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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00481247
First received: May 30, 2007
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

The purpose of this clinical research study is to compare the rate of confirmed complete cytogenetic response (cCCyR) of dasatinib to imatinib therapy within 12 months after randomization in newly diagnosed chronic phase Philadelphia positive chronic myeloid leukemia (Ph+ CML) patients. The safety of this treatment will also be studied.


Condition Intervention Phase
Myeloid Leukemia, Chronic
Drug: Dasatinib
Drug: Imatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months [ Time Frame: Pre-treatment, every 3 months up to 12 months ] [ Designated as safety issue: No ]
    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 confirmed cytogenetic response (cCCyR)=those in which all measurements up to at least 28 days after the initial response show an equivalent or better complete cytogenetic response.


Secondary Outcome Measures:
  • Time-in Confirmed cCCyR at Any Time [ Time Frame: Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint or investigator's decision ] [ Designated as safety issue: No ]
    Time-in cCCyR at any time was computed for all randomized subjects. For subjects with cCCyR at any time, it is measured from the time measurement criteria are first met for CCyR(provided it is confirmed later) until the date of progression or death. Subjects with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Subjects without cCCyR are considered to have progressed on day 1.

  • Number of Participants With Major Molecular Response (MMR) at Any Time [ Time Frame: Pre-treatment, every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]
    Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction (RQ-PCR). A major molecular response (MMR) is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (i.e., at least 3 log reduction from a standardized baseline value).

  • Time to Confirmed CCyR Overall [ Time Frame: Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint ] [ Designated as safety issue: No ]

    The Time-to cCCyR for participants with cCCyR is defined as the time from the randomization date until criteria are first met for CCyR (provided it is confirmed later). The time-to cCCyR for all randomized subjects censors non-responders who do not progress at their cytogenetic assessments and non-responders who progress at the maximum time of all randomized subjects.

    .


  • Time to MMR Overall [ Time Frame: Every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]
    The Time-to MMR for participants with MMR is defined as the time from randomization date until measurement criteria are first met for MMR. The time-to MMR for all randomized subjects censor non-responders who do not progress at their last molecular assessments and non-responders who progress at the maximum time of all randomized subjects.

  • Percentage of Participants With Progression-free Survival (PFS) at 12 Months [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: No ]
    PFS=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 & 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.

  • Percentage of Participants With Overall Survival (OS) at 12 Months [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: No ]
    Overall survival (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.


Other Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Grade 3/4 AEs, Drug-related Fluid Retention AEs (FRAEs), Drug-related Serious Adverse Events(SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: Yes ]
    Grade 3=Severe, Grade 4=Life-threatening or disabling. 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.

  • Number of Participants With Grade 3/4 On Study Laboratory Abnormalities [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: Yes ]
    Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil: 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. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST): grade 3 >5.0-20 x ULN (upper limit of normal), grade 4 > 20 x ULN. Total Bilirubin: grade 3 > 3-10 x ULN; grade 4 > 10x 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: total 0.0-1.0 mg/dL


Enrollment: 515
Study Start Date: August 2007
Study Completion Date: December 2013
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Dasatinib
Tablets, oral, dasatinib 50-140 mg once daily (QD)
Other Names:
  • Sprycel®
  • BMS-354825
Active Comparator: B Drug: Imatinib
Tablets, oral, imatinib 200-800 mg, QD

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Male & Female ≥18 years
  • Chronic Phase Ph+ CML
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score 0-2

Exclusion Criteria:

  • Pleural Effusion
  • Uncontrolled cardiovascular (CV) disease
  • Significant bleeding disorder unrelated to CML
  • Prior treatment with interferon/imatinib/dasatinib/anti-CML systemic treatments except anagrelide/hydroxyurea
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481247

  Hide Study Locations
Locations
United States, Oregon
Molecular Md
Portland, Oregon, United States, 97219
Argentina
Local Institution
Capital Federal, Buenos Aires, Argentina, 1280
Local Institution
Capital Federal, Buenos Aires, Argentina, C1114AAN
Local Institution
Buenos Aires, Argentina, 1021
Australia, New South Wales
Local Institution
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Local Institution
Brisbane, Queensland, Australia, 4029
Local Institution
Greenslopes, Queensland, Australia, 4120
Australia, Western Australia
Local Institution
Perth, Western Australia, Australia, WA 6000
Austria
Local Institution
Innsbruck, Austria, 6020
Local Institution
Wien, Austria, 1090
Belgium
Local Institution
Brugge, Belgium, 8000
Local Institution
Bruxelles, Belgium, 1200
Brazil
Local Institution
Curitiba, Parana, Brazil, 80060
Local Institution
Campinas, Sao Paulo, Brazil, 13083
Local Institution
Jau, Sao Paulo, Brazil, 17210
Local Institution
Rio De Janeiro, Brazil, 20230130
Local Institution
Sao Paulo, Brazil, 05403
Local Institution
Sao Paulo, Brazil, 01401
Chile
Local Institution
Santiago, Metropolitana, Chile
China, Beijing
Local Institution
Beijing, Beijing, China, 100044
China, Fujian
Local Institution
Fuzhou, Fujian, China, 350001
China, Shanghai
Local Institution
Shanghai, Shanghai, China, 200025
China, Tianjin
Local Institution
Tianjin, Tianjin, China, 300020
Colombia
Local Institution
Colombia, Bogota, Colombia
Local Institution
Bogota, Colombia
Czech Republic
Local Institution
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
Denmark
Local Institution
Aarhus, Denmark, 8000
France
Local Institution
Nantes, Cedex 1, France, 44093
Local Institution
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
Germany
Local Institution
Berlin, Germany, 13353
Local Institution
Rostock, Germany, 18055
Local Institution
Tuebingen, Germany, 72076
Local Institution
Ulm, Germany, 89081
Greece
Local Institution
Thessaloniki, Greece, 57010
Hungary
Local Institution
Budapest, Hungary, 1097
Local Institution
Debrecen, Hungary, 4012
India
Local Institution
Vellore, Tamilnadu, India, 632004
Local Institution
Ahmedabad, India, 380009
Local Institution
Cochin, India, 682304
Local Institution
Mumbai, India, 400014
Local Institution
Mumbai, India, 400012
Local Institution
Mumbai, India, 400010
Local Institution
Trivandrum, India, 695011
Italy
Local Institution
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, 00161
Local Institution
Roma, Italy, 00144
Japan
Local Institution
Nagoya, Aichi, Japan, 466-8650
Local Institution
Kamogawa-shi, Chiba, Japan, 2968602
Local Institution
Fukuoka-shi, Fukuoka, Japan, 814-0180
Local Institution
Morioka-shi, Iwate, Japan, 020-8505
Local Institution
Kagoshima-shi, Kagoshima, Japan, 890-0064
Local Institution
Yokohama, Kanagawa, Japan, 232-0024
Local Institution
Kyoto-shi, Kyoto, Japan, 6028566
Local Institution
Sendai, Miyagi, Japan
Local Institution
Okayama-shi, Okayama, Japan, 7008558
Local Institution
Osaka-shi, Osaka, Japan, 545-8586
Local Institution
Bunkyo-ku, Tokyo, Japan, 113-8677
Local Institution
Shinagawa-ku, Tokyo, Japan, 1418625
Korea, Republic of
Local Institution
Seoul, Korea, Republic of, 137-040
Local Institution
Seoul, Korea, Republic of, 138-736
Mexico
Local Institution
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
Monterrey, Nuevo Leon, Mexico, 64460
Local Institution
Culiacan, Sinaloa, Mexico, 80230
Netherlands
Local Institution
Groningen, Netherlands, 9700 RB
Local Institution
Nijmegen, Netherlands, 6500 HB
Peru
Local Institution
Arequipa, Peru
Local Institution
Lima, Peru, 34
Local Institution
Lima, Peru, 11
Poland
Local Institution
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
Russian Federation
Local Institution
Moscow, Russian Federation, 125167
Local Institution
Rostov-on-don, Russian Federation, 344022
Local Institution
St.petersburg, Russian Federation, 197022
Singapore
Local Institution
Singapore, Singapore, 169865
Spain
Local Institution
A Coruna, Spain, 15706
Local Institution
Barcelona, Spain, 08907
Local Institution
Barcelona, Spain, 08003
Local Institution
Barcelona, Spain, 08036
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
Turkey
Local Institution
Ankara, Turkey, 06100
Local Institution
Kayseri, Turkey, 38039
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00481247     History of Changes
Other Study ID Numbers: CA180-056, 2006-005712-27
Study First Received: May 30, 2007
Results First Received: November 23, 2010
Last Updated: August 5, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
India: Central Drugs Standard Control Organization
Greece: National Organization of Medicines
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Japan: Pharmaceuticals and Medical Devices Agency
Turkey: Ministry of Health
China: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Poland: National Institute of Medicines
Russia: Ministry of Health of the Russian Federation
Austria: Federal Office for Safety in Health Care
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Chile: CONEP
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Peru: Instituto Nacional de Salud
Mexico: Federal Commission for Sanitary Risks Protection
Denmark: Danish Dataprotection Agency
Italy: Ministry of Health
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Bristol-Myers Squibb:
Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Abnormal Karyotype
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Disease Attributes
Imatinib
Dasatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014