A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia (DASISION)

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

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.

Study Overview

• Status: Completed
• Conditions: Myeloid Leukemia, Chronic
• Intervention / Treatment: Drug: Dasatinib; Drug: Imatinib

• Study Type: Interventional
• Enrollment (Actual): 547
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1021
    • Local Institution
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1280
      • Local Institution
    • Capital Federal, Buenos Aires, Argentina, C1114AAN
      • Local Institution
• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Local Institution
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Local Institution
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution
  • Western Australia
    • Perth, Western Australia, Australia, WA 6000
      • Local Institution
• Austria
  • Innsbruck, Austria, 6020
    • Local Institution
  • Wien, Austria, 1090
    • Local Institution
• Belgium
  • Brugge, Belgium, 8000
    • Local Institution
  • Bruxelles, Belgium, 1200
    • Local Institution
• Brazil
  • Rio De Janeiro, Brazil, 20230130
    • Local Institution
  • Sao Paulo, Brazil, 05403
    • Local Institution
  • Sao Paulo, Brazil, 01401
    • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 80060
      • Local Institution
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083
      • Local Institution
    • Jau, Sao Paulo, Brazil, 17210
      • Local Institution
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile
      • Local Institution
• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Local Institution
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Local Institution
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Local Institution
• Colombia
  • Bogota, Colombia
    • Local Institution
  • Bogota
    • Colombia, Bogota, Colombia
      • Local Institution
• Czech Republic
  • Brno, Czech Republic, 625 00
    • Local Institution
  • Hradec Kralove, Czech Republic, 500 05
    • Local Institution
  • Olomouc, Czech Republic, 775 20
    • Local Institution
  • Prague 2, Czech Republic, 128 20
    • Local Institution
• Denmark
  • Aarhus, Denmark, 8000
    • Local Institution
• France
  • Brest Cedex 02, France, 29609
    • Local Institution
  • Lille Cedex, France, 59037
    • Local Institution
  • Limoges, France, 87042
    • Local Institution
  • Montpellier Cedex, France, 34295
    • Local Institution
  • Paris, France, 75015
    • Local Institution
  • Paris Cedex 10, France, 75475
    • Local Institution
  • Pierre Benite Cedex, France, 69495
    • Local Institution
  • Poitiers Cedex, France, 86021
    • Local Institution
  • Rennes, France, 35033
    • Local Institution
  • Strasbourg Cedex, France, 67091
    • Local Institution
  • Toulouse Cedex 09, France, 31059
    • Local Institution
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
  • Cedex 1
    • Nantes, Cedex 1, France, 44093
      • Local Institution
• Germany
  • Berlin, Germany, 13353
    • Local Institution
  • Rostock, Germany, 18055
    • Local Institution
  • Tuebingen, Germany, 72076
    • Local Institution
  • Ulm, Germany, 89081
    • Local Institution
• Greece
  • Thessaloniki, Greece, 57010
    • Local Institution
• Hungary
  • Budapest, Hungary, 1097
    • Local Institution
  • Debrecen, Hungary, 4012
    • Local Institution
• India
  • Ahmedabad, India, 380009
    • Local Institution
  • Cochin, India, 682304
    • Local Institution
  • Mumbai, India, 400012
    • Local Institution
  • Mumbai, India, 400010
    • Local Institution
  • Mumbai, India, 400014
    • Local Institution
  • Trivandrum, India, 695011
    • Local Institution
  • Tamilnadu
    • Vellore, Tamilnadu, India, 632004
      • Local Institution
• Italy
  • Bologna, Italy, 40138
    • Local Institution
  • Catania, Italy, 95124
    • Local Institution
  • Monza (mb), Italy, 20900
    • Local Institution
  • Orbassano (to), Italy, 10043
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Roma, Italy, 00144
    • Local Institution
  • Roma, Italy, 00161
    • Local Institution
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466-8650
      • Local Institution
  • Chiba
    • Kamogawa-shi, Chiba, Japan, 2968602
      • Local Institution
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 814-0180
      • Local Institution
  • Iwate
    • Morioka-shi, Iwate, Japan, 020-8505
      • Local Institution
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 890-0064
      • Local Institution
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
      • Local Institution
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 6028566
      • Local Institution
  • Miyagi
    • Sendai, Miyagi, Japan
      • Local Institution
  • Okayama
    • Okayama-shi, Okayama, Japan, 7008558
      • Local Institution
  • Osaka
    • Osaka-shi, Osaka, Japan, 545-8586
      • Local Institution
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Local Institution
    • Shinagawa-ku, Tokyo, Japan, 1418625
      • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 02990
      • Local Institution
    • Mexico D.f., Distrito Federal, Mexico, 14000
      • Local Institution
    • Mexico, D. F., Distrito Federal, Mexico, 06726
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80230
      • Local Institution
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Local Institution
  • Nijmegen, Netherlands, 6500 HB
    • Local Institution
• Peru
  • Arequipa, Peru
    • Local Institution
  • Lima, Peru, 34
    • Local Institution
  • Lima, Peru, 11
    • Local Institution
• Poland
  • Chorzow, Poland, 41-500
    • Local Institution
  • Krakow, Poland, 31501
    • Local Institution
  • Lodz, Poland, 93-510
    • Local Institution
  • Poznan, Poland, 60869
    • Local Institution
  • Warsaw, Poland, 02776
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 125167
    • Local Institution
  • Rostov-on-don, Russian Federation, 344022
    • Local Institution
  • St.petersburg, Russian Federation, 197022
    • Local Institution
• Singapore
  • Singapore, Singapore, 169865
    • Local Institution
• Spain
  • A Coruna, Spain, 15706
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution
  • Barcelona, Spain, 08003
    • Local Institution
  • Barcelona, Spain, 08907
    • Local Institution
  • Madrid, Spain, 28006
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution
  • Oviedo, Spain, 33006
    • Local Institution
  • Salamanca, Spain, 37007
    • Local Institution
  • Valencia, Spain, 46009
    • Local Institution
• Turkey
  • Ankara, Turkey, 06100
    • Local Institution
  • Kayseri, Turkey, 38039
    • Local Institution
• United States
  • Oregon
    • Portland, Oregon, United States, 97219
      • Molecular Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib	Drug: Dasatinib; Tablets, oral, dasatinib 50-140 mg once daily (QD); Other Names: BMS-354825; Sprycel®
Active Comparator: Imatinib	Drug: Imatinib; Tablets, oral, imatinib 200-800 mg, QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR.	Pretreatment, every 3 months up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR)	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1.	Years 2, 3, 4 and 5
Percentage of Participants With Major Molecular Response (MMR) at Any Time	Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).	Planned total follow-up duration of 5 years
Time to Confirmed Complete Cytogenic Response (cCCyR) Overall	The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants. .	Day 1 to 5 years
Time to Major Molecular Response (MMR) Overall	The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants.	Day 1 to 5 years
Percentage of Participants With Progression-free Survival (PFS)	PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.	Participants were followed-up for at least 5 years
Percentage of Participants With Overall Survival (OS)	OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.	Participants were followed-up for at least 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.	From date of last person, first visit to date of last person, last visit (approximately 8 years)
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results	ULN=upper limit of normal. Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil count: Grade 3 <1000-500/mm^3; Grade 4 <500/mm^3. Hemoglobin: Grade 3 <8.0-6.5 g/dL; Grade 4 <6.5 g/dL. Platelets: Grade 3 <50,000-25,000/mm^3; Grade 4 <25,000/mm^3. ALT/AST: Grade 3 >5.0-20*ULN; Grade 4 >20*ULN. Total bilirubin: Grade 3 >3-10*ULN; Grade 4 >10*ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total bilirubin: 0.0-1.0 mg/dL. Creatinine: Grade 3 >3.0-6.0*ULN; Grade 4 >6.0*ULN. Phosphate: Grade 3 <2.0-1.0 mg/dL; Grade 4 <1.0 mg/dL. Calcium: Grade 3 <7.0-6.0 mg/dL; Grade 4 <6.0 mg/dL. Potassium: Grade 3 <3.0-2.5 mmol/L; Grade 4 <2.5 mmol/L.	From date of last person, first visit to date of last person, last visit (approximately 8 years)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 30, 2007
• First Submitted That Met QC Criteria: May 31, 2007
• First Posted (Estimate): June 1, 2007

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: December 22, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Dasatinib
• Other Study ID Numbers: CA180-056; 2006-005712-27 (EudraCT Number)