Phase II Study Testing the Tolerability and the Efficacy of Bosutinib in Chronic Phase CML Patients

Inclusion Criteria:

* Signed written informed consent
* Male or female patients aged ≥18 years
* ECOG performance status of 0 to 2
* CML in 1st or late chronic phase
* Intolerant or resistant to pretreatment with one of the approved 1st line TKIs (Imatinib, Nilotinib or Dasatinib). Imatinib therapy prior to 2nd generation TKI therapy for a maximum of 6 weeks is allowed.
* Patients must have a serum creatinine of ≤ 2 x ULN, SGOT/SGPT ≤ 3 x ULN, total bilirubin ≤ 2 x ULN (except known Gilbert's syndrome), and Lipase ≤ 1.5 x ULN
* Female patients of childbearing potential must have a negative pregnancy test performed during screening period
* Male and female patients of reproductive potential must currently use a highly effective contraceptive method and be willing to keep on using it throughout the study and for 6 months following discontinuation of study drug.

Exclusion Criteria:

* Hypersensitivity against Bosutinib or other ingredients of the medicinal product
* Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion
* Patients with BCR-ABL negative CML
* Patients having received Imatinib for more than 6 weeks prior to initiation of 2nd generation TKI (either Nilotinib or Dasatinib)
* Patients with known T315I or V299L mutation
* Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4
* History of pancreatitis, inflammatory bowel disease requiring systemic or topical immunosuppressive therapy within the last 12 months
* Impaired cardiac function, including any of the following:

  1. History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG
  2. ST depression of \>1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG
  3. Congenital long QT syndrome
  4. QTc\> 450 msec in the screening ECG
  5. QT-prolonging concomitant medication
  6. History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG
  7. History of or presence of clinically significant resting bradycardia (\< 50 beats per minute)
  8. Myocardial infarction within 6 months prior to inclusion
  9. Unstable angina diagnosed or treated during the past 12 months
  10. Uncontrolled hypertension, history of labile hypertension
* Known HIV and/or active viral hepatitis (hepatitis B or C). Hepatitis B screening will be performed at screening. Patients with history of hepatitis B with negative HBV DNA may be included when using antiviral prophylaxis
* Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
* Treatment with another investigational product during this study or during the last 30 days prior to study start, except treatment with Interferon alpha within the TIGER (CML V) protocol, which must be stopped at least 7 days prior to study entry
* Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study
* Patient must not have any active bacterial, viral or fungal infection at screening
* Patient must not have severe cerebral dysfunction and/or legal incapacity
* Conditions which interfere with the study treatment at the discretion of the investigator
* Women who are pregnant or breast feeding