Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the following criteria:
• •* Early chronic phase disease (\< 6 months from diagnosis)
• •* Philadelphia chromosome-positive disease
• •* BCR-ABL-positive
• •PATIENT CHARACTERISTICS:
• •WHO performance status 0-1
• •ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due to leukemia)
• •Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia)
• •Serum bilirubin = 1.5 times ULN
• •Serum creatinine = 1.5 times ULN
• •Serum amylase = 1.5 times ULN
• •Serum lipase = 1.5 times ULN
• •Normal serum levels of the following or correctable with supplements:
• •* Potassium
• •* Total calcium (corrected for serum albumin)
• •* Magnesium
• •* Phosphorus
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective barrier method contraception during study and for up to 3 months following completion of study treatment
• •No impaired cardiac function, including any of the following:
• •* LVEF \< 45% by MUGA scan or echocardiogram
• •* Uncontrolled congestive heart failure
• •* Uncontrolled hypertension
• •* Uncontrolled angina pectoris
• •* Myocardial infarction within the past 12 months
• •No significant electric heart abnormalities, including any of the following:
• •* History or active ventricular or atrial tachyarrhythmias
• •* Congenital long QT syndrome and/or QTc \> 450 msec on screening ECG
• •No history of acute (within one year) or chronic pancreatitis
• •No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• •No acute or chronic liver or renal disease considered unrelated to leukemia
• •No known diagnosis of HIV infection
• •No other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
• •No other primary malignancy that is currently clinically significant or requires active intervention
• •PRIOR CONCURRENT THERAPY:
• •More than 2 weeks since prior major surgery and recovered
• •More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days
• •More than 4 weeks since prior investigational drug
• •No prior hematopoietic stem cell transplantation
• •No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol, phenprocoumon)
• •No concurrent medications that would prolong the QT interval
• •No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy
• •Prior treatment with hydroxyurea or anagrelide allowed