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

• Time-in 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.

• 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 ]

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.

• 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

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

• Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, Wang J, Ipiña 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. 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, Boqué 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. Epub 2010 Jun 5.

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