E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment of the hematologic malignancies |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009013 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the safety profile of AMN107 in a large number of patients. 2. To provide patients with life threatening conditions imatinib resistant/intolerant chronic myeloid leukemia - in blast crisis, accelerated phase and chronic phase, with expanded access to AMN107 until such time as the product is ommercially available. |
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E.2.2 | Secondary objectives of the trial |
To further evaluate the therapeutic effect and assess the efficacy of AMN107. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients under consideration for participation in this study must meet one of the following disease inclusion criteria as defined in 1, 2, or 3. Inclusion criteria number 4 applies to all three groups CML-BC, CML-AP, and CML- CP. 1. Imatinib - resistant or - intolerant Philadelphia chromosome-positive CML in blast crisis defined as at least 30 blasts in peripheral blood and/or bone marrow or extramedullary disease excluding liver and spleen 2. Imatinib - resistant or - intolerant Philadelphia chromosome-positive CML patients in accelerated phase defined with one or more of the following criteria present within 4 weeks prior to beginning treatment 8805; 15 but 30 blasts in blood or bone marrow 8805; 30 blasts plus promyelocytes in peripheral blood or bone marrow providing that 30 blasts present in bone marrow peripheral basophils 8805; 20 thrombocytopenia 100 X 109/L unrelated to therapy 3. Imatinib - resistant or - intolerant Philadelphia chromosome-positive CML in chronic phase defined with the following criteria 15 blasts in peripheral blood and bone marrow 30 blasts plus promyelocytes in peripheral blood and bone marrow 20 basophils in the peripheral blood 8805; 100 x 109/L 8805; 100,000/mm3 platelets No evidence of extramedullary leukemic involvement, with the exception of liver and spleen 4. CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible 5. Males or females 8805;18 years of age |
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E.4 | Principal exclusion criteria |
1. Cytopathologically confirmed CNS infiltration. in absence of suspicion of CNS involvement, lumbar puncture is not required 2. 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 on screening ECG using the QTcF formula The ICH guideline criterion of 450 msec has been increased to 480 msec to allow patient with this life threatening disease where no medication is currently approved, providing an acceptable benefit-risk for the patient. 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 3. Use of therapeutic coumarin derivatives i.e., warfarin, acenocoumarol, phenprocoumon up to the day before study drug administration 4. Acute or chronic liver or renal disease considered unrelated to tumor |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evalaution of the safety and further information on the efficacy of AMN107 in adult patients with imatinib Glivec/Gleevec resistant or intolerant chronic myeloid leukemia in blast crisis, accelerated phase or chronic phase |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |