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A phase IA/II multicenter, dose-escalation study of oral AMN107 on a continuous daily dosing schedule in adult patients with Gleevec-resistant/intolerant CML in chronic or accelerated phase or blast crisis, relapsed/refractory Ph+ ALL and other hematological malignancies - NA

Conditions
CML in accelerated or chronic phase or blast crisis, relapsed/refractory Ph+ ALL, systemic mastocytosis, or hypereosinophilic syndrome.
MedDRA version: 14.0Level: LLTClassification code 10009700Term: CMLSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Registration Number
EUCTR2004-001483-51-GB
Lead Sponsor
ovartis Pharma Services AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
955
Inclusion Criteria

Patients must have the following laboratory values:
Potassium = LLN (lower limit of normal) or correctable with supplements
Total calcium (corrected for serum albumin) = LLN or correctable with supplements
Magnesium = LLN or correctable with supplements
Phosphorus = LLN or correctable with supplements
ALT and AST = 2.5 x ULN or = 5.0 x ULN if considered due to tumor
Alkaline phosphatase = 2.5 x ULN
Serum bilirubin = 1.5 x ULN
Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance ? 50 ml/min

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 MUGA scan or 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 (> 450 msec in Phase II) 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
•Angina pectoris (unstable angina pectoris diagnosed or treated during the last 12 months in Phase II)
•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
•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, GM-CSF) = 1 week prior to starting study drug. Erythropoietin is allowed.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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