An open-label, single center study of oral AMN 107 (nilotinib) in adult patients with imatinib - resistant or - intolerant chronic myeloid leukemia in chronic phase, accelerated phase or blast crisis, previously enrolled in and having completed ENACT (CAMN107A2109) trial in Hungary.
- Conditions
- adult patients with imatinib - resistant or - intolerant CML-CP, CML-AP or CML-BC
- Registration Number
- EUCTR2008-004467-19-HU
- Lead Sponsor
- ovartis Hungary Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Patients under consideration for participation in this study must meet the following inclusion criteria:
1.Imatinib - resistant or - intolerant Philadelphia chromosome-positive CML in chronic phase, accelerated phase or in blast crisis patients previously enrolled to CAMN107A2109 in Hungary and continuing the treatment with nilotinib at the time of enrollment for this trial.
2.According to the opinion of the investigators the patient would benefit from the further treatment with nilotinib.
3.No evidence of extramedullary leukaemic involvement, with the exception of liver and spleen.
4.Males or females =18 years of age.
5.QTc = 450 msec on the average of three serial baseline ECG (using the QTcF formula).
6.Patients must have the following laboratory values:
•Potassium within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication.
•Total calcium (corrected for serum albumin) within normal limits or correctable with supplements.
•Magnesium within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication.
•Phosphorus = LLN or correctable with supplements.
•ALT and AST = 2.5 x ULN or = 5.0 x ULN unless considered due to tumour.
•Alkaline phosphatase = 2.5 x ULN unless considered due to tumour.
•Serum bilirubin = 1.5 x ULN unless considered due to tumour.
•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.
9.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.Known T315I mutations
2.Impaired cardiac function including any one of the following:
•LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram.
•Inability to determine the QT interval on ECG.
•Complete left bundle branch block.
•Use of a ventricular-paced pacemaker.
•Congenital long QT syndrome or a known family history of long QT syndrome.
•History of or presence of clinically significant ventricular or atrial tachyarrhythmias.
•Clinically significant resting brachycardia (< 50 beats per minute).
•QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
•History of clinically documented myocardial infarction.
•History of unstable angina (during the last 12 months).
•Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
3.Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required)
4.Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection)
5.History of significant congenital or acquired bleeding disorder unrelated to cancer
6.Previous radiotherapy to = 25% of the bone marrow
7.Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery
8.History of non-compliance to medical regimens or inability to grant consent
9.Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
10.Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm.
11.Patients actively receiving therapy with strong CYP3A4 inducers (e.g, dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John’s Wort) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm.
12.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
13.History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
14.Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease
15.Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval)
16.Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1.To provide patients with life threatening conditions: imatinib resistant/intolerant chronic myeloid leukemia - in blast crisis, accelerated phase and chronic phase, who have been previously enrolled in to CAMN107A2109 and benefit from the treatment, with access to nilotinib (AMN107) in Hungary until such time as the drug is financed by the National Health Insurance Fund in Hungary or for a period of 12 months, whichever comes first.<br><br><br>;Secondary Objective: 2.To collect additional safety and efficacy data on nilotinib (AMN107) in a population of the patients who will continue the treatment with nilotinib in Hungary after completion of the CAMN107A2109 trial.<br>;Primary end point(s):
- Secondary Outcome Measures
Name Time Method