a phase l/ll study of amn107 in adult patients with glivec-intolerant cml or relapsed-refractory ph+all

Conditions: Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)

Summary: this study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving imatinib.


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.

Keywords: chronic myelogenous leukemia acute lymphoblastic leukemia