Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) MedDRA version: 14.1 Level: LLT Classification code 10009012 Term: Chronic myelogenous leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tasigna
Product Name: Tasigna (Nilotinib)
Pharmaceutical Form: Capsule, hard
Current Sponsor code: AMN107/nilotinib
Other descriptive name: Tasigna
Concentration unit: mg milligram(s)
Con
Sponsors
ICORG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male or female patients = 18 years of age •ECOG performance status 0, 1, or 2 •Patients with CML-CP within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). Standard conventional cytogenetic analysis must be done on bone marrow. FISH cannot be used. •Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations in more than one metaphase to prove clonality (where possible a review of up to 20 metaphases is desirable to provide a more accurate assessment of baseline Ph+ chromosome positivity). •Documented chronic phase CML will meet all the criteria defined by: 1. =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of Philadelphia Chromosome with (9,22) translocation •Previously documented T315I mutations •Any medical treatment for CML (including imatinib) prior to study entry for longer than 4 weeks with the exception of Hydroxyurea and/or Anagrelide Impaired cardiac function including any one of the following:- *LVEF450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF>450msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-scanned for QTc. *History of clinically documented myocardial infarction within past 12 months *History of unstable angina (during the last 12 months) *Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension). •Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). •History of significant congenital or acquired bleeding disorder unrelated to cancer. •Major surgery within 4weeks prior to day-1 of study or who have not recovered from prior surgery. •Treatment with other investigational agents within 30 days of Day-1. •History of non-compliance to medical regimens or inability to grant consent •Patients with other primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention •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.htn. The Principal Investigator must be contacted if a patient needs to be started on any of these drugs during study treatment. •Patients actively receiving therapy with strong CYP3A4 inducers, (e.g. Dexamethasone, 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. The Principal Investigator must be contacted if a patient needs to be started on any of these drugs during study treatment. •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). •History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis. •Acute or chronic liver, pancreatic or severe renal disease considered unrelated to CML •Patients who are currently receiving treatment with any medications that have the pot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the Complete Cytogenetic Response Rate at 6 months. ;Secondary Objective: 1.To establish the Complete Cytogenetic Response Rates (CCyR) at 3, 9, 12, 18 and 24 months 2.To establish Molecular Response Rates (MMR/CMR) at 3, 6, 9, 12,18 and 24 months 3.To establish the safety of a twice daily dose of Nilotinib 300mg 4.To correlate pharmacokinetic data with response rates and toxicity 5.To correlate Bcr-Abl results using the GeneXpert system with international standardized QPCR 6.To estimate the prevalence of Bcr-Abl mutations prior to and during therapy with nilotinib ;Primary end point(s): -Cytogenetic response will be assessed every 3 months by bone marrow aspiration, with evaluation of a minimum of 20 metaphases, until achievement of a complete cytogenetic response (CCyR). Molecular response will be assessed every 3 months using quantitative PCR for Bcr-Abl. -The rate of CCyR at 6 months will be the primary efficacy endpoint. -The rate of major and complete molecular responses over time will be secondary efficacy endpoints. -Patients will also undergo assessment for evidence of extramedullary disease The efficacy of Nilotinib 300mg BD will be compared with the efficacy of imatinib (400mg and 800mg) and Nilotinib 400mg BD as front line therapy in studies already reported (IRIS, MD Anderson and Italian studies). | — |
Countries
Germany, Ireland, United Kingdom
Outcome results
None listed