Imatinib Mesylate (Glivec) as Maintenance Therapy After Cytogenetic Response With Nilotinib (AMN107, Tasigna) First Line in Newly Diagnosed Chronic Myelogenous Leukemia
Inclusion Criteria:
1. Newly diagnosed untreated Philadelphia chromosome-positive CML (use of hydroxyurea
for < 3 months is allowed) in chronic phase defined with 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
- No evidence of extramedullary leukemic involvement, with the exception of liver
and spleen
2. Males or females ≥18 years of age
3. WHO Performance Status of ≤ 2
4. Patients must have the following laboratory values:
- Potassium within normal limits or corrected to within normal limits with
supplements prior to the first dose of study medication
- Total calcium (corrected for serum albumin) within normal limits or correctable
with supplements
- Magnesium within normal limits or corrected to within normal limits with
supplements prior to the first dose of study medication
- Phosphorus ≥ lower limit of normal (LLN) or correctable with supplements
- ALT and AST ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if considered due
to tumor
- Alkaline phosphatase ≤ 2.5 x ULN unless considered due to tumor
- Serum bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
- Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN
5. Written signed and dated informed consent prior to any study procedures being
performed
Exclusion Criteria:
1. Cytopathologically confirmed central nervous system (CNS) infiltration (in absence of
suspicion of CNS involvement, lumbar puncture is not required).
2. Impaired cardiac function, including any one of the following:
- Left ventricle ejection fraction (LVEF) <45% or below the institutional lower
limit of the normal range (whichever is higher) as determined by MUGA scan or
echocardiogram
- Complete left bundle branch block
- Use of a cardiac pacemaker
- ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more
contiguous leads
- Congenital long QT syndrome
- History of or presence of significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (<50 beats per minute)
- QTc >450 msec on screening ECG (using the QTcF formula)
- Right bundle branch block plus left anterior hemiblock, bifascicular block
- Myocardial infarction within 12 months prior to starting nilotinib
- Unstable angina diagnosed or treated during the past 12 months
- Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen)
3. Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol) up to day
before study drug administration
4. Acute or chronic liver or renal disease considered unrelated to tumor such as active
Hepatitis A, B, or C.
5. 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
6. Patients who are currently receiving treatment with any of the medications that have
the potential to prolong the QT interval.
7. Patients who have received any investigational drug ≤4 weeks or investigational
cytotoxic agent within 1 week (or who are within 5 half-lives of a previous
investigational cytotoxic agent) prior to starting study drug or who have not
recovered from side effects of such therapy
8. Patients who have received wide field radiotherapy ≤4 weeks or limited field
radiation for palliation <2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy
9. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
who have not recovered from side effects of such therapy
10. Known diagnosis of human deficiency virus (HIV) infection
11. Patient with a history of another malignancy that is currently clinically significant
or currently requires active intervention.
12. Patients who are pregnant or breast feeding, or adults of reproductive potential not
employing an effective method of birth control (women of childbearing potential must
have a negative serum pregnancy test within 48 hrs prior to administration of
nilotinib). Post menopausal women must be amenorrheic for at least 12 months to be
considered of non-childbearing potential. Male and female patients must agree to
employ an effective method of birth control throughout the study and for 3 months
following discontinuation of study drug.
13. Patients unwilling or unable to comply with the protocol