Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission (QUAZAR AML-001)

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Oral Azacitidine; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 472
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, 3084
    • Local Institution - 503
  • Hobart, Australia, 7000
    • Local Institution - 502
  • Liverpool, Australia, 2170
    • Local Institution - 507
  • Melbourne, Australia, 3004
    • Local Institution - 500
  • Perth, Australia, 6000
    • Local Institution - 505
  • Perth, Australia, 6000
    • Local Institution - 512
  • St Leonards, Australia, 2065
    • Local Institution - 506
  • Woolloongabba, Australia, 4102
    • Local Institution - 501
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Local Institution - 510
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Local Institution - 509
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Local Institution - 508
    • Bedford Park, South Australia, Australia, 5042
      • Local Institution - 511
    • Woodville South, South Australia, Australia, 5011
      • Local Institution - 504
• Austria
  • Graz, Austria, 73013
    • Local Institution - 271
  • Salzburg, Austria, 5020
    • Local Institution - 270
  • Vienna, Austria, 1130
    • Local Institution - 274
  • Vienna, Austria, 1190
    • Local Institution - 273
  • Wien, Austria, 1140
    • Local Institution - 272
• Belgium
  • Brugge, Belgium, 8000
    • Local Institution - 300
  • Charleroi, Belgium, 6000
    • Local Institution - 301
  • Mons, Belgium, 7000
    • Local Institution - 302
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Local Institution - 232
  • Sao Paulo, Brazil, 05651-901
    • Local Institution - 230
  • São Paulo, Brazil, 01308-050
    • Local Institution - 234
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Local Institution - 233
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Local Institution - 231
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution - 605
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E OV9
      • Local Institution - 600
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Local Institution - 601
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1B3V6
      • Local Institution - 603
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution - 604
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 607
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Local Institution - 608
    • Montreal, Quebec, Canada, H4J 1C5
      • Local Institution - 602
• Czechia
  • Praha, Czechia, 128 08
    • Local Institution - 321
  • Praha, Czechia, 128 20
    • Local Institution - 322
  • Jihomoravský Kraj
    • Brno, Jihomoravský Kraj, Czechia, 625 00
      • Local Institution - 320
• Finland
  • Helsinki, Finland, 290
    • Local Institution - 361
  • Tampere, Finland, 33521
    • Local Institution - 362
  • Turku, Finland, 20521
    • Local Institution - 360
• France
  • Amiens, France, 80054
    • Local Institution - 456
  • Argenteuil, France, 95100
    • Local Institution - 465
  • Bobigny Cedex, France, 93009
    • Local Institution - 457
  • Boulognes Sur Mer, France, 62200
    • Local Institution - 462
  • Clamart Cedex, France, 92141
    • Local Institution - 460
  • Creteil, France, 94010
    • Local Institution - 452
  • Le Chesnay Cedex, France, 78157
    • Local Institution - 458
  • Lille, France, 59037
    • Local Institution - 453
  • Limoges Cedex, France, 87042
    • Local Institution - 461
  • Lyon cedex, France, 69437
    • Local Institution - 450
  • Paris, France, 75015
    • Local Institution - 463
  • Paris, France, 75475
    • Local Institution - 454
  • Paris Cedex 10, France, 75475
    • Local Institution - 800
  • Pontoise, France, 95301
    • Local Institution - 464
  • Rouen, France, 76038
    • Local Institution - 455
  • Saint-Cloud, France, 92210
    • Local Institution - 459
  • Villejuif CEDEX, France, 94805
    • Local Institution - 451
• Germany
  • Berlin, Germany, 12203
    • Local Institution - 413
  • Bonn, Germany, 53127
    • Local Institution - 410
  • Düsseldorf, Germany, 40225
    • Local Institution - 406
  • Erlangen, Germany, 91054
    • Local Institution - 415
  • Frankfurt am Main, Germany, 65929
    • Local Institution - 404
  • Goch, Germany, 47574
    • Local Institution - 412
  • Hannover, Germany, 30625
    • Local Institution - 405
  • Heilbronn, Germany, 74078
    • Local Institution - 408
  • Jena, Germany, 07740
    • Local Institution - 414
  • Keil, Germany, 24105
    • Local Institution - 403
  • Mannheim, Germany, 68167
    • Local Institution - 402
  • Muenchen, Germany, 80804
    • Local Institution - 409
  • München, Germany, 81675
    • Local Institution - 411
  • Oldenburg, Germany, 26133
    • Local Institution - 407
  • Schweiler, Germany, 52249
    • Local Institution - 416
  • Ulm, Germany, 89081
    • Local Institution - 401
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Local Institution - 400
• Ireland
  • Dublin, Ireland, 24
    • Local Institution - 950
  • Galway, Ireland, ST46QG
    • Local Institution - 951
• Israel
  • Beer Sheva, Israel, 84101
    • Local Institution - 381
  • Haifa, Israel, 35254
    • Local Institution - 380
  • Jerusalem, Israel, 91120
    • Local Institution - 383
  • Petach Tikva, Israel, 49100
    • Local Institution - 382
• Italy
  • Alessandria, Italy, 15121
    • Local Institution - 701
  • Bari, Italy, 70124
    • Local Institution - 721
  • Bologna, Italy, 40138
    • Local Institution - 720
  • Cagliari, Italy, O9126
    • Local Institution - 710
  • Cremona, Italy, 26100
    • Local Institution - 702
  • Firenze, Italy, 50129
    • Local Institution - 708
  • Genova, Italy, 16132
    • Local Institution - 712
  • Lecce, Italy, 73100
    • Local Institution - 716
  • Milan, Italy, 20122
    • Local Institution - 706
  • Milano, Italy, 20162
    • Local Institution - 726
  • Monza, Italy, 20900
    • Local Institution - 704
  • Naples, Italy, 80131
    • Local Institution - 717
  • Naples, Italy, 80131
    • Local Institution - 725
  • Orbassano (TO), Italy, 10043
    • Local Institution - 705
  • Palermo, Italy, 90146
    • Local Institution - 703
  • Palermo, Italy, 90146
    • Local Institution - 719
  • Pesaro, Italy, 31122
    • Local Institution - 724
  • Reggio Calabria, Italy, 89100
    • Local Institution - 700
  • Roma, Italy, 00189
    • Local Institution - 723
  • Roma, Italy, 00168
    • Local Institution - 714
  • Roma, Italy, 00161
    • Local Institution - 709
  • Rome, Italy, 133
    • Local Institution - 722
  • Torino, Italy, 10126
    • Local Institution - 715
  • Torino, Italy, 10126
    • Local Institution - 718
  • Udine, Italy, 33100
    • Local Institution - 711
  • Varese, Italy, 21100
    • Local Institution - 707
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Local Institution - 535
  • Daegu, Korea, Republic of, 700-721
    • Local Institution - 533
  • Seoul, Korea, Republic of, 120-752
    • Local Institution - 536
  • Seoul, Korea, Republic of, 138-736
    • Local Institution - 532
  • Seoul, Korea, Republic of, 135-710
    • Local Institution - 530
  • Seoul, Korea, Republic of, 137-701
    • Local Institution - 531
• Lithuania
  • Klaipeda, Lithuania, 5809
    • Local Institution - 750
• Mexico
  • Huixquilucan de Degollado, Mexico, 52763
    • Local Institution - 252
  • Mexico, Mexico, 14080
    • Local Institution - 251
  • Monterrey, Mexico, 64460
    • Local Institution - 250
• Poland
  • Bydgoszcz, Poland, 85-168
    • Local Institution - 824
  • Gdansk, Poland, 80-211
    • Local Institution - 820
  • Lodz, Poland, 93-510
    • Local Institution - 822
  • Warsaw, Poland, 02-776
    • Local Institution - 821
  • Wroclaw, Poland, 50-367
    • Local Institution - 823
• Portugal
  • Coimbra, Portugal, 4200-072
    • Local Institution - 841
  • Lisboa, Portugal, 1099-023
    • Local Institution - 840
  • Lisboa, Portugal, 1150-314
    • Local Institution - 843
  • Porto, Portugal, 4200-072
    • Local Institution - 842
  • Porto, Portugal, 4200
    • Local Institution - 844
• Russian Federation
  • Moscow, Russian Federation, 125101
    • Local Institution - 971
  • Nizhniy Novgorod, Russian Federation, 603005
    • Local Institution - 970
  • Saint Petersburg, Russian Federation, 196022
    • Local Institution - 972
  • St Petersburg, Russian Federation, 197341
    • Local Institution - 973
• Spain
  • Badalona (Barcelona), Spain, 8916
    • Local Institution - 869
  • Barcelona, Spain, 08025
    • Local Institution - 871
  • Barcelona, Spain, 08035
    • Local Institution - 870
  • Caceres, Spain, 10003
    • Local Institution - 873
  • Cordoba, Spain, 14004
    • Local Institution - 863
  • La Coruna, Spain, 15006
    • Local Institution - 867
  • Madrid, Spain, 28007
    • Local Institution - 866
  • Madrid, Spain, 28006
    • Local Institution - 868
  • Madrid, Spain, 28040
    • Local Institution - 865
  • Oviedo, Spain, 33006
    • Local Institution - 864
  • Salamanca, Spain, 37007
    • Local Institution - 861
  • Sevilla, Spain, 41013
    • Local Institution - 862
  • Valencia, Spain, 46026
    • Local Institution - 860
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07198
      • Local Institution - 872
• Taiwan
  • Beitou District, Taipei City, Taiwan, 11217
    • Local Institution - 599
  • Niaosong District Kaohsiung City, Taiwan, 83301
    • Local Institution - 595
  • Taichung, Northern Dist., Taiwan, 404
    • Local Institution - 596
  • Tainan, Taiana, Taiwan, 704
    • Local Institution - 597
  • Taipei, Zhongzheng Dist., Taiwan, 10002
    • Local Institution - 598
• Turkey
  • Ankara, Turkey, 06100
    • Local Institution - 653
  • Ankara, Turkey, 06200
    • Local Institution - 650
  • Istanbul, Turkey, 34662
    • Local Institution - 651
  • Samsun, Turkey, 55139
    • Local Institution - 652
• United Kingdom
  • Boston, United Kingdom, PE21 9QS
    • Local Institution - 907
  • Brighton East Sussex, United Kingdom, BN2 5BE
    • Local Institution - 903
  • Canterbury Kent, United Kingdom, CT1 3NG
    • Local Institution - 902
  • London, United Kingdom, NW1 2PG
    • Local Institution - 905
  • London, United Kingdom, SE5 9RS
    • Local Institution - 901
  • London, United Kingdom, W12 0HS
    • Local Institution - 908
  • Maidstone, United Kingdom, ME16 9QQ
    • Local Institution - 909
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 900
  • Romford, Essex, United Kingdom, RM7 0AG
    • Local Institution - 906
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Local Institution - 904
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates, P.C.
  • California
    • Burbank, California, United States, 91505
      • Providence St Joseph Medical Center Cancer Center
    • Duarte, California, United States, 91010-301
      • City of Hope
    • Fresno, California, United States, 93701
      • University of California San Francisco Fresno Campus
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Cancer Center
    • Los Angeles, California, United States, 90095-6956
      • Local Institution - 006
    • Orange, California, United States, 92868
      • Local Institution - 050
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218-1210
      • Rocky Mountain Cancer Center
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Local Institution - 010
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Local Institution - 046
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • Local Institution - 044
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
    • Niles, Illinois, United States, 60714
      • Cancer Care and Hematology Specialists of Chicagoland, P.C. - Niles, IL
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
    • Indianapolis, Indiana, United States, 46202-528
      • Local Institution - 013
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Local Institution - 003
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Local Institution - 049
    • Louisville, Kentucky, United States, 40207
      • Local Institution - 058
  • Louisiana
    • New Orleans, Louisiana, United States, 70121-2483
      • Ochsner Medical Center - Jefferson Highway
    • New Orleans, Louisiana, United States, 70112
      • Local Institution - 047
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01655
      • Local Institution - 015
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 037
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Local Institution - 023
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • Local Institution - 057
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute of New Jersey
  • New York
    • Mineola, New York, United States, 11501-3893
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10065
      • Local Institution - 002
    • New York, New York, United States, 10029
      • Local Institution - 009
    • Rochester, New York, United States, 14642
      • Local Institution - 004
    • Valhalla, New York, United States, 10595
      • Local Institution - 014
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Local Institution - 025
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 016
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Peggy and Charles Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest Oncology Hematology
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Pavillion
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 011
    • Nashville, Tennessee, United States, 37232-5505
      • Local Institution - 007
  • Texas
    • Dallas, Texas, United States, 75390-9068
      • Local Institution - 041
    • Fort Sam Houston, Texas, United States, 78234
      • Local Institution - 034
    • Houston, Texas, United States, 77030
      • Local Institution - 001
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas - Loop
    • San Antonio, Texas, United States, 78229
      • Local Institution - 039
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • Local Institution - 035
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Inst
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/ North Star Lodge
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Froedtert Hospital BMT Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male or female participants ≥ 55 years of age
2. Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
3. 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)
4. 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:

1. 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;
2. Participants who have signed the informed consent for the EP of the study;
3. Participants who do not meet any of the criteria for study discontinuation

Key Exclusion Criteria:

1. 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
2. Prior bone marrow or stem cell transplantation
3. Have achieved CR/CRi following therapy with hypomethylating agents
4. Diagnosis of malignant disease within the previous 12 months
5. Proven central nervous system (CNS) leukemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: CC-486; Onureg®
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier (K-M) Estimate for Overall Survival (OS)	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale	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'.	From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
Kaplan-Meier Estimate of Relapse Free Survival (RFS)	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Kaplan-Meier Estimate of Time to Relapse	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Kaplan-Meier Estimates of Time to Discontinuation From Treatment	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline	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'.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year	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.	From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Roboz GJ, Montesinos P, Selleslag D, Wei A, Jang JH, Falantes J, Voso MT, Sayar H, Porkka K, Marlton P, Almeida A, Mohan S, Ravandi F, Garcia-Manero G, Skikne B, Kantarjian H. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. Future Oncol. 2016 Feb;12(3):293-302. doi: 10.2217/fon.15.326. Epub 2016 Jan 19.
• Dohner H, Wei AH, Roboz GJ, Montesinos P, Thol FR, Ravandi F, Dombret H, Porkka K, Sandhu I, Skikne B, See WL, Ugidos M, Risueno A, Chan ET, Thakurta A, Beach CL, Lopes de Menezes D. Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. Blood. 2022 Oct 13;140(15):1674-1685. doi: 10.1182/blood.2022016293.
• Zhu J, Wu Q, Wang J, Niu T. Cost-effectiveness analysis of azacitidine maintenance therapy in patients with acute myeloid leukemia. Expert Rev Hematol. 2022 Apr;15(4):375-382. doi: 10.1080/17474086.2022.2061456. Epub 2022 May 11.
• Roboz GJ, Ravandi F, Wei AH, Dombret H, Thol F, Voso MT, Schuh AC, Porkka K, La Torre I, Skikne B, Zhong J, Beach CL, Risueno A, Menezes DL, Ossenkoppele G, Dohner H. Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status. Blood. 2022 Apr 7;139(14):2145-2155. doi: 10.1182/blood.2021013404.
• Ravandi F, Roboz GJ, Wei AH, Dohner H, Pocock C, Selleslag D, Montesinos P, Sayar H, Musso M, Figuera-Alvarez A, Safah H, Tse W, Sohn SK, Hiwase D, Chevassut T, Pierdomenico F, La Torre I, Skikne B, Bailey R, Zhong J, Beach CL, Dombret H. Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial. J Hematol Oncol. 2021 Aug 28;14(1):133. doi: 10.1186/s13045-021-01142-x.
• Wei AH, Dohner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Cakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Cermak J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. doi: 10.1056/NEJMoa2004444.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2013
• Primary Completion (Actual): July 15, 2019
• Study Completion (Actual): June 18, 2024

Study Registration Dates

• First Submitted: November 21, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimated): December 31, 2012

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; Maintenance therapy; Oral Azacitidine; Best supportive care; Complete remission
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Disease Progression; Pathologic Complete Response; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Azacitidine
• Other Study ID Numbers: CC-486-AML-001; 2012-003457-28 (EudraCT Number)