Sustained treatment-free period in the course of a disease when symptoms become less severe in BCR-ABL+ chronic myeloid leukemia: a prospective study comparing a drug called Nilotinib versus another called Imatinib with switch to Nilotinib in absence of optimal response.

Prior treatment

• Previous treatment with BCR-ABL inhibitors for more than 30 days.
• Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for more than three months.
• Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina as defined at page 30 in Exclusion Criteria.
• 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

Other illness

• Uncontrolled hypertension
• History of peripheral arterial occlusive disease.
• History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis

Lab values

• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug.
• Poorly controlled diabetes mellitus (defined as HbA1c >8%

Other

• 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
• Patients unable to understand and to comply with study instructions and requirements
• Refusal to give informed consent.
• Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening.

• Patients eligible for inclusion in this study have to meet all of the following criteria: • Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase o Documented chronic phase CML must meet all the following criteria: 1. < 15% blasts in peripheral blood 2. < 30% blasts plus promyelocytes in peripheral blood 3. < 20% basophils in the peripheral blood 4. = 100 x 109/L (= 100,000/mm3) platelets
• Age =18
• ECOG performance status of 0-2
• Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR
• Adequate end organ function as defined by: o 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 o SGOT (AST) and SGPT (ALT) = 3 x ULN o Serum amylase and lipase = 2 x ULN o Alkaline phosphatase = 2.5 x ULN o Serum creatinine < 1.5 x ULN
• Written informed consent prior to any study procedures.