A Phase l/ll Study of AMN107 in Adult Patients With Glivec-intolerant CML or Relapsed-refractory Ph+ALL
- Conditions
- Chronic Myelogenous LeukemiaAcute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)
- Interventions
- Registration Number
- NCT00384228
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving Imatinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- 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
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Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS involvement, lumbar puncture is not required
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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
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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)
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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)
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Use of therapeutic warfarin
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Acute or chronic liver or renal disease considered unrelated to tumor (e.g., hepatitis, cirrhosis, renal insufficiency, etc.)
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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
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Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1 week prior to starting study drug.
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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.
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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.
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Patients who have received Glivec® ≤ 1 week or who have not recovered from side effects of such therapy.
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Patients who have received immunotherapy ≤ 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
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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.
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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.
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Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
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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
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Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
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Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
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Patients unwilling or unable to comply with the protocol
Other protocol-defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nilotinib Nilotinib -
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) profile of single and multiple doses day 1 and 15 of cycle 1,day 6, 8, 10, 12, 22 and 28 of cycle 1, day 15 of cycle 2 Safety evaluation assessed by dose limiting toxicity within first cycle of 28 day treatment and AEs within 3 cycles every first 28 days
- Secondary Outcome Measures
Name Time Method Anti-leukemic activity within 3 cycles of 28 days treatment Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study completion Bone marrow and/or blood assessments to detect the presence of Bcr-Abl transcript and mutational analysis of Bcr-Abl before, during and after therapy. Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study comp
Trial Locations
- Locations (1)
Novartis Investigative Site
🇯🇵Tokyo, Japan