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

• ClinicalTrials.gov Identifier: NCT00481247
• Recruitment Status: Completed
• First Posted: June 1, 2007
• Results First Posted: March 15, 2011
• Last Update Posted: February 15, 2017
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: May 30, 2007
• First Posted Date: June 1, 2007
• Results First Submitted Date: November 23, 2010
• Results First Posted Date: March 15, 2011
• Last Update Posted Date: February 15, 2017
• Study Start Date: September 2007
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2016)

Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months [ Time Frame: Pretreatment, every 3 months up to 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.

• Original Primary Outcome Measures (submitted: May 31, 2007): Complete Cytogenetic Response (CCyR) [ Time Frame: within 12 months ]

Current Secondary Outcome Measures (submitted: August 8, 2016)

• Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) [ Time Frame: Years 2, 3, 4 and 5 ]
  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.
• Percentage of Participants With Major Molecular Response (MMR) at Any Time [ Time Frame: Planned total follow-up duration of 5 years ]
  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).
• Time to Confirmed Complete Cytogenic Response (cCCyR) Overall [ Time Frame: Day 1 to 5 years ]
  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. .
• Time to Major Molecular Response (MMR) Overall [ Time Frame: Day 1 to 5 years ]
  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.
• Percentage of Participants With Progression-free Survival (PFS) [ Time Frame: Participants were followed-up for at least 5 years ]
  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.
• Percentage of Participants With Overall Survival (OS) [ Time Frame: Participants were followed-up for at least 5 years ]
  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.

Original Secondary Outcome Measures (submitted: May 31, 2007)

• Major Molecular Response(MMR), Major Cytogenetic Response (MCyR) and Complete Hematologic Response (CHR) [ Time Frame: within 12 months ]
• Best overall MMR, CCyR, MCyr, and CHR rate [ Time Frame: throughout the study ]
• Durations of and times to MMR, CCyR, MCyR and CHR [ Time Frame: throughout the study ]
• Progression-free survival & overall survival [ Time Frame: throughout the study ]
• Toxicity profile [ Time Frame: throughout the study ]

Current Other Pre-specified Outcome Measures (submitted: December 22, 2016)

• 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 [ Time Frame: From date of last person, first visit to date of last person, last visit (approximately 8 years) ]
  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 Abnormalities in On-study Laboratory Test Results [ Time Frame: From date of last person, first visit to date of last person, last visit (approximately 8 years) ]
  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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Myeloid Leukemia, Chronic

Intervention

• Drug: Dasatinib
  Tablets, oral, dasatinib 50-140 mg once daily (QD)
  Other Names:

  • Sprycel®
  • BMS-354825
• Drug: Imatinib
  Tablets, oral, imatinib 200-800 mg, QD

Study Arms

• Experimental: Dasatinib
  Intervention: Drug: Dasatinib
• Active Comparator: Imatinib
  Intervention: Drug: Imatinib

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2016): 547
• Original Estimated Enrollment (submitted: May 31, 2007): 518
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Chile, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Russian Federation, Singapore, Spain, Turkey, United States
• Removed Location Countries: Romania

Administrative Information

• NCT Number: NCT00481247
• Other Study ID Numbers: CA180-056; 2006-005712-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Not Provided
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: December 2016