azacitidine becomes commercially available and reimbursed. In addition, all participants in the placebo arm and participants who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the follow-up phase will be followed for survival in the EP.
Study Design
Study Type:
Interventional
Actual Enrollment
:
472 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission
Actual Study Start Date
:
Apr 24, 2013
Actual Primary Completion Date
:
Jul 15, 2019
Anticipated Study Completion Date
:
Dec 31, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Oral Azacitidine 300 mg oral azacitidine on days 1 to 14 of each 28-day treatment cycle. |
Drug: Oral Azacitidine
300 mg oral azacitidine on days 1 to 14 of each 28-day treatment cycle.
Other Names:
|
| Placebo Comparator: Placebo Identically matching placebo tablets on days 1 to 14 of each 28-day treatment cycle. |
Drug: Placebo
Identically matching placebo tablets on days 1 to 14 of each 28-day treatment cycle.
|
Outcome Measures
Primary Outcome Measures
- Kaplan-Meier (K-M) Estimate for Overall Survival (OS) [Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants.]
Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive.
Secondary Outcome Measures
- Kaplan-Meier Estimate of Relapse Free Survival (RFS) [From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months]
RFS was defined as the time from the date of randomization to the date of documented relapse or death from any cause, whichever occurred first. Participants who were still alive without documented relapse, or who were lost to follow-up or withdrew consent without documented relapse, were censored at the date of their last bone marrow assessment, prior to receiving any other therapy for AML. Documented relapse was defined as the earliest date of the following: ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or at least 2 peripheral blasts ≥ 5% within 30 days.
- Kaplan-Meier Estimate of Time to Relapse [Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months]
Time to relapse was defined as the interval (in months) from the date of randomization to the date of documented relapse. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from complete remission (CR)/ complete remission with incomplete blood count recovery (CRi). Documented relapse was defined as, the earliest date of the following: ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or at least 2 peripheral blasts ≥ 5% within 30 days.
- Kaplan-Meier Estimates of Time to Discontinuation From Treatment [From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months]
Time to discontinuation from treatment was assessed and defined as the interval from the date of randomization to the date of discontinuation from study drug. Participants who were receiving treatment at the time of study closure were censored at the date of last visit. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from CR/ CRi.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Day 1 (randomization) to the data cut off date of 15 July 2019; the median treatment duration was 11.6 months (range: 0.5 to 74.3 months) for the oral aza arm and 5.7 months (range: 0.7 to 68.5 months) for the placebo arm.]
TEAEs include AEs that started between first dose date and 28 days after the last dose of study drug. A serious adverse event (SAE) is: Death Life-threatening event Inpatient hospitalization or prolongation of existing hospitalization Persistent or significant disability or incapacity Congenital anomaly or birth defect Other important medical event The severity of AEs were assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: Grade 1 (Mild): asymptomatic/mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Grade 4: Life-threatening; urgent intervention indicated. Grade 5: Death due to AE.
- Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline [Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1]
The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated.
- Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline [Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1]
The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
- Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the FACIT-Fatigue Scale From Baseline [Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1]
A clinically meaningful improvement or worsening was defined as at least 3 points of improvement or worsening from baseline, respectively, for FACIT-Fatigue. The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated.
- Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the EQ-5D-3L Scale From Baseline [Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1]
The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
- Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) [From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months]
Clinically meaningful deterioration was defined as at least 3 points of deterioration from baseline for at least 2 consecutive visits for the FACIT--Fatigue. The FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all to 4 = very much. The scores that range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, subscores were prorated.
- Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale [From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months]
Clinically meaningful deterioration was defined at least 0.10 point of deterioration from baseline for at least 2 consecutive visits for the EQ-5D Health Utility Index. The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The EQ-5D-3L is scored using the UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
- Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year [Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months]
HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
- Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year [Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months]
HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Male or female participants ≥ 55 years of age
-
Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
-
First complete remission (CR)/ complete remission with incomplete blood count recovery (CRi) with induction therapy with intensive chemotherapy with or without consolidation therapy within 4 months (+/- 7 days of achieving CR or CRi)
-
Eastern Cooperative Oncology Group (ECOG) performance status - 0, 1, 2, 3
Key Inclusion Criteria in the Extended Phase of the study:
At the Investigator's discretion and with approval of the sponsor, participants meeting all of the following eligibility criteria are eligible to enter the extension phase:
- All participants randomized into the oral azacitidine or placebo arm and are continuing in either the treatment phase or follow-up phase of the CC-486-AML-001 study;
-
Participants randomized to oral azacitidine treatment arm and continuing in the treatment phase demonstrating clinical benefit as assessed by the investigator are eligible to receive oral azacitidine in the extension phase (EP);
-
Participants randomized into placebo arm of the study will not receive oral azacitidine in the EP, but will be followed for survival in the EP;
-
Participants currently in the follow-up phase will continue to be followed for survival in the EP;
-
Participants who have signed the informed consent for the EP of the study;
-
Participants who do not meet any of the criteria for study discontinuation
Key Exclusion Criteria:
-
AML with inversion (inv)(16), translocation = t(8;21), t(16;16), t(15;17), or t(9;22) or molecular evidence of such translocations
-
Prior bone marrow or stem cell transplantation
-
Have achieved CR/CRi following therapy with hypomethylating agents
-
Diagnosis of malignant disease within the previous 12 months
-
Proven central nervous system (CNS) leukemia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arizona Oncology Associates, P.C. | Phoenix | Arizona | United States | 85016 |
| 2 | Providence St Joseph Medical Center Cancer Center | Burbank | California | United States | 91505 |
| 3 | City of Hope | Duarte | California | United States | 91010-301 |
| 4 | University of California San Francisco Fresno Campus | Fresno | California | United States | 93701 |
| 5 | University of Southern California Norris Cancer Center | Los Angeles | California | United States | 90033 |
| 6 | UCLA | Los Angeles | California | United States | 90095-6956 |
| 7 | UC Irvine | Orange | California | United States | 92868 |
| 8 | Sharp Memorial Hospital | San Diego | California | United States | 92123 |
| 9 | Stanford Cancer Center | Stanford | California | United States | 94305-582 |
| 10 | Innovative Clinical Research Institute | Whittier | California | United States | 90603 |
| 11 | Rocky Mountain Cancer Center | Denver | Colorado | United States | 80218-1210 |
| 12 | The Hospital of Central Connecticut | Southington | Connecticut | United States | 06489 |
| 13 | George Washington University Cancer Center | Washington | District of Columbia | United States | 20037 |
| 14 | University of Florida | Gainesville | Florida | United States | 32610 |
| 15 | Mount Sinai Comprehensive Cancer Center | Miami Beach | Florida | United States | 33140 |
| 16 | University of Florida Health Cancer Center at Orlando Health | Orlando | Florida | United States | 32806 |
| 17 | Northwestern University Medical Center Division of Hematology Oncology | Chicago | Illinois | United States | 60611 |
| 18 | Loyola University Chicago | Maywood | Illinois | United States | 60153 |
| 19 | Cancer Care and Hematology Specialists of Chicagoland, P.C. - Niles, IL | Niles | Illinois | United States | 60714 |
| 20 | Indiana University Cancer Center | Indianapolis | Indiana | United States | 46202-528 |
| 21 | Franciscan St. Francis Health | Indianapolis | Indiana | United States | 46237 |
| 22 | Kansas University Medical Center | Westwood | Kansas | United States | 66205 |
| 23 | University of Louisville | Louisville | Kentucky | United States | 40202 |
| 24 | Norton Cancer Institute Louisville Oncology | Louisville | Kentucky | United States | 40207 |
| 25 | Tulane University Medical Center | New Orleans | Louisiana | United States | 70112 |
| 26 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121-2483 |
| 27 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 28 | University of Massachusetts | Worcester | Massachusetts | United States | 01655 |
| 29 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 30 | Kansas City VA Medical Center University of Kansas Medical Center | Kansas City | Missouri | United States | 64128 |
| 31 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 32 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-7680 |
| 33 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 34 | Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08901 |
| 35 | Winthrop University Hospital | Mineola | New York | United States | 11501-3893 |
| 36 | Mt. Sinai Medical Center | New York | New York | United States | 10029 |
| 37 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 38 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 39 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 40 | New York Medical College | Valhalla | New York | United States | 10595 |
| 41 | Duke University Medical Center | Durham | North Carolina | United States | 27705 |
| 42 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | 27157 |
| 43 | University Hospitals Case Medical Center | Cleveland | Ohio | United States | 44106 |
| 44 | University of Oklahoma Peggy and Charles Stephenson Cancer Center | Oklahoma City | Oklahoma | United States | 73104 |
| 45 | Kaiser Permanente Northwest Oncology Hematology | Portland | Oregon | United States | 97227 |
| 46 | Lancaster General Hospital | Lancaster | Pennsylvania | United States | 17604 |
| 47 | UPMC Cancer Pavillion | Pittsburgh | Pennsylvania | United States | 15232 |
| 48 | Greenville Hospital System | Greenville | South Carolina | United States | 29605 |
| 49 | Sarah Cannon Research Inst | Nashville | Tennessee | United States | 37203 |
| 50 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232-5505 |
| 51 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390-9068 |
| 52 | Brooke-Army Medical Center | Fort Sam Houston | Texas | United States | 78234 |
| 53 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 54 | Cancer Care Centers of South Texas - Loop | San Antonio | Texas | United States | 78217 |
| 55 | Methodist Hospital | San Antonio | Texas | United States | 78229 |
| 56 | VA Commonwealth University Massey Cancer Center | Richmond | Virginia | United States | 23298-0037 |
| 57 | Swedish Cancer Inst | Seattle | Washington | United States | 98104 |
| 58 | Yakima Valley Memorial Hospital/ North Star Lodge | Yakima | Washington | United States | 98902 |
| 59 | Froedtert Hospital BMT Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226-3522 |
| 60 | Mater Private Medical Centre Haematology and Oncology Clinics of Australasia Research Centre | South Brisbane | Queensland | Australia | 4101 |
| 61 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | SA 5000 |
| 62 | Flinders Medical Centre, Dept Of Oncology | Bedford Park | South Australia | Australia | 5042 |
| 63 | Austin Hospital | Heidelberg | Australia | 3084 | |
| 64 | Royal Hobart Hospital | Hobart | Australia | 7000 | |
| 65 | Liverpool Hospital | Liverpool | Australia | 2170 | |
| 66 | The Alfred Hospital | Melbourne | Australia | 3004 | |
| 67 | Royal Perth Hospital | Perth | Australia | 6000 | |
| 68 | Local Institution - 506 | St Leonards | Australia | 2065 | |
| 69 | Royal North Shore Hospital | St Leonards | Australia | 2065 | |
| 70 | Wollongong Hospital | Wollongong | Australia | 2500 | |
| 71 | The Queen Elizabeth Hospital | Woodville South | Australia | 5011 | |
| 72 | Local Institution - 501 | Woolloongabba | Australia | 4102 | |
| 73 | Princess Alexandra Hospital | Woolloongabba | Australia | 4102 | |
| 74 | Medical University of Graz | Graz | Austria | A-8036 | |
| 75 | University Hospital of Salzburg | Salzburg | Austria | 5020 | |
| 76 | KH Hietzing | Vienna | Austria | 1130 | |
| 77 | Medical University of Vienna | Vienna | Austria | 1190 | |
| 78 | Hanusch Krankenhaus | Wien | Austria | 1140 | |
| 79 | AZ St-Jan Brugge Oostende AV | Brugge | Belgium | 8000 | |
| 80 | Grand Hopital de Charleroi | Charleroi | Belgium | 6000 | |
| 81 | Center Hospitalier Universitaire Ambroise Pare | Mons | Belgium | 7000 | |
| 82 | Hospital de Clínicas de Porto Alegre | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 83 | Local Institution - 231 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 84 | Hospital Erasto Gaertner | Curitiba | Brazil | 81520-060 | |
| 85 | Instituto Nacional de Cancer - INCA | Rio de Janeiro | Brazil | 20230-130 | |
| 86 | Saint Petersburg Medical State Institution Municipal n.a. I.P. Pavlov | Saint Petersburg | Brazil | 196022 | |
| 87 | Hospital Albert Einstein Sociedade Beneficente Israelita Brasileira | Sao Paulo | Brazil | 05651-901 | |
| 88 | Sociedade Beneficente de Senhoras Hospital Sirio Libanes | São Paulo | Brazil | 01308-050 | |
| 89 | University of Alberta | Edmonton | Alberta | Canada | T6G 2B7 |
| 90 | Cancer Care Manitoba | Winnipeg | Manitoba | Canada | R3E OV9 |
| 91 | Regional Health Authority B-Saint John Regional Hospital | Saint John | New Brunswick | Canada | E2L 4L2 |
| 92 | Health Sciences Center | St John's | Newfoundland and Labrador | Canada | A1B3V6 |
| 93 | Queen Elizabeth II Health Sciences Center | Halifax | Nova Scotia | Canada | B3H 2Y9 |
| 94 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 95 | Local Institution - 608 | Montreal | Quebec | Canada | H2W 1S6 |
| 96 | McGill University, Dept. Oncology Clinical Research Program | Montreal | Quebec | Canada | H2W 1S6 |
| 97 | Hopital du Sacre-Coeur de Montreal | Montreal | Quebec | Canada | H4J 1C5 |
| 98 | Fakultni nemocnice Brno | Brno | Czechia | 625 00 | |
| 99 | Local Institution - 321 | Praha | Czechia | 128 08 | |
| 100 | Vseobecna Fakultni Nemocnice v Praze | Praha | Czechia | 128 08 | |
| 101 | Ustav hematologie a krevni transfuze | Praha | Czechia | 128 20 | |
| 102 | Helsinki University Central Hospital | Helsinki | Finland | 290 | |
| 103 | University HospitaClinik of internal medicin | Tampere | Finland | 33521 | |
| 104 | Turku University Hospital | Turku | Finland | 20521 | |
| 105 | Hopital Sud, CHU d'Amiens | Amiens | France | 80054 | |
| 106 | CH Argenteuil Victor Dupouy | Argenteuil | France | 95100 | |
| 107 | Hopital Avicenne | Bobigny Cedex | France | 93009 | |
| 108 | Centre hospitalier de Boulognes - Duchenne | Boulognes Sur Mer | France | 62200 | |
| 109 | Hopital dinstruction des armees Percy | Clamart Cedex | France | 92141 | |
| 110 | Hopital Henri Mondor | Creteil | France | 94010 | |
| 111 | Centre Hospitalier de Versailles Hopital Andre Mignot | Le Chesnay Cedex | France | 78157 | |
| 112 | CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang | Lille | France | 59037 | |
| 113 | Local Institution - 453 | Lille | France | 59037 | |
| 114 | CHU Limoges | Limoges Cedex | France | 87042 | |
| 115 | CHU Hopital Edouard Herriot | Lyon cedex | France | 69437 | |
| 116 | Hopital Saint Louis | Paris Cedex 10 | France | 75475 | |
| 117 | Hospital of Necker | Paris | France | 75015 | |
| 118 | Hopital Saint Louis | Paris | France | 75475 | |
| 119 | Centre Hospitalier Pontoise Rene Dubos | Pontoise | France | 95301 | |
| 120 | Centre Henri Becquerel | Rouen | France | 76038 | |
| 121 | Institut Curie | Saint-Cloud | France | 92210 | |
| 122 | Institut Gustave Roussy | Villejuif Cedex | France | 94805 | |
| 123 | Local Institution - 451 | Villejuif CEDEX | France | 94805 | |
| 124 | Local Institution - 400 | Dresden | Saxony | Germany | 01307 |
| 125 | Charite - Universitätsmedizin Berlin | Berlin | Germany | 12203 | |
| 126 | Universitaetsklinikum Bonn | Bonn | Germany | 53127 | |
| 127 | Universitaetsklinikum Carl Gustav Carus | Dresden | Germany | 01307 | |
| 128 | University Duesseldorf | Düsseldorf | Germany | 40225 | |
| 129 | Universitaetsklinikum Erlangen | Erlangen | Germany | 91054 | |
| 130 | Staedtische Kliniken Frankfurt am Main Hochst | Frankfurt am Main | Germany | 65929 | |
| 131 | Wilhelm-Anton-Hospital Goch gGmbH Hämatologie und Internistische Onkologie | Goch | Germany | 47574 | |
| 132 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
| 133 | SLK Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen | Heilbronn | Germany | 74078 | |
| 134 | Universitatsklinikum Jena | Jena | Germany | 07740 | |
| 135 | Universitatsklinikum Schleswig-Holstein | Keil | Germany | 24105 | |
| 136 | Universitaetsklinikum Mannheim | Mannheim | Germany | 68167 | |
| 137 | Staedtisches Klinikum Muenchen Schwabing | Muenchen | Germany | 80804 | |
| 138 | TU München - Klinikum rechts der Isar | München | Germany | 81675 | |
| 139 | Klinikum Oldenburg gGmbH | Oldenburg | Germany | 26133 | |
| 140 | St. Antonius-Hospital | Schweiler | Germany | 52249 | |
| 141 | University of Ulm | Ulm | Germany | 89081 | |
| 142 | Tallaght Adelaide and Meath Hospital | Dublin | Ireland | 24 | |
| 143 | University College Hospital Galway | Galway | Ireland | ST46QG | |
| 144 | Soroka University Medical Center | Beer Sheva | Israel | 84101 | |
| 145 | Rambam Medical Center | Haifa | Israel | 35254 | |
| 146 | Hadassah Medical Center | Jerusalem | Israel | 91120 | |
| 147 | Rabin Medical Center | Petach Tikva | Israel | 49100 | |
| 148 | Az. Osp. SS.Antonio e Biagio - SC Ematologia | Alessandria | Italy | 15121 | |
| 149 | Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari | Bari | Italy | 70124 | |
| 150 | Policlinico Sant'Orsola-Malpighi | Bologna | Italy | 40138 | |
| 151 | Ospedale Bingaghi | Cagliari | Italy | O9126 | |
| 152 | Istituti Ospitalieri di Cremona | Cremona | Italy | 26100 | |
| 153 | Azienda Ospedaliero Universitaria Careggi | Firenze | Italy | 50129 | |
| 154 | IRCCS AziendaOspedaliera Universitaria San Martino | Genova | Italy | 16132 | |
| 155 | Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce | Lecce | Italy | 73100 | |
| 156 | Local Institution - 716 | Lecce | Italy | 73100 | |
| 157 | ASST Grande Ospedale Metropolitano Niguarda, Milano | Milano | Italy | 20162 | |
| 158 | Fondazione Ca Granda IRCCS Ospedale Maggiore | Milan | Italy | 20122 | |
| 159 | Ospedale S. Gerardo di Monza | Monza | Italy | 20900 | |
| 160 | Azienda ospedeliera della 2 Universita di Napoli | Naples | Italy | 80131 | |
| 161 | Ospedale Cardarelli | Naples | Italy | 80131 | |
| 162 | AOU San Luigi Gonzaga | Orbassano (TO) | Italy | 10043 | |
| 163 | Local Institution - 705 | Orbassano (TO) | Italy | 10043 | |
| 164 | Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello | Palermo | Italy | 90146 | |
| 165 | Casa di Cura La Maddalena, Divisione di Ematologia | Palermo | Italy | 90146 | |
| 166 | Azienda Ospedaliera Ospedali Riuniti Marche Nord AORMN | Pesaro | Italy | 31122 | |
| 167 | Azienda Ospedaliera "Bianchi-Melacrino-Morelli" | Reggio Calabria | Italy | 89100 | |
| 168 | Local Institution - 700 | Reggio Calabria | Italy | 89100 | |
| 169 | Universita degli Studi di Roma La Sapienza - Azienda Policlinico Umberto I | Roma | Italy | 00161 | |
| 170 | Policlinico Universitario Agostino Gemelli | Roma | Italy | 00168 | |
| 171 | Azienda Ospedaliera S. Andrea - Università La Sapienza | Roma | Italy | 00189 | |
| 172 | Local Institution - 723 | Roma | Italy | 00189 | |
| 173 | Local Institution - 722 | Rome | Italy | 133 | |
| 174 | University Hospital Tor Vergata | Rome | Italy | 133 | |
| 175 | Azienda Ospedaliera Citta della Salute e della Scienza di Torino | Torino | Italy | 10126 | |
| 176 | Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine | Udine | Italy | 33100 | |
| 177 | A.O. Universitaria Fondazione Macchi | Varese | Italy | 21100 | |
| 178 | Pusan National University Hospital | Busan | Korea, Republic of | 49241 | |
| 179 | Kyungpook National University Hospital | Daegu | Korea, Republic of | 700-721 | |
| 180 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | 120-752 | |
| 181 | Samsung Medical Center | Seoul | Korea, Republic of | 135-710 | |
| 182 | The Catholic University of Korea Seoul - Saint Mary's Hospital | Seoul | Korea, Republic of | 137-701 | |
| 183 | Asan Medical Center | Seoul | Korea, Republic of | 138-736 | |
| 184 | Local Institution - 532 | Seoul | Korea, Republic of | 138-736 | |
| 185 | Klaipeda seaman hospital | Klaipeda | Lithuania | 5809 | |
| 186 | Hospital Angeles Lomas - Consultorio 830 | Huixquilucan de Degollado | Mexico | 52763 | |
| 187 | Instituto Nacional de Cancerología | Mexico | Mexico | 14080 | |
| 188 | Hospital Universitario Eleuterio Gomez | Monterrey | Mexico | 64460 | |
| 189 | Local Institution - 250 | Monterrey | Mexico | 64460 | |
| 190 | Szpital Uniwersytecki nr 2 im dr. Jana Biziela | Bydgoszcz | Poland | 85-168 | |
| 191 | Institute of Internal Diseases University of Medicine | Gdansk | Poland | 80-211 | |
| 192 | Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi | Lodz | Poland | 93-510 | |
| 193 | Institute of Hematology and Transfusion Medicine | Warsaw | Poland | 02-776 | |
| 194 | Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu | Wroclaw | Poland | 50-367 | |
| 195 | Centro Hospital e Universitario de Coimbra | Coimbra | Portugal | 4200-072 | |
| 196 | Local Institution - 841 | Coimbra | Portugal | 4200-072 | |
| 197 | Instituto Portugues de Oncologia de Lisboa | Lisboa | Portugal | 1099-023 | |
| 198 | Local Institution - 840 | Lisboa | Portugal | 1099-023 | |
| 199 | Centro Hospitalar de Lisboa Central - Hospital de Santo António dos Capuchos | Lisboa | Portugal | 1150-314 | |
| 200 | Instituto Portugues de Oncologia do Porto, Francisco Gentil | Porto | Portugal | 4200-072 | |
| 201 | Hospital de Sao Joao | Porto | Portugal | 4200 | |
| 202 | Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin | Moscow | Russian Federation | 125101 | |
| 203 | Nizhniy Novgorod State Medical Academy of Roszdrav | Nizhniy Novgorod | Russian Federation | 603005 | |
| 204 | Local Institution - 972 | Saint Petersburg | Russian Federation | 196022 | |
| 205 | Federal Centre of Heart, Blood and Endocrinology of Rosmed technlologies V.A. Almazov | St Petersburg | Russian Federation | 197341 | |
| 206 | Hospital Universitari Germans Trias i Pujol | Badalona (Barcelona) | Spain | 8916 | |
| 207 | Hospital de la Santa Creu i Sant Pau | Barcelona | Spain | 08025 | |
| 208 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 8035 | |
| 209 | Hospital de San Pedro de Alcantara | Caceres | Spain | 10003 | |
| 210 | Hospital Universitario Reina Sofia | Cordoba | Spain | 14004 | |
| 211 | Complejo Universitario La Coruna | La Coruna | Spain | 15006 | |
| 212 | Hospital Universitario La Princesa | Madrid | Spain | 28006 | |
| 213 | Hospital Universitario Gregorio Maranon | Madrid | Spain | 28007 | |
| 214 | Hospital Clinico San Carlos | Madrid | Spain | 28040 | |
| 215 | Hospital Central de Asturias | Oviedo | Spain | 33006 | |
| 216 | Hospital Son Llatzer | Palma de Mallorca | Spain | 7198 | |
| 217 | Hospital Universitario de Salamanca | Salamanca | Spain | 37007 | |
| 218 | Hospital Virgen del Rocio | Sevilla | Spain | 41013 | |
| 219 | Hospital Universitari i Politecnic La Fe de Valencia | Valencia | Spain | 46026 | |
| 220 | Local Institution - 860 | Valencia | Spain | 46026 | |
| 221 | Taipei Veterans General Hospital | Beitou District, Taipei City | Taiwan | 11217 | |
| 222 | Kaohsiung Chang Gung Memorial Hospital | Niaosong District Kaohsiung City | Taiwan | 83301 | |
| 223 | China Medical University Hospital | Taichung, Northern Dist. | Taiwan | 404 | |
| 224 | National Cheng Kung University Hospital | Tainan, Taiana | Taiwan | 704 | |
| 225 | National Taiwan University Hospital | Taipei, Zhongzheng Dist. | Taiwan | 100 | |
| 226 | Hacettepe Universitesi | Ankara | Turkey | 06100 | |
| 227 | Dr. Abdurrahman Yurtaslan Ankara Onkoloji hospital | Ankara | Turkey | 06200 | |
| 228 | Marmara School of Medicine | Istanbul | Turkey | 34662 | |
| 229 | Ondokuz Mayis University Medical Faculty | Samsun | Turkey | 55139 | |
| 230 | Local Institution - 904 | Nottingham | Nottinghamshire | United Kingdom | NG5 1PB |
| 231 | United Lincolnshire Hospitals NHS Trust | Boston | United Kingdom | PE21 9QS | |
| 232 | Royal Sussex County Hospital | Brighton East Sussex | United Kingdom | BN2 5BE | |
| 233 | Kent and Canterbury Hospital | Canterbury Kent | United Kingdom | CT1 3NG | |
| 234 | University College London Hospitals | London | United Kingdom | NW1 2PG | |
| 235 | Kings College Hospital | London | United Kingdom | SE5 9RS | |
| 236 | Imperial College Hammersmith Hospital | London | United Kingdom | W12 0HS | |
| 237 | Maidstone Hospital | Maidstone Kent | United Kingdom | ME16 9QQ | |
| 238 | Christie NHS Trust Hospital | Manchester | United Kingdom | M20 4BX | |
| 239 | Nottingham City Hospital | Nottingham | United Kingdom | NG5 1PB | |
| 240 | Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust | Romford, Essex | United Kingdom | RM7 0AG |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
More Information
Publications
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01757535
Other Study ID Numbers:
- CC-486-AML-001
- 2012-003457-28
First Posted:
Dec 31, 2012
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Keywords provided by Celgene
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were randomized at 147 investigational sites within Europe: Italy, Germany, Spain, United Kingdom, France, Turkey, Austria, Poland, Portugal, Russian Federation, Belgium, Israel, Czech Republic, Ireland, Lithuania, Finland, the United States, Canada, Mexico, Australia, South Korea, Taiwan, and Brazil. |
|---|---|
| Pre-assignment Detail | Participants were randomized to oral azacitidine or placebo and stratified by: Age (at induction therapy)- 55-64 years versus (VS) ≥ 65 years Prior history of myelodysplatic syndromes or chronic myelomonocytic leukemia Cytogenetic risk (induction therapy): intermediate-risk VS poor-risk Given consolidation therapy after induction- Yes/No |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Period Title: Overall Study | ||
| STARTED | 238 | 234 |
| Received Treatment | 236 | 233 |
| COMPLETED | 45 | 26 |
| NOT COMPLETED | 193 | 208 |
Baseline Characteristics
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care | Total |
|---|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. | Total of all reporting groups |
| Overall Participants | 238 | 234 | 472 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
67.9
(5.72)
|
68.0
(5.62)
|
67.9
(5.66)
|
| Age, Customized (Count of Participants) | |||
| 18 to 64 Years |
66
27.7%
|
68
29.1%
|
134
28.4%
|
| 65 to 84 Years |
171
71.8%
|
166
70.9%
|
337
71.4%
|
| ≥ 85 years |
1
0.4%
|
0
0%
|
1
0.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
120
50.4%
|
107
45.7%
|
227
48.1%
|
| Male |
118
49.6%
|
127
54.3%
|
245
51.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
20
8.4%
|
14
6%
|
34
7.2%
|
| Not Hispanic or Latino |
196
82.4%
|
202
86.3%
|
398
84.3%
|
| Unknown or Not Reported |
22
9.2%
|
18
7.7%
|
40
8.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
216
90.8%
|
197
84.2%
|
413
87.5%
|
| Black or African-American |
2
0.8%
|
6
2.6%
|
8
1.7%
|
| Asian |
6
2.5%
|
20
8.5%
|
26
5.5%
|
| Other |
12
5%
|
11
4.7%
|
23
4.9%
|
| Missing |
2
0.8%
|
0
0%
|
2
0.4%
|
| Initial Acute Myeloid Leukemia (AML) Classification (Count of Participants) | |||
| AML with Recurrent Genetic Abnormalities |
39
16.4%
|
46
19.7%
|
85
18%
|
| AML with Myelodysplasia - Related Changes |
49
20.6%
|
42
17.9%
|
91
19.3%
|
| Therapy-related Myeloid Neoplasms |
2
0.8%
|
0
0%
|
2
0.4%
|
| AML not Otherwise Specified |
148
62.2%
|
145
62%
|
293
62.1%
|
| Missing |
0
0%
|
1
0.4%
|
1
0.2%
|
| Type of Acute Myeloid Leukemia (AML) (Count of Participants) | |||
| Primary (de novo) |
213
89.5%
|
216
92.3%
|
429
90.9%
|
| Secondary |
25
10.5%
|
18
7.7%
|
43
9.1%
|
| Cytogenetic Risk Category at Diagnosis (Count of Participants) | |||
| Intermediate |
203
85.3%
|
203
86.8%
|
406
86%
|
| Poor |
35
14.7%
|
31
13.2%
|
66
14%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||
| Grade 0 |
116
48.7%
|
111
47.4%
|
227
48.1%
|
| Grade 1 |
101
42.4%
|
106
45.3%
|
207
43.9%
|
| Grade 2 |
21
8.8%
|
15
6.4%
|
36
7.6%
|
| Grade 3 |
0
0%
|
2
0.9%
|
2
0.4%
|
Outcome Measures
| Title | Kaplan-Meier (K-M) Estimate for Overall Survival (OS) |
|---|---|
| Description | Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive. |
| Time Frame | Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent to treat (ITT) population includes participants who were randomized, regardless of whether they received treatment or not. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 238 | 234 |
| Median (95% Confidence Interval) [Months] |
24.7
|
14.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio is from a Cox proportional hazards model stratified by age, cytogenetic risk category, and received consolidation therapy or not. | |
| Other Statistical Analysis | The confidence interval (CI) for the difference was derived using Kosorok's method. | |
| Title | Kaplan-Meier Estimate of Relapse Free Survival (RFS) |
|---|---|
| Description | RFS was defined as the time from the date of randomization to the date of documented relapse or death from any cause, whichever occurred first. Participants who were still alive without documented relapse, or who were lost to follow-up or withdrew consent without documented relapse, were censored at the date of their last bone marrow assessment, prior to receiving any other therapy for AML. Documented relapse was defined as the earliest date of the following: ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or at least 2 peripheral blasts ≥ 5% within 30 days. |
| Time Frame | From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 238 | 234 |
| Median (95% Confidence Interval) [Months] |
10.2
|
4.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The hazard ratio is from a Cox proportional hazards model stratified by age, cytogenetic risk category, and received consolidation therapy or not. | |
| Title | Kaplan-Meier Estimate of Time to Relapse |
|---|---|
| Description | Time to relapse was defined as the interval (in months) from the date of randomization to the date of documented relapse. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from complete remission (CR)/ complete remission with incomplete blood count recovery (CRi). Documented relapse was defined as, the earliest date of the following: ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or at least 2 peripheral blasts ≥ 5% within 30 days. |
| Time Frame | Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 238 | 234 |
| Median (95% Confidence Interval) [months] |
10.2
|
4.9
|
| Title | Kaplan-Meier Estimates of Time to Discontinuation From Treatment |
|---|---|
| Description | Time to discontinuation from treatment was assessed and defined as the interval from the date of randomization to the date of discontinuation from study drug. Participants who were receiving treatment at the time of study closure were censored at the date of last visit. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from CR/ CRi. |
| Time Frame | From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 238 | 234 |
| Median (95% Confidence Interval) [months] |
11.4
|
6.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 5.4 | |
| Confidence Interval |
(2-Sided) 95% 3.1 to 7.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
|---|---|
| Description | TEAEs include AEs that started between first dose date and 28 days after the last dose of study drug. A serious adverse event (SAE) is: Death Life-threatening event Inpatient hospitalization or prolongation of existing hospitalization Persistent or significant disability or incapacity Congenital anomaly or birth defect Other important medical event The severity of AEs were assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: Grade 1 (Mild): asymptomatic/mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Grade 4: Life-threatening; urgent intervention indicated. Grade 5: Death due to AE. |
| Time Frame | Day 1 (randomization) to the data cut off date of 15 July 2019; the median treatment duration was 11.6 months (range: 0.5 to 74.3 months) for the oral aza arm and 5.7 months (range: 0.7 to 68.5 months) for the placebo arm. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least 1 dose of study drug. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 236 | 233 |
| ≥ 1 TEAE |
231
97.1%
|
225
96.2%
|
| ≥ 1 TEAE Related to Study Treatment |
212
89.1%
|
120
51.3%
|
| ≥ 1 Serious TEAE |
79
33.2%
|
60
25.6%
|
| ≥ 1 Treatment Related Serious TEAE |
22
9.2%
|
5
2.1%
|
| ≥ 1 Grade 3/4 TEAE |
169
71%
|
147
62.8%
|
| ≥ 1 Treatment Related Grade 3/4 TEAE |
113
47.5%
|
54
23.1%
|
| ≥ 1 TEAE Leading to Death |
9
3.8%
|
4
1.7%
|
| ≥ 1 TEAE Leading to Dose Reduction (Red) |
37
15.5%
|
6
2.6%
|
| ≥ 1 TEAE Leading to Dose Interruption |
102
42.9%
|
40
17.1%
|
| ≥ 1 TEAE Leading to Dose Red and Interruption |
24
10.1%
|
3
1.3%
|
| ≥ 1 TEAE Leading to Study Drug Discontinuation |
31
13%
|
10
4.3%
|
| Title | Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline |
|---|---|
| Description | The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated. |
| Time Frame | Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 219 |
| Change from Baseline (CFB) at Cycle 2 Day 1 |
0.6
(7.38)
|
0.3
(7.40)
|
| CFB at C3 D1 |
0.5
(7.95)
|
1.6
(7.27)
|
| CFB at C4 D1 |
0.8
(8.50)
|
1.3
(7.47)
|
| CFB at C5 D1 |
0.9
(7.88)
|
1.6
(8.22)
|
| CFB at C6 D1 |
0.7
(8.18)
|
1.1
(8.39)
|
| CFB at C7 D1 |
0.4
(8.82)
|
1.8
(8.39)
|
| CFB at C8 D1 |
0.4
(8.11)
|
1.5
(7.98)
|
| CFB at C9 D1 |
0.3
(7.42)
|
0.5
(7.95)
|
| CFB at C10 D1 |
1.0
(7.98)
|
1.6
(7.75)
|
| CFB at C11 D1 |
1.0
(7.19)
|
1.5
(8.46)
|
| CFB at C12 D1 |
0.9
(8.02)
|
1.6
(9.25)
|
| CFB at C13 D1 |
1.3
(7.27)
|
2.9
(8.28)
|
| CFB at C14 D1 |
1.1
(7.19)
|
1.1
(10.12)
|
| CFB at C15 D1 |
1.6
(7.36)
|
2.6
(7.24)
|
| CFB at C16 D1 |
1.9
(6.89)
|
1.5
(8.70)
|
| CFB at C17 D1 |
1.9
(7.03)
|
2.4
(7.44)
|
| CFB at C18 D1 |
1.1
(7.34)
|
2.0
(8.82)
|
| CFB at C19 D1 |
1.7
(8.06)
|
1.8
(8.93)
|
| CFB at C20 D1 |
1.3
(8.05)
|
3.6
(7.84)
|
| CFB at C21 D1 |
1.1
(9.19)
|
2.5
(8.57)
|
| CFB at C22 D1 |
0.6
(8.16)
|
3.2
(8.25)
|
| CFB at C23 D1 |
1.0
(8.22)
|
3.2
(8.37)
|
| CFB at C24 D1 |
0.6
(9.96)
|
2.6
(8.89)
|
| CFB at C25 D1 |
0.5
(7.97)
|
1.3
(9.73)
|
| CFB at C26 D1 |
0.8
(9.76)
|
2.5
(8.81)
|
| CFB at C27 D1 |
0.9
(9.39)
|
2.6
(7.85)
|
| CFB at C28 D1 |
1.0
(8.45)
|
1.6
(8.69)
|
| CFB at C29 D1 |
-0.3
(9.76)
|
2.7
(7.69)
|
| CFB at C30 D1 |
1.3
(7.83)
|
3.1
(8.58)
|
| CFB at C31 D1 |
0.5
(6.69)
|
2.9
(7.07)
|
| CFB at C32 D1 |
0.3
(6.15)
|
2.8
(7.17)
|
| CFB at C33 D1 |
-0.2
(7.10)
|
2.8
(5.99)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | Cycle 2 Day 1 (C2, D1) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.711 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C3, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.132 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C4, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.604 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C5, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.393 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C6 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.733 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C7 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.217 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C8 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.308 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C9 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.868 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C10 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.622 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C11 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.603 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C12 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.553 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C13 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.196 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C14 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.955 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C15 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.416 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C16 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.746 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C17 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.692 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C18 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.518 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C19 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.947 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C20 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.139 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C21 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.421 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C22 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.129 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C23 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.208 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C24 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.326 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C25 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.682 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C26 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.431 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C27 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.380 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C28 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.719 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C29 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.137 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C30 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C31 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.128 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C32 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.120 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C33 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.083 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline |
|---|---|
| Description | The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'. |
| Time Frame | Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 217 |
| Change from Baseline (CFB) at Cycle 2 Day 1 |
0.0017
(0.0859)
|
0.0107
(0.1049)
|
| CFB at C3 D1 |
0.0042
(0.0929)
|
0.0122
(0.1222)
|
| CFB at C4 D1 |
0.0085
(0.0861)
|
0.0230
(0.1024)
|
| CFB at C5 D1 |
0.0049
(0.0902)
|
0.0164
(0.1107)
|
| CFB at C6 D1 |
0.0096
(0.0807)
|
0.0148
(0.1290)
|
| CFB at C7 D1 |
0.0115
(0.0937)
|
0.0217
(0.0886)
|
| CFB at C8 D1 |
-0.0011
(0.1045)
|
0.0259
(0.1205)
|
| CFB at C9 D1 |
-0.0055
(0.1054)
|
0.0245
(0.1291)
|
| CFB at C10 D1 |
0.0112
(0.0939)
|
0.0103
(0.1485)
|
| CFB at C11 D1 |
0.0198
(0.0853)
|
0.0364
(0.1149)
|
| CFB at C12 D1 |
0.0080
(0.0900)
|
0.0276
(0.1189)
|
| CFB at C13 D1 |
0.0210
(0.0833)
|
0.0386
(0.1234)
|
| CFB at C14 D1 |
0.0127
(0.1050)
|
0.0135
(0.1620)
|
| CFB at C15 D1 |
0.0199
(0.0900)
|
0.0307
(0.1254)
|
| CFB at C16 D1 |
0.0161
(0.0883)
|
0.0415
(0.1309)
|
| CFB at C17 D1 |
0.0109
(0.1057)
|
0.0494
(0.1369)
|
| CFB at C18 D1 |
0.0162
(0.0923)
|
0.0359
(0.1468)
|
| CFB at C19 D1 |
0.0125
(0.1002)
|
0.0436
(0.1359)
|
| CFB at C20 D1 |
0.0088
(0.1008)
|
0.0505
(0.1410)
|
| CFB at C21 D1 |
0.0087
(0.1203)
|
0.0566
(0.1388)
|
| CFB at C22 D1 |
0.0086
(0.0943)
|
0.0548
(0.1434)
|
| CFB at C23 D1 |
0.0026
(0.1021)
|
0.0556
(0.1491)
|
| CFB at C24 D1 |
0.0104
(0.1008)
|
0.0506
(0.1570)
|
| CFB at C25 D1 |
0.0039
(0.1003)
|
0.0408
(0.1578)
|
| CFB at C26 D1 |
-0.0017
(0.1101)
|
0.0463
(0.1443)
|
| CFB at C27 D1 |
0.0026
(0.1032)
|
0.0459
(0.1394)
|
| CFB at C28 D1 |
-0.0013
(0.0965)
|
0.0419
(0.1490)
|
| CFB at C29 D1 |
0.0043
(0.1005)
|
0.0299
(0.1520)
|
| CFB at C30 D1 |
0.0135
(0.0854)
|
0.0461
(0.1391)
|
| CFB at C31 D1 |
0.0052
(0.0887)
|
0.0399
(0.1484)
|
| CFB at C32 D1 |
-0.0002
(0.0927)
|
0.0223
(0.0845)
|
| CFB at C33 D1 |
0.0082
(0.0803)
|
0.0243
(0.0695)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | Cycle 2 Day 1 (C2, D1) | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.350 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C3, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.475 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C4, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.155 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C5, D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.312 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C6 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.674 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C7 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.398 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C8 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.063 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C9 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.060 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C10 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.957 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C11 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.245 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | C12 D1 | |
| Statistical Test of Hypothesis | p-Value | 0.205 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C13 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.275 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C14 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.969 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C15 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.546 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C16 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.168 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C17 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.076 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C18 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.348 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C19 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.158 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C20 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.068 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C21 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.057 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C22 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.048 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C23 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C24 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.118 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C25 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.163 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C26 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.078 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C27 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C28 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.096 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C29 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.341 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C30 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.184 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C31 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.194 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C32 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.288 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C33 D1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.407 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the FACIT-Fatigue Scale From Baseline |
|---|---|
| Description | A clinically meaningful improvement or worsening was defined as at least 3 points of improvement or worsening from baseline, respectively, for FACIT-Fatigue. The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated. |
| Time Frame | Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 219 |
| Cycle 2 Day 1 (C2, D1) Improvement |
32.0
13.4%
|
35.6
15.2%
|
| C2, D1 No Change |
38.5
16.2%
|
40.0
17.1%
|
| C2, D1 Worsening |
29.5
12.4%
|
24.4
10.4%
|
| C3, D1 Improvement |
36.3
15.3%
|
35.5
15.2%
|
| C3, D1 No Change |
39.5
16.6%
|
44.3
18.9%
|
| C3, D1 Worsening |
24.2
10.2%
|
20.2
8.6%
|
| C4, D1 Improvement |
36.8
15.5%
|
39.4
16.8%
|
| C4, D1 No Change |
36.2
15.2%
|
35.6
15.2%
|
| C4, D1 Worsening |
27.0
11.3%
|
25.0
10.7%
|
| C5, D1 Improvement |
35.2
14.8%
|
47.2
20.2%
|
| C5, D1 No Change |
36.4
15.3%
|
30.6
13.1%
|
| C5, D1 Worsening |
28.4
11.9%
|
22.2
9.5%
|
| C6, D1 Improvement |
37.7
15.8%
|
38.3
16.4%
|
| C6, D1 No Change |
34.1
14.3%
|
35.2
15%
|
| C6, D1 Worsening |
28.1
11.8%
|
26.6
11.4%
|
| C7, D1 Improvement |
36.2
15.2%
|
41.8
17.9%
|
| C7, D1 No Change |
36.2
15.2%
|
30.6
13.1%
|
| C7, D1 Worsening |
27.6
11.6%
|
27.6
11.8%
|
| C8, D1 Improvement |
39.0
16.4%
|
36.0
15.4%
|
| C8, D1 No Change |
32.9
13.8%
|
40.0
17.1%
|
| C8, D1 Worsening |
28.1
11.8%
|
24.0
10.3%
|
| C9, D1 Improvement |
38.8
16.3%
|
35.6
15.2%
|
| C9, D1 No Change |
34.5
14.5%
|
33.3
14.2%
|
| C9, D1 Worsening |
26.6
11.2%
|
31.0
13.2%
|
| C10, D1 Improvement |
41.5
17.4%
|
41.0
17.5%
|
| C10, D1 No Change |
31.5
13.2%
|
33.3
14.2%
|
| C10, D1 Worsening |
26.9
11.3%
|
25.6
10.9%
|
| C11, D1 Improvement |
36.0
15.1%
|
38.5
16.5%
|
| C11, D1 No Change |
33.6
14.1%
|
35.9
15.3%
|
| C11, D1 Worsening |
30.4
12.8%
|
25.6
10.9%
|
| C12, D1 Improvement |
39.7
16.7%
|
43.7
18.7%
|
| C12, D1 No change |
32.2
13.5%
|
31.0
13.2%
|
| C12, D1 Worsening |
28.1
11.8%
|
25.4
10.9%
|
| C13, D1 Improvement |
37.6
15.8%
|
50.0
21.4%
|
| C13, D1 No Change |
38.5
16.2%
|
28.3
12.1%
|
| C13, D1 Worsening |
23.9
10%
|
21.7
9.3%
|
| C14, D1 Improvement |
40.2
16.9%
|
40.3
17.2%
|
| C14, D1 No Change |
33.3
14%
|
29.0
12.4%
|
| C14, D1 Worsening |
26.5
11.1%
|
30.6
13.1%
|
| C15 D1 Improvement |
43.8
18.4%
|
49.1
21%
|
| C15, D1 No Change |
35.4
14.9%
|
27.3
11.7%
|
| C15, D1 Worsening |
20.8
8.7%
|
23.6
10.1%
|
| C16 D1 Improvement |
38.0
16%
|
43.1
18.4%
|
| C16, D1 No Change |
45.7
19.2%
|
29.4
12.6%
|
| C16, D1 Worsening |
16.3
6.8%
|
27.5
11.8%
|
| C17 D1 Improvement |
37.2
15.6%
|
42.6
18.2%
|
| C17, D1 No Change |
44.2
18.6%
|
34.0
14.5%
|
| C17, D1 Worsening |
18.6
7.8%
|
23.4
10%
|
| C18 D1 Improvement |
34.5
14.5%
|
43.2
18.5%
|
| C18, D1 No Change |
39.1
16.4%
|
36.4
15.6%
|
| C18, D1 Worsening |
26.4
11.1%
|
20.5
8.8%
|
| C19 D1 Improvement |
40.5
17%
|
43.9
18.8%
|
| C19, D1 No Change |
32.9
13.8%
|
31.7
13.5%
|
| C19, D1 Worsening |
26.6
11.2%
|
24.4
10.4%
|
| C20 D1 Improvement |
40.8
17.1%
|
50.0
21.4%
|
| C20, D1 No Change |
28.9
12.1%
|
22.5
9.6%
|
| C20, D1 Worsening |
30.3
12.7%
|
27.5
11.8%
|
| C21 D1 Improvement |
34.7
14.6%
|
50.0
21.4%
|
| C21, D1 No Change |
42.7
17.9%
|
27.5
11.8%
|
| C21, D1 Worsening |
22.7
9.5%
|
22.5
9.6%
|
| C22 D1 Improvement |
35.3
14.8%
|
52.6
22.5%
|
| C22, D1 No Change |
36.8
15.5%
|
26.3
11.2%
|
| C22, D1 Worsening |
27.9
11.7%
|
21.1
9%
|
| C23 D1 Improvement |
41.7
17.5%
|
48.6
20.8%
|
| C23, D1 No Change |
27.8
11.7%
|
28.6
12.2%
|
| C23, D1 Worsening |
30.6
12.9%
|
22.9
9.8%
|
| C24 D1 Improvement |
40.0
16.8%
|
47.1
20.1%
|
| C24, D1 No Change |
28.6
12%
|
29.4
12.6%
|
| C24, D1 Worsening |
31.4
13.2%
|
23.5
10%
|
| C25 D1 Improvement |
38.2
16.1%
|
41.9
17.9%
|
| C25, D1 No Change |
33.8
14.2%
|
32.3
13.8%
|
| C25, D1 Worsening |
27.9
11.7%
|
25.8
11%
|
| C26 D1 Improvement |
33.8
14.2%
|
46.7
20%
|
| C26, D1 No Change |
43.1
18.1%
|
40.0
17.1%
|
| C26, D1 Worsening |
23.1
9.7%
|
13.3
5.7%
|
| C27 D1 Improvement |
41.9
17.6%
|
50.0
21.4%
|
| C27, D1 No Change |
30.6
12.9%
|
31.3
13.4%
|
| C27, D1 Worsening |
27.4
11.5%
|
18.8
8%
|
| C28 D1 Improvement |
47.5
20%
|
45.2
19.3%
|
| C28, D1 No Change |
27.9
11.7%
|
38.7
16.5%
|
| C28, D1 Worsening |
24.6
10.3%
|
16.1
6.9%
|
| C29 D1 Improvement |
33.9
14.2%
|
51.6
22.1%
|
| C29, D1 No Change |
33.9
14.2%
|
35.5
15.2%
|
| C29, D1 Worsening |
32.2
13.5%
|
12.9
5.5%
|
| C30 D1 Improvement |
39.6
16.6%
|
53.1
22.7%
|
| C30, D1 No Change |
41.5
17.4%
|
21.9
9.4%
|
| C30, D1 Worsening |
18.9
7.9%
|
25.0
10.7%
|
| C31 D1 Improvement |
39.6
16.6%
|
50.0
21.4%
|
| C31, D1 No Change |
37.5
15.8%
|
34.4
14.7%
|
| C31, D1 Worsening |
22.9
9.6%
|
15.6
6.7%
|
| C32 D1 Improvement |
34.7
14.6%
|
65.5
28%
|
| C32, D1 No Change |
42.9
18%
|
10.3
4.4%
|
| C32, D1 Worsening |
22.4
9.4%
|
24.1
10.3%
|
| C33 D1 Improvement |
28.3
11.9%
|
54.2
23.2%
|
| C33, D1 No Change |
45.7
19.2%
|
33.3
14.2%
|
| C33, D1 Worsening |
26.1
11%
|
12.5
5.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | Cycle 2 Day 1 (C2 D1); Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.391 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. . | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.22 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C3 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.506 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. . | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.18 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C4 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.719 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. . | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio, log |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 95% 0.67 to 1.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C5 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.186 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. . | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.83 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 2.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C6 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.637 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 95% 0.67 to 1.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C7 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.913 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 1.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C8 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.481 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. . | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.24 | |
| Confidence Interval |
(2-Sided) 95% 0.68 to 2.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C9 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.575 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 1.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C10 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.860 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 2.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C11 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.433 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% 0.68 to 2.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C12 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.655 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.17 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 2.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C13 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.651 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.20 | |
| Confidence Interval |
(2-Sided) 95% 0.55 to 2.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C14 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.754 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.44 to 1.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C15 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.675 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 1.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C16 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.082 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% 0.21 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C17 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.551 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 1.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C18 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.547 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.31 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 3.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C19 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.815 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 2.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C20 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.651 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.22 | |
| Confidence Interval |
(2-Sided) 95% 0.52 to 2.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C21 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.774 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 2.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C22 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.359 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.58 | |
| Confidence Interval |
(2-Sided) 95% 0.60 to 4.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C23 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.393 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.49 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 3.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C24 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.418 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.46 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 3.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C25 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.637 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 3.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C26 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.279 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.02 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 7.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C27 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.322 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.72 | |
| Confidence Interval |
(2-Sided) 95% 0.58 to 5.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C28 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.256 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.99 | |
| Confidence Interval |
() 95% 0.62 to 6.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C29 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.034 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.73 | |
| Confidence Interval |
(2-Sided) 95% 1.08 to 12.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C30 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.477 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.68 | |
| Confidence Interval |
(2-Sided) 95% 0.23 to 2.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C31 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.358 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.77 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 5.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C32 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.993 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 3.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C33 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.177 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.67 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 11.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the EQ-5D-3L Scale From Baseline |
|---|---|
| Description | The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'. |
| Time Frame | Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 217 |
| Cycle 2 Day 1 (C2, D1) Improvement |
10.6
4.5%
|
12.9
5.5%
|
| C2, D1 No Change |
82.9
34.8%
|
78.7
33.6%
|
| C2, D1 Worsening |
6.5
2.7%
|
8.4
3.6%
|
| C3, D1 Improvement |
12.2
5.1%
|
13.7
5.9%
|
| C3, D1 No Change |
77.8
32.7%
|
79.2
33.8%
|
| C3, D1 Worsening |
10.1
4.2%
|
7.1
3%
|
| C4, D1 Improvement |
12.6
5.3%
|
14.6
6.2%
|
| C4, D1 No Change |
79.8
33.5%
|
78.5
33.5%
|
| C4, D1 Worsening |
7.7
3.2%
|
7.0
3%
|
| C5, D1 Improvement |
13.2
5.5%
|
13.4
5.7%
|
| C5, D1 No Change |
77.6
32.6%
|
77.5
33.1%
|
| C5, D1 Worsening |
9.2
3.9%
|
9.2
3.9%
|
| C6, D1 Improvement |
11.5
4.8%
|
15.9
6.8%
|
| C6, D1 No Change |
81.8
34.4%
|
76.2
32.6%
|
| C6, D1 Worsening |
6.7
2.8%
|
7.9
3.4%
|
| C7, D1 Improvement |
13.3
5.6%
|
16.7
7.1%
|
| C7, D1 No Change |
77.3
32.5%
|
79.2
33.8%
|
| C7, D1 Worsening |
9.3
3.9%
|
4.2
1.8%
|
| C8, D1 Improvement |
13.1
5.5%
|
18.2
7.8%
|
| C8, D1 No Change |
73.1
30.7%
|
74.4
31.8%
|
| C8, D1 Worsening |
13.8
5.8%
|
7.1
3%
|
| C9, D1 Improvement |
10.9
4.6%
|
15.3
6.5%
|
| C9, D1 No Change |
77.5
32.6%
|
76.5
32.7%
|
| C9, D1 Worsening |
11.6
4.9%
|
8.2
3.5%
|
| C10, D1 Improvement |
16.9
7.1%
|
11.8
5%
|
| C10, D1 No Change |
72.3
30.4%
|
80.3
34.3%
|
| C10, D1 Worsening |
10.8
4.5%
|
7.9
3.4%
|
| C11, D1 Improvement |
16.0
6.7%
|
20.0
8.5%
|
| C11, D1 No Change |
76.0
31.9%
|
73.3
31.3%
|
| C11, D1 Worsening |
8.0
3.4%
|
6.7
2.9%
|
| C12, D1 Improvement |
14.9
6.3%
|
13.2
5.6%
|
| C12, D1 No change |
75.2
31.6%
|
82.4
35.2%
|
| C12, D1 Worsening |
9.9
4.2%
|
4.4
1.9%
|
| C13, D1 Improvement |
17.6
7.4%
|
15.3
6.5%
|
| C13, D1 No Change |
76.9
32.3%
|
78.0
33.3%
|
| C13, D1 Worsening |
5.6
2.4%
|
6.8
2.9%
|
| C14, D1 Improvement |
16.8
7.1%
|
14.8
6.3%
|
| C14, D1 No Change |
73.3
30.8%
|
75.4
32.2%
|
| C14, D1 Worsening |
9.9
4.2%
|
9.8
4.2%
|
| C15 D1 Improvement |
18.8
7.9%
|
14.8
6.3%
|
| C15, D1 No Change |
72.9
30.6%
|
83.3
35.6%
|
| C15, D1 Worsening |
8.3
3.5%
|
1.9
0.8%
|
| C16 D1 Improvement |
17.4
7.3%
|
19.6
8.4%
|
| C16, D1 No Change |
76.1
32%
|
76.5
32.7%
|
| C16, D1 Worsening |
6.5
2.7%
|
3.9
1.7%
|
| C17 D1 Improvement |
17.6
7.4%
|
26.1
11.2%
|
| C17, D1 No Change |
72.9
30.6%
|
71.7
30.6%
|
| C17, D1 Worsening |
9.4
3.9%
|
2.2
0.9%
|
| C18 D1 Improvement |
18.4
7.7%
|
20.5
8.8%
|
| C18, D1 No Change |
71.3
30%
|
72.7
31.1%
|
| C18, D1 Worsening |
10.3
4.3%
|
6.8
2.9%
|
| C19 D1 Improvement |
17.7
7.4%
|
14.6
6.2%
|
| C19, D1 No Change |
73.4
30.8%
|
80.5
34.4%
|
| C19, D1 Worsening |
8.9
3.7%
|
4.9
2.1%
|
| C20 D1 Improvement |
19.7
8.3%
|
20.0
8.5%
|
| C20, D1 No Change |
71.1
29.9%
|
75.0
32.1%
|
| C20, D1 Worsening |
9.2
3.9%
|
5.0
2.1%
|
| C21 D1 Improvement |
17.3
7.3%
|
25.0
10.7%
|
| C21, D1 No Change |
74.7
31.4%
|
70.0
29.9%
|
| C21, D1 Worsening |
8.0
3.4%
|
5.0
2.1%
|
| C22 D1 Improvement |
16.2
6.8%
|
26.3
11.2%
|
| C22, D1 No Change |
72.1
30.3%
|
71.1
30.4%
|
| C22, D1 Worsening |
11.8
5%
|
2.6
1.1%
|
| C23 D1 Improvement |
11.1
4.7%
|
22.9
9.8%
|
| C23, D1 No Change |
79.2
33.3%
|
74.3
31.8%
|
| C23, D1 Worsening |
9.7
4.1%
|
2.9
1.2%
|
| C24 D1 Improvement |
15.7
6.6%
|
23.5
10%
|
| C24, D1 No Change |
74.3
31.2%
|
70.6
30.2%
|
| C24, D1 Worsening |
10.0
4.2%
|
5.9
2.5%
|
| C25 D1 Improvement |
16.2
6.8%
|
16.1
6.9%
|
| C25, D1 No Change |
76.5
32.1%
|
77.4
33.1%
|
| C25, D1 Worsening |
7.4
3.1%
|
6.5
2.8%
|
| C26 D1 Improvement |
15.4
6.5%
|
23.3
10%
|
| C26, D1 No Change |
72.3
30.4%
|
70.0
29.9%
|
| C26, D1 Worsening |
12.3
5.2%
|
6.7
2.9%
|
| C27 D1 Improvement |
16.1
6.8%
|
21.9
9.4%
|
| C27, D1 No Change |
71.0
29.8%
|
75.0
32.1%
|
| C27, D1 Worsening |
12.9
5.4%
|
3.1
1.3%
|
| C28 D1 Improvement |
11.5
4.8%
|
22.6
9.7%
|
| C28, D1 No Change |
77.0
32.4%
|
71.0
30.3%
|
| C28, D1 Worsening |
11.5
4.8%
|
6.5
2.8%
|
| C29 D1 Improvement |
16.9
7.1%
|
22.6
9.7%
|
| C29, D1 No Change |
71.2
29.9%
|
71.0
30.3%
|
| C29, D1 Worsening |
11.9
5%
|
6.5
2.8%
|
| C30 D1 Improvement |
15.1
6.3%
|
31.3
13.4%
|
| C30, D1 No Change |
75.5
31.7%
|
56.3
24.1%
|
| C30, D1 Worsening |
9.4
3.9%
|
12.5
5.3%
|
| C31 D1 Improvement |
14.6
6.1%
|
25.0
10.7%
|
| C31, D1 No Change |
72.9
30.6%
|
62.5
26.7%
|
| C31, D1 Worsening |
12.5
5.3%
|
12.5
5.3%
|
| C32 D1 Improvement |
12.2
5.1%
|
13.8
5.9%
|
| C32, D1 No Change |
73.5
30.9%
|
79.3
33.9%
|
| C32, D1 Worsening |
14.3
6%
|
6.9
2.9%
|
| C33 D1 Improvement |
15.2
6.4%
|
12.5
5.3%
|
| C33, D1 No Change |
78.3
32.9%
|
79.2
33.8%
|
| C33, D1 Worsening |
6.5
2.7%
|
8.3
3.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | Cycle 2 Day 1 (C2 D1); Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.487 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.36 to 1.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C3 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.378 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.39 | |
| Confidence Interval |
(2-Sided) 95% 0.66 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C4 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.926 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 2.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C5 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.921 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.48 to 2.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C6 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.563 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.76 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 1.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C7 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.107 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.61 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 8.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C8 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.126 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 5.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C9 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.664 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.25 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 3.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C10 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.583 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.35 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 3.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C11 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.555 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 4.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C12 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.153 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.09 | |
| Confidence Interval |
(2-Sided) 95% 0.61 to 15.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C13 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.882 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.12 | |
| Confidence Interval |
(2-Sided) 95% 0.26 to 4.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C14 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.799 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.16 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 3.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C15 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.093 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.98 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 38.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C16 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.455 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.88 | |
| Confidence Interval |
(2-Sided) 95% 0.36 to 9.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C17 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.126 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.69 | |
| Confidence Interval |
(2-Sided) 95% 0.56 to 39.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C18 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.638 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.40 | |
| Confidence Interval |
(2-Sided) 95% 0.35 to 5.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C19 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.27 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 11.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C20 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.303 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.25 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 10.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C21 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.575 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.58 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 8.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C22 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 5.06 | |
| Confidence Interval |
(2-Sided) 95% 0.60 to 42.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C23 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.185 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.16 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 38.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C24 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.278 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.79 | |
| Confidence Interval |
(2-Sided) 95% 0.43 to 17.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C25 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.920 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) 95% 0.19 to 6.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C26 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.551 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.67 | |
| Confidence Interval |
(2-Sided) 95% 0.32 to 8.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C27 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.176 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 4.25 | |
| Confidence Interval |
(2-Sided) 95% 0.47 to 38.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C28 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.455 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.92 | |
| Confidence Interval |
(2-Sided) 95% 0.35 to 10.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C29 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.416 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C30 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.693 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.16 to 3.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C31 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.755 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.79 | |
| Confidence Interval |
(2-Sided) 95% 0.18 to 3.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C32 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.327 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.34 | |
| Confidence Interval |
(2-Sided) 95% 0.43 to 12.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | C33 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.612 |
| Comments | The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 4.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) |
|---|---|
| Description | Clinically meaningful deterioration was defined as at least 3 points of deterioration from baseline for at least 2 consecutive visits for the FACIT--Fatigue. The FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all to 4 = very much. The scores that range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, subscores were prorated. |
| Time Frame | From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Results are presented for each post-baseline visit with sample size ≥ 25 in both arms. Death was censored at the date of the last HRQoL assessment visit. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 219 |
| Median (95% Confidence Interval) [Weeks] |
41.1
|
49.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5673 |
| Comments | Stratification factors: Age (at induction therapy): 55 to 64 years and ≥ 65 years Prior history of MDS: yes/no Cytogenetic risk (at induction therapy): intermediate-risk/poor-risk Received consolidation therapy following induction: yes/no | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.0882 | |
| Confidence Interval |
(2-Sided) 95% 0.8146 to 1.4538 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale |
|---|---|
| Description | Clinically meaningful deterioration was defined at least 0.10 point of deterioration from baseline for at least 2 consecutive visits for the EQ-5D Health Utility Index. The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The EQ-5D-3L is scored using the UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'. |
| Time Frame | From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Results are presented for each post-baseline visit with sample size ≥ 25 in both arms. Death was censored at the date of the last HRQoL assessment visit. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 225 | 217 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7522 |
| Comments | Stratification factors: Age (at induction therapy): 55 to 64 years and ≥ 65 years Prior history of MDS: yes/no Cytogenetic risk (at induction therapy): intermediate-risk/poor-risk Received consolidation therapy following induction: yes/no | |
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.9345 | |
| Confidence Interval |
(2-Sided) 95% 0.6136 to 1.4231 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year |
|---|---|
| Description | HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective. |
| Time Frame | Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population includes all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 236 | 233 |
| Number (95% Confidence Interval) [Hospitalizations per person-years] |
0.48
|
0.64
|
| Title | Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year |
|---|---|
| Description | HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective. |
| Time Frame | Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population includes all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Oral Azacitidine Plus Best Supportive Care | Placebo Plus Best Supportive Care |
|---|---|---|
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. |
| Measure Participants | 236 | 233 |
| Number (95% Confidence Interval) [Days per person-years] |
7.89
|
13.36
|
Adverse Events
| Time Frame | Day 1 (randomization) to the date of the data cut off date of 15 July 2019; the median treatment duration was 11.6 months (range: 0.5 to 74.3 months) for the oral azacitidine arm and 5.7 months (range: 0.7 to 68.5 months) for the placebo arm. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Note: Mortality data based off Intent-to-Treat population (all participants who are randomized, regardless of whether they received treatment or not). Serious AE and non-serious AE data based off Safety population (all randomized participants who have received at least 1 dose of study drug). | |||
| Arm/Group Title | Oral Azacitidine | Placebo | ||
| Arm/Group Description | Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. | Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. | ||
All Cause Mortality |
||||
| Oral Azacitidine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 158/238 (66.4%) | 171/234 (73.1%) | ||
Serious Adverse Events |
||||
| Oral Azacitidine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 79/236 (33.5%) | 60/233 (25.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/236 (0.8%) | 3/233 (1.3%) | ||
| Disseminated intravascular coagulation | 0/236 (0%) | 1/233 (0.4%) | ||
| Febrile neutropenia | 16/236 (6.8%) | 9/233 (3.9%) | ||
| Lymphadenitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Neutropenia | 2/236 (0.8%) | 0/233 (0%) | ||
| Pancytopenia | 0/236 (0%) | 1/233 (0.4%) | ||
| Thrombocytopenia | 2/236 (0.8%) | 3/233 (1.3%) | ||
| Thrombocytosis | 1/236 (0.4%) | 0/233 (0%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Angina pectoris | 1/236 (0.4%) | 0/233 (0%) | ||
| Angina unstable | 0/236 (0%) | 1/233 (0.4%) | ||
| Aortic valve disease | 1/236 (0.4%) | 0/233 (0%) | ||
| Atrial fibrillation | 3/236 (1.3%) | 0/233 (0%) | ||
| Cardiac failure congestive | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Cardiogenic shock | 1/236 (0.4%) | 0/233 (0%) | ||
| Coronary artery disease | 0/236 (0%) | 1/233 (0.4%) | ||
| Stress cardiomyopathy | 0/236 (0%) | 1/233 (0.4%) | ||
| Congenital, familial and genetic disorders | ||||
| Hydrocele | 1/236 (0.4%) | 0/233 (0%) | ||
| Eye disorders | ||||
| Iridocyclitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Keratitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Ulcerative keratitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/236 (0%) | 1/233 (0.4%) | ||
| Colitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Constipation | 1/236 (0.4%) | 0/233 (0%) | ||
| Crohn's disease | 1/236 (0.4%) | 0/233 (0%) | ||
| Diarrhoea | 3/236 (1.3%) | 0/233 (0%) | ||
| Dysphagia | 1/236 (0.4%) | 0/233 (0%) | ||
| Gastritis | 2/236 (0.8%) | 0/233 (0%) | ||
| Gastroenteritis eosinophilic | 0/236 (0%) | 1/233 (0.4%) | ||
| Gastrointestinal haemorrhage | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Ileus paralytic | 1/236 (0.4%) | 0/233 (0%) | ||
| Inguinal hernia | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Lower gastrointestinal haemorrhage | 0/236 (0%) | 1/233 (0.4%) | ||
| Melaena | 1/236 (0.4%) | 0/233 (0%) | ||
| Nausea | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Neutropenic colitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Pancreatitis acute | 1/236 (0.4%) | 2/233 (0.9%) | ||
| Small intestinal haemorrhage | 1/236 (0.4%) | 0/233 (0%) | ||
| Upper gastrointestinal haemorrhage | 1/236 (0.4%) | 0/233 (0%) | ||
| Vomiting | 2/236 (0.8%) | 0/233 (0%) | ||
| General disorders | ||||
| Asthenia | 0/236 (0%) | 1/233 (0.4%) | ||
| Fatigue | 2/236 (0.8%) | 1/233 (0.4%) | ||
| General physical health deterioration | 0/236 (0%) | 1/233 (0.4%) | ||
| Multiple organ dysfunction syndrome | 1/236 (0.4%) | 2/233 (0.9%) | ||
| Pyrexia | 6/236 (2.5%) | 1/233 (0.4%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 3/236 (1.3%) | 2/233 (0.9%) | ||
| Cholecystitis acute | 0/236 (0%) | 1/233 (0.4%) | ||
| Cholecystitis chronic | 0/236 (0%) | 1/233 (0.4%) | ||
| Cholelithiasis | 0/236 (0%) | 2/233 (0.9%) | ||
| Hyperbilirubinaemia | 1/236 (0.4%) | 0/233 (0%) | ||
| Immune system disorders | ||||
| Allergy to vaccine | 1/236 (0.4%) | 0/233 (0%) | ||
| Infections and infestations | ||||
| Atypical pneumonia | 1/236 (0.4%) | 0/233 (0%) | ||
| Bacteraemia | 1/236 (0.4%) | 0/233 (0%) | ||
| Bacterial infection | 1/236 (0.4%) | 0/233 (0%) | ||
| Bacterial sepsis | 1/236 (0.4%) | 0/233 (0%) | ||
| Cellulitis | 4/236 (1.7%) | 1/233 (0.4%) | ||
| Cholecystitis infective | 1/236 (0.4%) | 0/233 (0%) | ||
| Clostridium difficile infection | 1/236 (0.4%) | 0/233 (0%) | ||
| Cystitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Device related infection | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Device related sepsis | 1/236 (0.4%) | 0/233 (0%) | ||
| Diverticulitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Endophthalmitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Gastroenteritis | 2/236 (0.8%) | 0/233 (0%) | ||
| Gastroenteritis viral | 1/236 (0.4%) | 0/233 (0%) | ||
| Gastrointestinal infection | 0/236 (0%) | 1/233 (0.4%) | ||
| Herpes zoster | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Influenza | 3/236 (1.3%) | 0/233 (0%) | ||
| Klebsiella sepsis | 1/236 (0.4%) | 0/233 (0%) | ||
| Lung abscess | 1/236 (0.4%) | 0/233 (0%) | ||
| Lung infection | 2/236 (0.8%) | 1/233 (0.4%) | ||
| Neutropenic sepsis | 2/236 (0.8%) | 1/233 (0.4%) | ||
| Pneumonia | 9/236 (3.8%) | 7/233 (3%) | ||
| Pneumonia fungal | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Pseudomonas infection | 1/236 (0.4%) | 0/233 (0%) | ||
| Rectal abscess | 1/236 (0.4%) | 0/233 (0%) | ||
| Respiratory tract infection | 0/236 (0%) | 1/233 (0.4%) | ||
| Salmonellosis | 1/236 (0.4%) | 0/233 (0%) | ||
| Sepsis | 4/236 (1.7%) | 5/233 (2.1%) | ||
| Septic shock | 2/236 (0.8%) | 0/233 (0%) | ||
| Staphylococcal infection | 1/236 (0.4%) | 0/233 (0%) | ||
| Staphylococcal sepsis | 1/236 (0.4%) | 0/233 (0%) | ||
| Urinary tract infection | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Urinary tract infection bacterial | 1/236 (0.4%) | 0/233 (0%) | ||
| Urosepsis | 1/236 (0.4%) | 0/233 (0%) | ||
| Wound infection | 1/236 (0.4%) | 0/233 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Cataract traumatic | 0/236 (0%) | 1/233 (0.4%) | ||
| Chemical peritonitis | 1/236 (0.4%) | 0/233 (0%) | ||
| Fall | 1/236 (0.4%) | 0/233 (0%) | ||
| Femoral neck fracture | 1/236 (0.4%) | 0/233 (0%) | ||
| Foot fracture | 0/236 (0%) | 1/233 (0.4%) | ||
| Hip fracture | 1/236 (0.4%) | 0/233 (0%) | ||
| Post-traumatic pain | 1/236 (0.4%) | 0/233 (0%) | ||
| Spinal fracture | 1/236 (0.4%) | 0/233 (0%) | ||
| Subdural haematoma | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Traumatic intracranial haemorrhage | 1/236 (0.4%) | 0/233 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/236 (0.4%) | 0/233 (0%) | ||
| C-reactive protein increased | 1/236 (0.4%) | 0/233 (0%) | ||
| Gamma-glutamyltransferase increased | 1/236 (0.4%) | 0/233 (0%) | ||
| General physical condition abnormal | 0/236 (0%) | 1/233 (0.4%) | ||
| Troponin increased | 0/236 (0%) | 1/233 (0.4%) | ||
| Weight decreased | 1/236 (0.4%) | 0/233 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/236 (0.4%) | 0/233 (0%) | ||
| Dehydration | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Hyperkalaemia | 2/236 (0.8%) | 0/233 (0%) | ||
| Hypocalcaemia | 1/236 (0.4%) | 0/233 (0%) | ||
| Hypokalaemia | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 3/236 (1.3%) | 0/233 (0%) | ||
| Bone pain | 0/236 (0%) | 1/233 (0.4%) | ||
| Intervertebral disc protrusion | 1/236 (0.4%) | 0/233 (0%) | ||
| Joint effusion | 0/236 (0%) | 1/233 (0.4%) | ||
| Myalgia | 0/236 (0%) | 1/233 (0.4%) | ||
| Osteoarthritis | 1/236 (0.4%) | 0/233 (0%) | ||
| Osteoporotic fracture | 1/236 (0.4%) | 0/233 (0%) | ||
| Spinal pain | 0/236 (0%) | 1/233 (0.4%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/236 (0.4%) | 3/233 (1.3%) | ||
| Cholangiocarcinoma | 0/236 (0%) | 1/233 (0.4%) | ||
| Endometrial cancer | 0/236 (0%) | 1/233 (0.4%) | ||
| Gliomatosis cerebri | 0/236 (0%) | 1/233 (0.4%) | ||
| Lung adenocarcinoma | 1/236 (0.4%) | 0/233 (0%) | ||
| Malignant melanoma | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Meningioma | 1/236 (0.4%) | 0/233 (0%) | ||
| Metastases to meninges | 1/236 (0.4%) | 0/233 (0%) | ||
| Prostatic adenoma | 1/236 (0.4%) | 0/233 (0%) | ||
| Squamous cell carcinoma | 0/236 (0%) | 1/233 (0.4%) | ||
| Squamous cell carcinoma of lung | 0/236 (0%) | 1/233 (0.4%) | ||
| Squamous cell carcinoma of skin | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Nervous system disorders | ||||
| Central nervous system inflammation | 0/236 (0%) | 1/233 (0.4%) | ||
| Cerebral haemorrhage | 2/236 (0.8%) | 1/233 (0.4%) | ||
| Cerebral infarction | 0/236 (0%) | 1/233 (0.4%) | ||
| Cerebral ischaemia | 0/236 (0%) | 1/233 (0.4%) | ||
| Haemorrhage intracranial | 1/236 (0.4%) | 0/233 (0%) | ||
| Ischaemic cerebral infarction | 1/236 (0.4%) | 0/233 (0%) | ||
| Syncope | 0/236 (0%) | 1/233 (0.4%) | ||
| Transient ischaemic attack | 1/236 (0.4%) | 0/233 (0%) | ||
| Psychiatric disorders | ||||
| Behaviour disorder | 1/236 (0.4%) | 0/233 (0%) | ||
| Completed suicide | 1/236 (0.4%) | 0/233 (0%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/236 (0.4%) | 0/233 (0%) | ||
| Ureterolithiasis | 0/236 (0%) | 1/233 (0.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/236 (0.4%) | 0/233 (0%) | ||
| Dyspnoea | 2/236 (0.8%) | 0/233 (0%) | ||
| Epistaxis | 0/236 (0%) | 2/233 (0.9%) | ||
| Pneumonia aspiration | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Pneumonitis | 0/236 (0%) | 1/233 (0.4%) | ||
| Pulmonary embolism | 2/236 (0.8%) | 0/233 (0%) | ||
| Pulmonary haemorrhage | 1/236 (0.4%) | 0/233 (0%) | ||
| Respiratory failure | 0/236 (0%) | 1/233 (0.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acute febrile neutrophilic dermatosis | 1/236 (0.4%) | 0/233 (0%) | ||
| Surgical and medical procedures | ||||
| Toe amputation | 0/236 (0%) | 1/233 (0.4%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/236 (0.4%) | 1/233 (0.4%) | ||
| Hypertension | 0/236 (0%) | 1/233 (0.4%) | ||
| Hypotension | 0/236 (0%) | 1/233 (0.4%) | ||
| Peripheral artery stenosis | 0/236 (0%) | 1/233 (0.4%) | ||
| Thrombophlebitis | 0/236 (0%) | 1/233 (0.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Oral Azacitidine | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 230/236 (97.5%) | 212/233 (91%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 49/236 (20.8%) | 42/233 (18%) | ||
| Febrile neutropenia | 14/236 (5.9%) | 10/233 (4.3%) | ||
| Leukopenia | 25/236 (10.6%) | 19/233 (8.2%) | ||
| Neutropenia | 103/236 (43.6%) | 61/233 (26.2%) | ||
| Thrombocytopenia | 80/236 (33.9%) | 62/233 (26.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 31/236 (13.1%) | 15/233 (6.4%) | ||
| Abdominal pain upper | 21/236 (8.9%) | 12/233 (5.2%) | ||
| Constipation | 91/236 (38.6%) | 56/233 (24%) | ||
| Diarrhoea | 118/236 (50%) | 50/233 (21.5%) | ||
| Flatulence | 13/236 (5.5%) | 4/233 (1.7%) | ||
| Nausea | 153/236 (64.8%) | 54/233 (23.2%) | ||
| Stomatitis | 7/236 (3%) | 12/233 (5.2%) | ||
| Vomiting | 141/236 (59.7%) | 23/233 (9.9%) | ||
| General disorders | ||||
| Asthenia | 44/236 (18.6%) | 12/233 (5.2%) | ||
| Fatigue | 70/236 (29.7%) | 44/233 (18.9%) | ||
| Oedema peripheral | 21/236 (8.9%) | 24/233 (10.3%) | ||
| Pyrexia | 36/236 (15.3%) | 43/233 (18.5%) | ||
| Infections and infestations | ||||
| Bronchitis | 14/236 (5.9%) | 9/233 (3.9%) | ||
| Influenza | 16/236 (6.8%) | 7/233 (3%) | ||
| Nasopharyngitis | 18/236 (7.6%) | 16/233 (6.9%) | ||
| Rhinitis | 12/236 (5.1%) | 4/233 (1.7%) | ||
| Upper respiratory tract infection | 31/236 (13.1%) | 32/233 (13.7%) | ||
| Urinary tract infection | 16/236 (6.8%) | 13/233 (5.6%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 30/236 (12.7%) | 15/233 (6.4%) | ||
| Hypokalaemia | 20/236 (8.5%) | 20/233 (8.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 32/236 (13.6%) | 24/233 (10.3%) | ||
| Back pain | 27/236 (11.4%) | 24/233 (10.3%) | ||
| Musculoskeletal pain | 14/236 (5.9%) | 13/233 (5.6%) | ||
| Pain in extremity | 25/236 (10.6%) | 12/233 (5.2%) | ||
| Nervous system disorders | ||||
| Dizziness | 25/236 (10.6%) | 21/233 (9%) | ||
| Headache | 23/236 (9.7%) | 26/233 (11.2%) | ||
| Psychiatric disorders | ||||
| Anxiety | 16/236 (6.8%) | 8/233 (3.4%) | ||
| Insomnia | 22/236 (9.3%) | 23/233 (9.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 29/236 (12.3%) | 39/233 (16.7%) | ||
| Dyspnoea | 13/236 (5.5%) | 14/233 (6%) | ||
| Epistaxis | 15/236 (6.4%) | 17/233 (7.3%) | ||
| Oropharyngeal pain | 14/236 (5.9%) | 19/233 (8.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 12/236 (5.1%) | 14/233 (6%) | ||
| Vascular disorders | ||||
| Hypertension | 18/236 (7.6%) | 16/233 (6.9%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Results Point of Contact
| Name/Title | Anne McClain, Senior Manager, Clinical Trial Disclosure |
|---|---|
| Organization | Celgene Corporation |
| Phone | 888-260-1599 |
| clinicaltrialdisclosure@celgene.com |
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01757535
Other Study ID Numbers:
- CC-486-AML-001
- 2012-003457-28
First Posted:
Dec 31, 2012
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022