Open-label Trial of Nilotinib in Patients With Advanced (>CP1) Chronic Myeloid Leukemia or Ph+ Acute Lymphatic Leukemia Pre- and Post- Allogeneic Stem Cell Transplantation.
1. Patients with Ph+ advanced CML (>CR1) or Ph+ALL.
2. Hematological, Cytogenetic (Ph+) and/or BCR/ABL positive documented at diagnosis of
CML or Ph+ALL pre- alloSCT.
3. Patients age 18-65 years of age.
4. .Patients must have an HLA compatible donor willing and capable of donating
peripheral blood stem cells (first choice) or bone marrow progenitor cells using
conventional techniques, and blood lymphocytes if indicated (HLA compatible defined
as 5/6 or 6/6 matched related or matched unrelated donor.
5. Adequate end organ function, defined as the following:
total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL , creatinine < 1.5 x ULN
6. Patient must have LVEF>45% prior entry into study.
7. Patient must have QTc <450 msec at study entry.
8. Lung diffusion capacity (DLCO>40% predicted)
9. Female patients of childbearing potential must have negative pregnancy test within 7
days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential. Male and
female patients of reproductive potential must agree to employ an effective barrier
method of birth control throughout the study and for up to 3 months following
discontinuation of study drug.
10. Written, voluntary informed consent.
1. Patients with CML in first chronic phase
2. Patient has received any other investigational agents within 28 days of first day of
study drug dosing, unless the disease is rapidly progressing.
3. ECOG performance status > 2
4. Patient is < 5 years free of another primary malignancy except: if the other primary
malignancy is not currently clinically significant nor requiring active intervention,
or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
situ. Existence of any other malignant disease is not allowed.
5. Impaired cardiac function including any one of the following:
- LVEF < 45% or below the institutional lower limit of the normal range (whichever
is higher) as determined by echocardiogram
- Inability to determine the QT interval on ECG
- Complete left bundle branch block
- Long QT syndrome or a known family history of long QT syndrome.
- Clinically significant resting bradycardia (<50 beats per minute)
- QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and
electrolytes are not within normal ranges, electrolytes should be corrected and
then the patient re-screened for QTc
- Myocardial infarction within 12 months prior to starting study
- Other clinically significant heart disease (e.g. unstable angina, congestive
heart failure or uncontrolled hypertension).
6. Female patients who are pregnant or breast-feeding.
7. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled
diabetes, chronic renal disease, or active uncontrolled infection).
8. Patient has known chronic liver disease (i.e., chronic active hepatitis, and
9. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
10. Patient had a major surgery within 2 weeks prior to study entry.
11. Patient with any significant history of non-compliance to medical regimens or with
inability to grant reliable informed consent.
12. Patients with active CNS disease (patients with history of CNS disease are allowed).
13. Patients with pleural effusion or ascites
14. Patients with a history of pancreatitis.