Immunological monitoring and assessment of biomarkers predictive of clinical response to first-line treatment with bosutinib or imatinib in chronic phase chronic myeloid leukemia

1. Molecular diagnosis of CP CML of <= 6 months (from initial diagnosis).
• Diagnosis of CP CML with molecular confirmation by detection of BCR-ABL rearrangement at screening (cytogenetic assessment for Philadelphia chromosome is not required for enrollment); diagnosis of CP CML will be defined as all of the following:
a) <15% blasts in peripheral blood and bone marrow;
b) <30% blasts plus promyelocytes in peripheral blood and bone marrow;
c) <20% basophils in peripheral blood;
d) >=100 x 109/L platelets (>=100,000/mm3);
e) No evidence of extramedullary disease except hepatosplenomegaly; AND
f) No prior diagnosis of AP or BP-CML.
• Philadelphia chromosome status will be identified at screening. Both Ph+ and Ph- patients may be included.
2. Adequate hepatic and renal function defined as:
• AST/ALT <=2.5 x upper limit of normal (ULN) or <=5 x ULN if attributable to liver involvement of leukemia.
• Total bilirubin <=2.0 x ULN (unless associated with Gilbert*s syndrome).
• Creatinine <=1.5 x ULN.
3. Able to take oral tablets.
4. ECOG performance status of 0 or 1.
5. Age >=18 years.
6. Negative serum pregnancy test within 2 weeks of the first dose of study drug if the patient is a woman of childbearing potential. A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Patients and patient's partners of childbearing potential (physically able to have children) and who are sexually active, must agree to use birth control consistently and correctly during the study and for at least 28 days after they have stopped taking the study drug.
7. Ability to provide written informed consent prior to any study related screening procedures being performed.

1. Any prior medical treatment for CML, including TKIs, with the exception of hydroxyurea and/or anagrelide treatment.
2. Any past or current CNS involvement, including leptomeningeal leukemia.
3. Hypersensitivity to the active substance or to any of the following excipients: microcrystalline cellulose (E460), croscarmellose sodium (E468), poloxamer 188, povidone (E1201), magnesium stearate (E470b), polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, Talc (E553b), iron oxide red (E172).
4. Extramedullary disease only.
5. Major surgery or radiotherapy within 14 days of randomization.
6. Concomitant use of or need for medications known to prolong the QT interval.
7. History of clinically significant or uncontrolled cardiac disease
8. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C or evidence of decompensated liver disease or cirrhosis.
9. Recent or ongoing clinically significant GI disorder, e.g. Crohn*s Disease, Ulcerative Colitis, or prior total or partial gastrectomy.
10. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months.
11. Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the QT interval.
12. Current, or recent (within 6 months), participation in other clinical trials.
13. Women who are pregnant, planning to become pregnant during the study or are breastfeeding a child, or men who are planning to father a child during the study.