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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: September 25, 2014
Last verified: September 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

  Show 109 Study Locations
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: September 25, 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:
Abnormal Karyotype
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Philadelphia Chromosome
Bone Marrow Diseases
Chromosome Aberrations
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Translocation, Genetic
Dasatinib
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014