An open-label, multicenter, expanded access study of oral AMN 107 in adult patients with Imatinib (Glivec®/Gleevec®) - resistant or - intolerant chronic myeloid leukemia in blast crisis, accelerated phase or chronic phase - NA
- Conditions
- CML in accelerated phase, blast crisis and chronic phase
- Registration Number
- EUCTR2005-001818-41-PT
- Lead Sponsor
- ovartis Pharma Services
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2000
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:
•= 15% but < 30% blasts in blood or bone marrow
•= 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that < 30% blasts present in bone marrow)
•peripheral basophils = 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
•= 100 x 109/L (= 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
The following inclusion criteria are mandatory for all patients:
5.Males or females =18 years of age
6.WHO Performance Status of = 2
7.Patients must have the following laboratory values:
•Potassium within normal limits or correctable with supplements
•Total calcium (corrected for serum albumin) within normal limits 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 unless considered due to tumor
•Serum bilirubin = 1.5 x ULN
•Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance ? 50 ml/min
•Serum amylase = 1.5 x ULN and serum lipase = 1.5 x ULN
8.Written signed and dated informed consent prior to any study procedures being performed
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
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
5.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
6.Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) = 1 week prior to starting study drug.
7.Patients who are currently receiving treatment with any of the medications that have the potential to prolong the QT interval (Post-text supplement 2).
8.Patients who have received chemotherapy = 1 week or who are within 5 half-lives of their last dose of chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy. Patients who have received imatinib = 1 week or who have not recovered from side effects of such therapy.
9.Patients who have received immunotherapy =1 week prior to starting study drug or who have not recovered from side effects of such therapy
10.Patients who have received any investigational drug = 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
11.Patients who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation < 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
12.Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
13.Known diagnosis of human deficiency virus (HIV) infection (HIV testing is not mandatory)
14.Patient with a history of another malignancy that is currently clinically significant or currently requires active intervention.
15.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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1.To evaluate the safety profile of AMN107 in a large number of patients.<br>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 commercially available.<br>;Secondary Objective: Not applicable;Primary end point(s): Not applicable
- Secondary Outcome Measures
Name Time Method