This is an open label, non randomized, prospective, multicenter, phase II clinical trial evaluating nilotinib 400 mg BID for the treatment of newly diagnosed CML-AP patients. Patients enrolled into the study will receive 400mg of nilotinib, orally, twice daily (800mg/day)
Name: AMN107
Description: The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.
Measure: To evaluate the safety and tolerability profile of nilotinib in newly diagnosed CML-AP Time: 12 monthDescription: To test the efficacy of nilotinib 400 mg BID in inducing complete cytogenetic response (CCyR) at 12 months in newly diagnosed CML-AP patients
Measure: To test the efficacy of nilotinib 400 mg BID Time: 12 monthsDescription: Evaluate the rate of complete hematologic response (CHR) with nilotinib 400 mg BID at 3 months.
Measure: Evaluate the rate of complete hematologic response (CHR) Time: 3 monthsDescription: Evaluate the Quality of Life by FACT-Leu Version 4 questionnaire at 3, 6, 9, 12, 15, 18 and 24 months.
Measure: Evaluate the Quality of Life Time: 3, 6, 9, 12, 15, 18 and 24 monthsDescription: Evaluate the median time to achieve molecular response and the cumulative probability of obtaining molecular response during the first 2 years of treatment. This will be undertaken through the analysis of the best molecular response at 3, 6, 12, 18 and 24 months. MMR will be preferred and it will be defined as a BCR-ABL/ABL ratio ≤ 0.1% IS using RQ-PCR, but any log reduction between 1 and 4,5 logs will be considered a molecular response.
Measure: Evaluate the median time to achieve molecular response Time: uring the first 2 years of treatmentDescription: Evaluate the proportion of patients achieving CCyR at 3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 months as well as the duration of sustained response.
Measure: Evaluate the proportion of patients achieving CCyR Time: 3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 monthsDescription: To correlate the probability of reaching MMR, CMR and CCyR with the risk of progression to blastic phase, relapse and overall survival.
Measure: To correlate the probability of reaching MMR, CMR and CCyR Time: 2 yearsAllocation: Non-Randomized
Single Group Assignment
There is one SNP
- Treatment with tyrosine kinase inhibitors or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with the exception of HU and/or anagrelide - Previously documented T315I mutations; - Uncontrolled congestive heart failure or hypertension; - Myocardial infarction or unstable angina pectoris within past 12 months; - Significant arrhythmias, including history or presence of clinically significant ventricular or atrial tachyarrhythmias, clinically significant bradycardias, long QT syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula). --- T315I ---