EnestPath CAMN107AIC05 Inclusion criteria Patients eligible for inclusion in this study have to meet all of the following criteria: 1. Male or female patients, aged ≥ 18 years; 2. ECOG performance status of 0-2; 3. Documented confirmed diagnosis of chronic phase Ph+ and/or BCR-ABL+ CML. Documented chronic phase CML must meet all the following criteria: • < 15% blasts in peripheral blood and bone marrow • < 30% blasts plus promyelocytes in peripheral blood and bone marrow • < 20% basophils in the peripheral blood • ≥ 100 x 109/L (≥ 100,000/mm3) platelets 4. Previous first-line treatment with imatinib for a minimum of 2 calendar years; 5. Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR; 6. Patient in CCyR; [A patient with MMR is considered in CCyR. Therefore cytogenetic response assessment has to be done if a patient has less than MMR in the local lab result or in the blood sample that was sent to EUTOS standardized lab at screening visit (patient will be considered screening failure if not in CCyR)] 7. Adequate end organ function as defined by: • Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab). Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert’s disease) grade < 3; • SGOT (AST) and SGPT (ALT) ≤ 3 x ULN; • Serum amylase and lipase ≤ 2 x ULN; • Alkaline phosphatase ≤ 2.5 x ULN; • Serum creatinine < 1.5 x ULN; 8. Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication: • Potassium • Magnesium • Total calcium (corrected for serum albumin) 9. Patients must have normal marrow function as defined below: • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L • with exception of people of North African descent for whom the threshold for absolute neutrophil count will be ≥1.0 x 109/L due to an increase in the marginal pool of neutrophils. • Hemoglobin ≥ 9.0 g/dL • Platelets ≥ 100 x 109/L 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures; 11. Written informed consent must be obtained prior to any screening procedures. EnestPath CAMN107AIC05 Exclusion criteria Patients eligible for this study must not meet any of the following criteria: 1. Achievement of ≥MR4.0 at study entry; 2. Contraindication to excipients in study medication; 3. Previous treatment with BCR-ABL inhibitors other than imatinib; 4. Patients with any history of detectable atypical BCR-ABL transcripts or patients with detectable atypical BCR-ABL transcripts at screening; 5. Previous anticancer agents for CML (including Interferon) other than imatinib except for cytoreduction after CML diagnosis; 6. Patients who are known to be in the chronic phase of CML for the second time after previous progression to AP/BP; 7. Poorly controlled diabetes mellitus (defined as HbA1c >8%); 8. Impaired cardiac function including any one of the following: • LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) • Inability to determine the QT interval on ECG • Complete left bundle branch block • Right bundle branch block plus left anterior or posterior hemiblock • Use of a ventricular-paced pacemaker • Congenital long QT syndrome or a known family history of long QT syndrome • History of or presence of clinically significant ventricular or atrial tachyarrhythmias • Clinically significant resting bradycardia (< 50 beats per minute) • QTc > 450 msec on the average of three serial screening ECGs (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and the patient re-tested • History or clinical signs of myocardial infarction within 12 months of study entry • History of unstable angina within 12 months of study entry • Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension, unstable angina pectoris) 9. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, uncontrolled infection, history of peripheral arterial occlusive disease); 10. History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis; 11. Known presence of significant congenital or acquired bleeding disorder unrelated to cancer; 12. History of other active solid and/or hematologic malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively; EnestPath CAMN107AIC05 13. Patients who have not recovered from prior surgery; 14. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1; 15. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug; 16. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medications may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John’s Wort, and Ginkgo; 17. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug (see http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm for a list of agents that prolong QT interval); 18. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery); 19. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test; 20. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment; • Placement of an intrauterine device (IUD) or intrauterine system (IUS). Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral EnestPath CAMN107AIC05 oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered to be not of childbearing potential; 21. Patients not able to understand and to comply with study instructions and requirements; 22. Refusal to give informed consent.
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