Clinical trial NCT00481247: A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
Official title: An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL®) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myeloid Leukemia, Chronic
Keywords: Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-06-01
Enrollment: 547
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to compare the confirmed complete cytogenetic response of dasatinib with that of imatinib within 12 months after randomization in patients with newly diagnosed chronic-phase Philadelphia positive chronic myeloid leukemia. The safety of this treatment will also be studied.


Eligibility criteria: Key Inclusion Criteria:

* Male or female, aged 18 years and older
* Chronic phase, Philadelphia Chromosome-positive chronic myeloid leukemia (CML)
* Eastern Cooperative Oncology Group Performance Status score of 0-2

Key Exclusion Criteria:

* Pleural Effusion
* Uncontrolled cardiovascular disease
* Significant bleeding disorder unrelated to CML
* Prior treatment with interferon/imatinib/dasatinib/anti-CML systemic treatments except anagrelide/hydroxyurea

Primary outcomes:
measure: Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months
timeFrame: Pretreatment, every 3 months up to 12 months
Secondary outcomes:
measure: Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR)
timeFrame: Years 2, 3, 4 and 5
measure: Percentage of Participants With Major Molecular Response (MMR) at Any Time
timeFrame: Planned total follow-up duration of 5 years
measure: Time to Confirmed Complete Cytogenic Response (cCCyR) Overall
timeFrame: Day 1 to 5 years
measure: Time to Major Molecular Response (MMR) Overall
timeFrame: Day 1 to 5 years
measure: Percentage of Participants With Progression-free Survival (PFS)
timeFrame: Participants were followed-up for at least 5 years
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: Participants were followed-up for at least 5 years
Other outcomes:
measure: Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths
timeFrame: From date of last person, first visit to date of last person, last visit (approximately 8 years)
measure: Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results
timeFrame: From date of last person, first visit to date of last person, last visit (approximately 8 years)
Locations:
city: Portland
country: United States
facility: Molecular Md
state: Oregon
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Waratah
country: Australia
facility: Local Institution
state: New South Wales
city: Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Greenslopes
country: Australia
facility: Local Institution
state: Queensland
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Innsbruck
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Brugge
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Jau
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Santiago
country: Chile
facility: Local Institution
state: Metropolitana
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Fuzhou
country: China
facility: Local Institution
state: Fujian
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Colombia
country: Colombia
facility: Local Institution
state: Bogota
city: Bogota
country: Colombia
facility: Local Institution
city: Brno
country: Czech Republic
facility: Local Institution
city: Hradec Kralove
country: Czech Republic
facility: Local Institution
city: Olomouc
country: Czech Republic
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Aarhus
country: Denmark
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
state: Cedex 1
city: Brest Cedex 02
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Limoges
country: France
facility: Local Institution
city: Montpellier Cedex
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pierre Benite Cedex
country: France
facility: Local Institution
city: Poitiers Cedex
country: France
facility: Local Institution
city: Rennes
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Toulouse Cedex 09
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Rostock
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Ulm
country: Germany
facility: Local Institution
city: Thessaloniki
country: Greece
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Debrecen
country: Hungary
facility: Local Institution
city: Vellore
country: India
facility: Local Institution
state: Tamilnadu
city: Ahmedabad
country: India
facility: Local Institution
city: Cochin
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Trivandrum
country: India
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Catania
country: Italy
facility: Local Institution
city: Monza (mb)
country: Italy
facility: Local Institution
city: Orbassano (to)
country: Italy
facility: Local Institution
city: Pavia
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Nagoya
country: Japan
facility: Local Institution
state: Aichi
city: Kamogawa-shi
country: Japan
facility: Local Institution
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Morioka-shi
country: Japan
facility: Local Institution
state: Iwate
city: Kagoshima-shi
country: Japan
facility: Local Institution
state: Kagoshima
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Local Institution
state: Kyoto
city: Sendai
country: Japan
facility: Local Institution
state: Miyagi
city: Okayama-shi
country: Japan
facility: Local Institution
state: Okayama
city: Osaka-shi
country: Japan
facility: Local Institution
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Mexico D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico, D. F.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Culiacan
country: Mexico
facility: Local Institution
state: Sinaloa
city: Groningen
country: Netherlands
facility: Local Institution
city: Nijmegen
country: Netherlands
facility: Local Institution
city: Arequipa
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Chorzow
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Warsaw
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Rostov-on-don
country: Russian Federation
facility: Local Institution
city: St.petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: A Coruna
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Malaga
country: Spain
facility: Local Institution
city: Oviedo
country: Spain
facility: Local Institution
city: Salamanca
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Ankara
country: Turkey
facility: Local Institution
city: Kayseri
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Glauche I, Kuhn M, Baldow C, Schulze P, Rothe T, Liebscher H, Roy A, Wang X, Roeder I. Quantitative prediction of long-term molecular response in TKI-treated CML - Lessons from an imatinib versus dasatinib comparison. Sci Rep. 2018 Aug 17;8(1):12330. doi: 10.1038/s41598-018-29923-4.
citation: Hughes TP, Saglio G, Quintas-Cardama A, Mauro MJ, Kim DW, Lipton JH, Bradley-Garelik MB, Ukropec J, Hochhaus A. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase. Leukemia. 2015 Sep;29(9):1832-8. doi: 10.1038/leu.2015.168. Epub 2015 Jun 29.
citation: Fujisawa S, Nakamae H, Ogura M, Ishizawa K, Taniwaki M, Utsunomiya A, Matsue K, Takamatsu Y, Usuki K, Tanimoto M, Ishida Y, Akiyama H, Onishi S. Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): Subset analysis of the DASISION trial with 2-year follow-up. Int J Hematol. 2014 Feb;99(2):141-53. doi: 10.1007/s12185-013-1470-1. Epub 2013 Dec 20.
citation: Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boque C, Chuah C, Pavlovsky C, Mayer J, Cortes J, Baccarani M, Kim DW, Bradley-Garelik MB, Mohamed H, Wildgust M, Hochhaus A. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014 Jan 23;123(4):494-500. doi: 10.1182/blood-2013-06-511592. Epub 2013 Dec 5.
citation: Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, Wang J, Ipina JJ, Kim DW, Ogura M, Pavlovsky C, Junghanss C, Milone JH, Nicolini FE, Robak T, Van Droogenbroeck J, Vellenga E, Bradley-Garelik MB, Zhu C, Hochhaus A. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012 Feb 2;119(5):1123-9. doi: 10.1182/blood-2011-08-376087. Epub 2011 Dec 9.
citation: Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boque C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010 Jun 17;362(24):2260-70. doi: 10.1056/NEJMoa1002315. Epub 2010 Jun 5.