This is a prospective, single arm, phase II study to assess the effect of nilotinib reduced to half the standard dose for 12 months on treatment-free remission in patients with Chronic Myeloid Leukemia - Chronic Phase (CML-CP) treated with first-line nilotinib who reached a sustained deep molecular response before entering the study.
Name: Nilotinib
Description: Full Treatment-Free Remission (FTFR) is defined as patients with Major Molecular Response (MMR) or better, including those who have totally discontinued treatment during the Treatment-Free Remission (TFR) phase and those who are treated with half the standard dosage. Percentage of patients in full treatment-free remission 96 weeks after the start of the consolidation phase is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL ≤ 0.1% (IS) after 96 weeks by the number of patients who entered the consolidation phase.
Measure: Percentage of patients in full treatment-free remission 96 weeks after the start of the consolidation phase. Time: Baseline of consolidation phase up to 96 weeksDescription: The percentage of patients in sustained DMR at the end of the consolidation phase (week 48). Sustained DMR: ≥ MR 4.0 (BCR-ABL level ≤0.01% IS) in all of the last 4 BCR-ABL RQ-PCR assessments. The proportion of patients in sustained DMR at the end of the consolidation phase (week 48) is calculated by dividing the number of patients in sustained DMR at week 48 by the number of patients who entered the consolidation phase.
Measure: Percentage of patients who remain in sustained Deep Molecular Response (DMR) at the end of the consolidation phase (week 48). Time: Baseline of consolidation phase up to 48 weeksDescription: The percentage of patients in deep molecular response is calculated by dividing the number of patients in DMR (≥ MR 4.0 (BCR-ABL level ≤0.01% IS in all of the last 4 BCR-ABL RQ-PCR assessments) 48, 96 and 144 weeks after the start of the consolidation phase by the number of patients who entered the consolidation phase.
Measure: Percentage of patients who remain in DMR at the end of the consolidation phase (week 48), at 96 weeks and at 144 weeks after the start of the consolidation phase. Time: Baseline of consolidation phase, week 48, 96 and 144Description: The percentage of patients in full treatment-free remission at week 144 is calculated by dividing the number of patients with no loss of MMR (BCR-ABL ≤ 0.1% (IS)) 144 weeks after the start of the consolidation phase by the number of patients who entered the consolidation phase.
Measure: Percentage of patients in full treatment-free remission 144 weeks after the start of the consolidation phase. Time: Baseline of consolidation phase, week 144Description: The percentage of patients with MMR at week 48, 96 and 144 is calculated by dividing the number of patients with MMR at week 48, 96 and 144, regardless of whether they required re-initiation of treatment after the start the study, by the number of patients who entered the consolidation phase.
Measure: Percentage of patients with MMR or better at 48, 96, 144 weeks after starting the consolidation phase Time: Baseline of consolidation phase, week 48, 96 and 144Description: Descriptive statistics of BCR-ABL levels (International scale), measured by quantitative Polymerase Chain Reaction (PCR), over time after re-start of nilotinib therapy up to 144 weeks in patient who failed Treatment Free Remission Phase.
Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcript after re-start of nilotinib therapy in patients who failed Treatment Free Remission Phase. Time: Restart of nilotinib therapy up to approximately 144 weeksDescription: Descriptive statistics of BCR-ABL levels (IS), measured by quantitative PCR, over time after discontinuation of nilotinib therapy in Treatment Free Remission Phase up to 144 weeks.
Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcript after discontinuation of nilotinib therapy in Treatment Free Remission Phase. Time: Discontinuation of nilotinib therapy in patients in TFR phase up to approximately 144 weeksDescription: Descriptive statistics of BCR-ABL levels (IS), measured by quantitative PCR, over time during the consolidation period to 48 weeks.
Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcript during the consolidation period. Time: Baseline of consolidation phase up to 48 weeksDescription: FTFS: time from the start of the consolidation phase to the earliest occurrence of any of the following events: loss of MMR, reinitiation of treatment due to any cause, progression to accelerated phase (AP)/blast crisis (BC), or death due to any cause.
Measure: Full Treatment-Free Survival (FTFS) Time: Baseline of consolidation phase up to 144 weeksDescription: Percentage of patients in TFR at weeks 96 and week 144 is calculated by dividing the number of patients with no loss of MMR and no reinitiation of nilotinib after drug discontinuation at weeks 96 and week 144 by the number of patients who entered the TFR phase.
Measure: Proportion of patients among those who entered the TFR phase with no loss of MMR and no reinitiation of nilotinib after drug discontinuation Time: Baseline of consolidation up to 96 and 144 weeksDescription: TFS: time from the start of the TFR phase to the earliest occurrence of any of the following events: loss of MMR, reinitiation of treatment due to any cause, progression to AP/BC or death due to any cause.
Measure: Treatment-free survival (TFS) Time: From the start of the TFR phase up to Week 144.Description: PFS: time from the start of the consolidation phase to progression to AP/BC or death due to any cause, whichever occurs first.
Measure: Progression-free survival (PFS) after the start of consolidation phase Time: Baseline of consolidation phase up to 144 weeksDescription: PFS: time from the start of the TFR phase to progression to AP/BC or death due to any cause, whichever occurs first.
Measure: Progression Free Survival (PFS) after the start of TFR phase Time: From the start of the TFR phase up to week 144.Description: OS: time from start of the study to death due to any cause.
Measure: Overall Survival (OS) Time: Baseline of consolidation phase up to 144 weeksDescription: To assess safety during the nilotinib treatment consolidation phase, TFR phase and during reinitiation of treatment with nilotinib.
Measure: The number of patients with Adverse Events as measure of safety and tolerability Time: From screening up to approximately week 144Description: Statistical correlation between clinical and laboratory correlates at diagnosis (e.g. Sokal Risk scale, demography, type of BCR-ABL transcript) or during previous treatment (e.g. Early Molecular Response=BCR-ABL transcript measured by quantitative PCR <10% after 3 months of first-line treatment with nilotinib at the dose of 300 mg BID) and the achievement of Full Treatment Free Remission and Treatment Free Remission at 96 weeks
Measure: Correlation between clinical and laboratory factors and clinical outcome Time: Baseline of consolidation phase up to 96 weeksAllocation: N/A
Single Group Assignment
There are 4 SNPs
2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). --- T315I --- --- E255K ---
2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). --- T315I --- --- E255K --- --- Y253H --- --- F359C ---
2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). --- T315I ---
2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). --- T315I --- --- E255K --- --- Y253H ---