Study of Dasatinib vs Imatinib in Patients With Chronic Myeloid Leukemia (CML) Who Did Not Have Favorable Response to Imatinib (DASCERN)

• Time to Major Molecular Response (MMR) [ Time Frame: Up to 10 years ]
  Time to MMR is how fast patients achieve optimal response. It is the time between randomization date and first date that MMR criteria are satisfied.
• Time to Molecular Response (MR)^4.5 [ Time Frame: Up to 10 years ]
  Time to MR^4.5 is how fast patients achieve a deeper response. It is the time between randomization date and first date that MR^4.5 criteria are satisfied.
• Progression Free Survival (PFS) [ Time Frame: Up to 10 years ]
  PFS is how long patients are likely to live without progression of their disease. It is the time from randomization date to progression date or death date, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to 10 years ]
  OS is how long patients are likely to remain alive. It is the time from randomization date to death date.

• Molecular Response over time - Proportion of randomized subjects who achieve MMR, MR4 and MR4.5 at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12, 18, 24, 36, 48 & 60 ]

  MR4 = 4- log reduction in BCR-ABL transcript from the standardized baseline [0.01% International Standard (IS)]

  MR4.5 = 4.5- log reduction in BCR-ABL transcript from the standardized baseline [0.0032% International Standard (IS)]

• Cytogenetic Response over time - proportion of randomized subjects who achieve Complete Cytogenetic Response (CCyR) or major cytogenetic response (MCyR) at each time-point from Day 1 treatment with first line Imatinib [ Time Frame: Months 6, 12 & 18 ]
• Progression Free Survival (PFS) - PFS is defined as the time from randomization date to progression date or death date, whichever occurs first. Subjects who neither progress nor die, will be censored [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ]
• Overall Survival (OS)- OS is defined as the time from randomization date to death date. Subjects who have not died, will be censored on the last date they are known to be alive [ Time Frame: Months 12, 18, 24, 36, 48 & 60 ]
• Time to and duration of Response - Time to MMR is the time between randomization date and first date that MMR criteria are satisfied [ Time Frame: Months 6, 15, 18, 24, 36 and 48 ]
• Time to and duration of Response - Time to MR4.5 is the time between randomization date and first date that MR4.5 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ]
• Time to and duration of Response - Time to MR4 is the time between randomization date and first date that MR4 criteria are satisfied [ Time Frame: Months 6, 12, 15, 18, 24, 36 and 48 ]
• Time to and duration of Response - Time to CCyR is the time between randomization date and first date that CCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ]
• Time to and duration of Response - Time to MCyR is the time between randomization date and first date that MCyR criteria are satisfied [ Time Frame: Months 6, 12 and 18 ]

• Drug: Imatinib
  Other Names:

  • Gleevec
  • Glivec
• Drug: Dasatinib
  Other Name: Sprycel

• Active Comparator: Arm 1: Imatinib (≥400 mg)
  Imatinib ≥400 mg tablets by mouth once daily (QD) or twice daily (BID) up to 60 months
  Intervention: Drug: Imatinib
• Active Comparator: Arm 2: Dasatinib (100 mg)
  Dasatinib 100 mg tablet by mouth QD up to 60 months
  Intervention: Drug: Dasatinib

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

Inclusion Criteria:

• Chronic Phase (CP)-CML Ph+ patients with complete hematologic response (CHR) but with one log BCR-ABL reduction (BCR-ABL level >10% IS) 3 months of imatinib 400mg treatment. (Imatinib transient dose adjustments due to Adverse Event (AEs) are allowed with a maximum of 2 weeks interruption of treatment with imatinib (cumulative) within the 3 month period before randomization). Imatinib monotherapy must have been started within 6 months of CP-CML diagnosis (Ph + /BCR-ABL detection)
• Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment interruption or dose reductions are required to be on treatment with 400 mg imatinib for two weeks immediately prior to randomization to ensure tolerance to imatinib
• Eastern Co-Operative Group (ECOG) performance status = 0 - 2
• Adequate renal function defined as serum creatinine ≤3 times the institutional upper limit of normal (ULN)
• Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the institutional ULN

Exclusion Criteria:

• Previous diagnosis of accelerated phase or blast crisis
• Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study
• Subjects with less than CHR after 3 months of imatinib treatment or lost CHR after initial achievement
• Documented T315I/A, F317L, or V299L mutations (if already available - not required for screening)
• A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy

• ICON Clinical Research
• PPD
• Molecular MD
• MultiPharma
• Q2 solutions
• Donald E. Morisky
• MD Anderson Symptom Inventory (MDASI-CML)
• OBiS, Inc
• Steering Committee