An open-label, randomized study of dasatinib vs. high-dose (800 mg) imatinib in the treatment of subjects with chronic phase chronic myeloid leukemia who have had a suboptimal response after at least 3 months of therapy with 400 mg imatinib.Revised Protocol 02, incorporating Administrative Letter 01 and Protocol Amendments 02 (Version 1.0, Dated 29-May-2007) & 3 (Version 1.0, Dated 10-Oct-2007).

Conditions: Subjects with Ph+ chronic phase Chronic Myeloid leukemia (CML)

Registration Number: EUCTR2005-005153-22-DK

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 168

Inclusion Criteria

1) Subjects able to provide written informed consent
2) Available for periodic follow up
3) Life expectancy of at least approximately 3 months

Target population
4) Subjects with Ph+ chronic phase CML who achieved only a suboptimal response (defined as a HR which is monotherapy; a CgR which is 400 mg monotherapy; a PCgR after at least 12 months therapy with imatinib 400 mg monotherapy or less than MMolR with CCgR after at least 18 months therapy with imatinib 400 mg monotherapy). Only subjects who started treatment with imatinib 400 mg monotherapy within 6 months of initial CML diagnosis will be eligible.
5) ECOG performance status (PS) score 0 - 2 (See Protocol Appendix 1)
6) 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
7) Adequate renal function defined as: serum creatinine =3 times the institutional ULN.
8) Serum Na, K, Mg and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be repleted to allow for protocol entry.

Age and Sex
9) Men and women, 18 years of age and older
10) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.
11) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

The following subjects are considered to be eligible for the additional 12 months of
treatment:
• Subjects with a MMolR after initial 12 months of treatment on either dasatinib or
800 mg imatinib. Subjects who obtain their first MMolR at month 12, should have
this response confirmed at month 13 in order to be eligible to the second year of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Sex and Reproductive Status
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least one month before and for at least 3 months after completion of study medication.
2) Women who are pregnant or breastfeeding
3) Women with a positive pregnancy test on enrollment or prior to study drug administration.
4) Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication.

Target Disease Exceptions
5) Subjects eligible for immediate autologous or allogeneic stem cell transplantation.
6) Previous diagnosis of accelerated phase or blast crisis CML
7) Subjects who have previously documented T315I mutation.
Screening for mutation is not required for enrollment onto the protocol.
8) Subjects with a MMolR
9) Subjects with no hematologic response
10) Subjects who lost previously documented CHR, PCgR or CCgR

Medical History and Concurrent Diseases
11) A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
12) Uncontrolled or significant cardiovascular disease, including:
a) A myocardial infarction within 6 months
b) Uncontrolled angina within 3 months
c) Congestive heart failure within 3 months
d) Diagnosed or suspected congenital long QT syndrome
e) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe)
f) Prolonged QTc interval > 500 msec on pre-entry ECG according to Fridericia formula
g) Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
h) Heart rate consistently < 50 beats/minute on pre-entry ECG
i) Uncontrolled hypertension
13) History of significant bleeding disorder unrelated to CML, including:
a) Diagnosed congenital bleeding disorders
b) Diagnosed acquired bleeding disorder within one year
c) Clinically significant bleeding from the GI tract within 6 months
14) Concurrent other malignancies other than CML

Physical and Laboratory Test Findings
15) Intolerance to imatinib 400 mg. Intolerance is defined as occurrence of any of the following at any time during treatment
a) Imatinib-related grade 3 or greater non-hematologic toxicity
b) Imatinib-related grade 4 hematologic toxicity lasting more than 7 days
c) Imatinib-related toxicity leading to imatinib discontinuation or disruption in dosing for >4 weeks

Prohibited Therapies and/or Medications
16) Prior treatment with imatinib at a dose > 400 mg
17) Less than 3 months of prior treatment with imatinib
18) Time from initial diagnosis of CML to start of first imatinib dose > 6 months
19) Subjects with prior stem cell transplantation and/or high dose chemotherapy for CML
20) Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
- quinidine, procainamide, disopyramide
- amiodarone, sotalol, ibutilide, dofetilide
- erythromycins, clarithromycin
- chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, zyprasidone
- cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half