Clinical trial NCT01074047: Study of Vidaza Versus Conventional Care Regimens for the Treatment of Acute Myeloid Leukemia (AML)
Official title: A Phase 3, Multicenter, Randomized, Open-Label, Study of Azacitidine (Vidaza®) Versus Conventional Care Regimens for the Treatment of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Cytarabine
Vidaza
azacitidine
Intensive Chemotherapy
Low Dose Cytarabine
Celgene
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2010-02-24
Enrollment: 488
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effect of azacitidine (Vidaza) to conventional care regimens on overall survival in elderly AML patients.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of one of the following

  * Newly diagnosed de novo acute myeloid leukemia (AML)
  * AML secondary to myelodysplastic syndromes (MDS)
  * AML secondary to exposure to leukemogenic therapy or agents with primary malignancy in remission for at least 2 years
* Bone marrow blasts \>30%
* Age ≥ 65 years
* Easter Cooperative Oncology Group (ECOG) 0-2

Exclusion Criteria:

* Previous cytotoxic or biologic treatment for AML (except hydroxyurea)
* Previous treatment with azacitidine, decitabine or cytarabine
* Prior use of targeted therapy agents (e.g., FLT3 inhibitors, other kinase inhibitors)
* AML French American British subtype (FAB M3)
* AML associated with inv(16), t(8;21), t(16;16), t(15:17), or t(9;22) karyotypes
* Prior bone marrow or stem cell transplantation
* Candidate for allogeneic bone marrow or stem cell transplant
* Diagnosis of malignant disease within the previous 12 months (excluding base cell carcinoma, "in-situ" carcinoma of the cervix or breast or other local malignancy excised or irradiated with a high probability of cure)
* Malignant hepatic tumors
* Uncontrolled systemic infection
* Active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C
* Use of any experimental drug or therapy within 28 days prior to Day 1

Primary outcomes:
measure: Kaplan-Meier Estimates for Overall Survival
timeFrame: Day 1 (randomization) to 40 months
Secondary outcomes:
measure: One-year Overall Survival Rate
timeFrame: From Day 1 (randomization) to 40 months
measure: Event-free Survival (EFS)
timeFrame: Day 1 (randomization) to date of treatment failure, progressive disease, relapse after Complete Remission (CR) or Complete remission with incomplete blood count recovery (CRi), death from any cause. Day 1 (randomization) to 40 months
measure: Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
timeFrame: Day 1 of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up. Day 1 (randomization) to 40 months
measure: Percentage of Participants Who Achieved a Morphologic CR + CRi as Determined by the Independent Review Committee (IRC) Based on International Working Group (IWG) Response Criteria for Acute Myeloid Leukemia (AML)
timeFrame: Day 1 (randomization) to 40 months
measure: Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates
timeFrame: Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.
measure: Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.
timeFrame: Day 1 (randomization) to 40 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017
measure: Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
timeFrame: Baseline to Cycle 3; at approximately 3 months
measure: Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
timeFrame: Baseline to Cycle 5, at approximately 5 months
measure: Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
timeFrame: Baseline to Cycle 7, at approximately 7 months
measure: Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
timeFrame: Baseline to Cycle 9, at approximately 9 months
measure: Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
timeFrame: Baseline to End of Study; at approximately 11-12 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
timeFrame: Baseline to Cycle 3, at approximately 3 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
timeFrame: Baseline to Cycle 5, at approximately 5 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
timeFrame: Baseline to Cycle 7, at approximately 7 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
timeFrame: Baseline to Cycle 9, at approximately 9 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
timeFrame: Baseline to end of study, at approximately 11-12 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
timeFrame: Baseline to Cycle 3, at approximately 3 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
timeFrame: Baseline to Cycle 5, at approximately 5 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
timeFrame: Baseline to Cycle 7, at approximately 7 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
timeFrame: Baseline to Cycle 9, at approximately 9 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
timeFrame: Baseline to end of study, at approximately 11-12 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
timeFrame: Baseline to Cycle 3, at approximately 3 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
timeFrame: Baseline to Cycle 5, at approximately 5 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
timeFrame: Baseline to Cycle 7, at approximately 7 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
timeFrame: Baseline to Cycle 9, at approximately 9 months
measure: HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
timeFrame: Baseline to end of study, at approximately 11-12 months
measure: Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations
timeFrame: Day 1 (randomization) to 40 months
measure: Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year
timeFrame: Day 1 (randomization) to 40 months
measure: HRU: Number of Participants Receiving Transfusions
timeFrame: Day 1 (randomization) to 40 months
measure: HRU: Rate of Transfusions Per Patient Year
timeFrame: Day 1 (randomization) to 40 months
measure: Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From the date of informed consent for the Extension Phase through to the date of last dose of study drug + 28 days up to last visit completed 24 July 2016; maximum duration of exposure to Azacitidine was 871 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
state: Upper Austria
city: Wien
country: Austria
facility: Wilhelminenspital, I Medizinische Abt.
state: Vienna
city: Salzburg
country: Austria
facility: Landeskliniken Salzburg Saint Johanns-Spital, III Medizinische Abteilung
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
state: Hainaut
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godinne
state: Namur
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-vlaanderen
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan
state: West-vlaanderen
city: La Louvière
country: Belgium
facility: Centre Hospitalier de Jolimont-Lobbes
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Ottawa
country: Canada
facility: Ottawa Hospital General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal pavilion Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre Coeur de Montréal
state: Quebec
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: Ontario
country: Canada
facility: Princess Margaret Hospital
city: Beijing
country: China
facility: The Third Hospital of Peking University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Jiangsu
country: China
facility: Peoples Hospital of Jiangsu Province
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Changhai Hospital,the Second Military Medical University
city: Sichuan
country: China
facility: West China Hospital,Sichuan University
city: Tianjin
country: China
facility: Tianjin Blood Disease Hospital
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
state: Jihormoravsky Kraj
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc, hemato-onkologicka klinika
state: Olomoucký Kraj
city: Praha 2
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
state: Praha
city: Praha 2
country: Czechia
facility: Ustav hematologie a krevni transfuze
state: Praha
city: Strasbourg
country: France
facility: Centre Hospitalier Régional Universitaire, Hôpital de Hautepierre
state: Alsace
city: Bobigny
country: France
facility: Hospital Avicenne, Service d'hematologie Clinique
state: ILE-DE-France
city: Clamart Cedex
country: France
facility: Hopital Percy Clamart
state: Ile-de-france
city: Paris Cedex 10
country: France
facility: Hôpital Saint Louis
state: Ile-de-france
city: Limoges
country: France
facility: Centre Hopitalier Universitaire Dupuytren
state: Limousin Lorraine
city: Toulouse Cedex 09
country: France
facility: Centre Hospitalier Universitaire de Toulouse
state: Midi-pyrénées
city: Nice Cedex 3
country: France
facility: Centre Hospitalier Universitaire de Nice
state: Nice
city: Angers cedex 09
country: France
facility: CHRU d'Angers
state: Pays de La Loire
city: Nantes Cedex 1
country: France
facility: Centre Hospitalier Universitaire Nantes, Hotel Dieu
state: Pays de La Loire
city: Amiens Cedex 1
country: France
facility: Centre Hospitalier Universitaire d'Amiens, Groupe Hospitalier Sud
state: Picardie
city: Marseille
country: France
facility: Hôpital de la Conception
state: Provence Alpes Cote D'azur
city: Aquitaine
country: France
facility: Centre Hospitalier de la Cote Basque
city: Lyon Cedex 03
country: France
facility: Centre Hospitalier Universitaire de Lyon-Hôpital Edouard Herriot
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
state: Baden-wuerttemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-wuerttemberg
city: Rostock
country: Germany
facility: University of Rostock, Div. of Haematology and Oncology
state: Mecklenburg-vorpommern
city: Düesseldorf
country: Germany
facility: Heinrich-Heine-Universität Düsseldorf
state: Nordrhein-westfalen
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Zentrum fur Tumorforschung und Tumortherapie
state: Nordrhein-Westfallen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thueringen
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
state: Beersheva
city: Beer Yaakov
country: Israel
facility: Assaf Harofeh Medical Centre
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center - Tel Hashomer, Heart Institute
city: Rionero in Vulture
country: Italy
facility: IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture
state: Potenza
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera "San Luigi Gonzaga"
state: Turin
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
city: Ancona
country: Italy
facility: Azienda Ospedaliera Universitaria - Ospedali Riuniti di Ancona
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico di Bari
city: Bologna
country: Italy
facility: Azienda Ospedaliera Sant'Orsola Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi-Melacrino-Morelli
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I di Roma
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Gangnam-gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
facility: Yonsei University Health System
state: Seoul
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Hospital at Guro
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Wroclaw
country: Poland
facility: Katedra i Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
state: Dolnoslaskie
city: Lódz
country: Poland
facility: Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika
state: Lodzkie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Katowice
country: Poland
facility: Samodzielny Publiczny SK im. A. Mieleckiego Slaskiego Uniwersytetu Medycznego w Katowicach
state: Slaskie
city: Ekaterinburg
country: Russian Federation
facility: Central City Hospital # 7
city: Moscow
country: Russian Federation
facility: City Clinical Hospital n.a. S. P. Botkin
city: Nizhniy Novgorod
country: Russian Federation
facility: State Healthcare Institution "Nizhny Novgorod N.A. Semashko Regional Clinical Hospital"
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Academician I.P. Pavlov Medical University
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Dureta
state: Baleares
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Baleares
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Niao-Sung Hsiang
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung
state: Kaohsiung
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital Pei-Tou District
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Celgene Corporation
name: C L Beach, PharmD
role: STUDY_DIRECTOR
References:
citation: Seymour JF, Dohner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. doi: 10.1186/s12885-017-3803-6.
citation: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.