Clinical trial NCT00384228 (phase 1/phase 2, status: completed)
Conditions: chronic myelogenous leukemia, acute lymphoblastic leukemia (philadelphia chromosome positive)
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: nilotinib
SMILES: CC1=CN(C=N1)C1=CC(NC(=O)C2=CC=C(C)C(NC3=NC=CC(=N3)C3=CN=CC=C3)=C2)=CC(=C1)C(F)(F)F
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed as Ph+ ALL who are either relapsed after or refractory to standard therapy

          -  Diagnosed as CML in blast crisis or accelerated phase or chronic phase who are
             resistant or intolerant to imatinib

          -  Performance status is normal or ambulatory and capable of all self-care Exclusion
             Criteria

          -  A history of significant or serious uncontrolled cardiovascular disease

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of nilotinib

          -  Patients who are pregnant or breast feeding, or adults of reproductive potential not
             employing an effective method of birth control

        Exclusion Criteria:

          -  Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS
             involvement, lumbar puncture is not required

          -  Impaired cardiac function, including any one of the following

               -  LVEF < 45% as determined by 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 > 480 msec on screening ECG (using the QTcF formula)

               -  Right bundle branch block plus left anterior hemiblock, bifascicular block

               -  Myocardial infarction within 3 months prior to starting AMN107

               -  Uncontrolled angina pectoris

          -  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)

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of AMN107 (e.g. ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

          -  Use of therapeutic warfarin

          -  Acute or chronic liver or renal disease considered unrelated to tumor (e.g.,
             hepatitis, cirrhosis, renal insufficiency, etc.)

          -  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

          -  Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1
             week prior to starting study drug.

          -  Patients who are currently receiving treatment with any of the medications listed in
             (cf. Post-text suppl. 5) that cannot be either discontinued or switched to a different
             medication prior to starting study drug. The medications listed in (cf. Post-text
             suppl. 5) have the potential to prolong the Q-T interval.

          -  Patients who have received chemotherapy ≤ 1 week or who are within 5 half-lives of
             their last dose chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting
             study drug or who have not recovered from side effects of such therapy. Hydroxyurea is
             permitted at the investigator's discretion prior to enrollment.

          -  Patients who have received Glivec® ≤ 1 week or who have not recovered from side
             effects of such therapy.

          -  Patients who have received immunotherapy ≤ 1 week prior to starting study drug or who
             have not recovered from side effects of such therapy.

          -  Patients who have received any investigational drug (excluding STI571/Glivec) ≤ 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.

          -  Patients who have received wide field radiotherapy ≤ 4 week or limited field radiation
             for palliation ≤ 2 week prior to starting study drug or who have not recovered from
             side effects of such therapy.

          -  Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
             who have not recovered from side effects of such therapy.

          -  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 AMN107).
             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
             barrier method of birth control throughout the study and for up to 3 months following
             discontinuation of study drug

          -  Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
             mandatory)

          -  Patients with a history of another primary malignancy that is currently clinically
             significant or currently requires active intervention.

          -  Patients unwilling or unable to comply with the protocol

        Other protocol-defined inclusion and exclusion criteria may apply.