A Phase IV Study for Nilotinib in Patients With Imatinib-resistant or Intolerant Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) in Chronic or Accelerated Phase.
- Imatinib resistant chronic myelogenous leukemia in chronic phase with cytogenetic
confirmation of Philadelphia chromosome.
- Documented chronic phase CML as defined by:
- < 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
- the patients with no CHR(complete hematologic response) after 3 months
treatment, no minical cytogenetic response(Ph+<65%) after 6 months treatment, no
major cytogenetic response(Ph+<35%) after 12 months treatment.
- Imatinib resistant Philadelphia positive CML-AC will be defined as at lease one
following and no bast crisis before treatment.
- <30% and ≥ 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 without related treatment
- progression of CML-AP with Imatinib treatment, no hematologic response in bone
marrow after at least 4 weeks treatment with imatinib. Progression from AP will
be defined by increased numbers more than 50% of peripheral WBCs, blasts,
basophils and platelets.
- definition of Imatinib intolerance in CML-CP and AP
- the patients who discontined imatinib treatment with any dosage due to Grade 3
or 4 non-hematologic adverse event or Grade 4 hematologic adverse event
sustained for more than 7 days even best complementary therapy.
- WHO performance scale ≤ 2
- provide signed informed consent form
- Cardiac dysfunction : LVEF <45% by echocardiography, using 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 brachycardia (<50 beats per minute),QTc > 450 msec on baseline ECG (using the
QTcF formula), Myocardial infarction within 12 months prior to starting study, Other
clinically significant heart disease (e.g. unstable angina, congestive heart failure
or uncontrolled hypertension).
- Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS
involvement, lumbar puncture not required).
- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or
- History of significant congenital or acquired bleeding disorder unrelated to cancer.
- Treatment with any CSGF within 1 week of Day 1 except Erythropoietin.
- History of non-compliance to medical regimens or inability to grant consent.
- Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol,
- Patients with another primary malignancy except if the other primary malignancy is
neither currently clinically significant or requiring active intervention
- Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g, erythromycin,
ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir,
mibefradil) and the treatment cannot be either discontinued or switched to a
different medication prior to starting study drug. See link for complete list of
these medications: http://medicine.iupui.edu/flockhart/table.htm.. Novartis must be
contacted if a patient needs to be started on any of these drugs during study
- 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
- History of acute pancreatitis within 1 year of study entry or past medical history of
- patients who diagnosed HIV infection.
- patients who has hypersensitivity for nilotinib or its additives
- Patients who are currently receiving treatment with any medications that have the
potential to prolong the QT interval and the treatment cannot be either discontinued
or switched to a different medication prior to starting study drug (Please see
http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a
comprehensive list of agents that prolong the QT interval)
- Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential
without a negative pregnancy test prior to baseline and (d) male or female of
childbearing potential unwilling to use contraceptive precautions throughout the
- Patients with rare genetic disease such as galactose intolerance, moderate lactase
deficiency or glocose-galactose absoption disorder