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Report for Clinical Trial NCT03874858

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II, Single-arm, Multicenter Study of Full Treatment-free Remission in Patients With Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib in First-line Therapy Who Have Achieved a Sustained, Deep Molecular Response for at Least 1 Year

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 CML-CP treated with first-line nilotinib who reached a sustained deep molecular response before entering the study.

NCT03874858 Chronic Myeloid Leukemia
MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia

1 Interventions

Name: Nilotinib

Description: Nilotinib oral 300 mg QD hard capsules
Type: Drug
Group Labels: 1

nilotinib


Primary Outcomes

Description: 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 weeks

Secondary Outcomes

Description: The percentage of patients in sustained DMR at the end of the consolidation phase (week 48). Sustained DMR: Molecular Response (MR) 4.5 (IS) or undetectable MR4.0 with assay sensitivity of 4.0 log in 3 of the 4 BCR-ABL qPCR monthly assessments performed every 4 months, and with the last assessment in MR4.5 or undetectable MR4 before entering the TFR 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 weeks

Description: The percentage of patients in deep molecular response is calculated by dividing the number of patients in DMR (MR4.5 or undetectable MR4.0) 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 at week 48, 96 and 144

Description: 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 at week 144

Description: 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 at week 48, 96 and 144

Description: 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: Every 3 months after restart of nilotinib therapy up to approximately 144 weeks

Description: 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: Monthly up to week 96, every 12 weeks up to approximately week 144 after discontinuation of nilotinib therapy .

Description: 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 weeks

Description: 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 weeks

Description: 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 weeks

Description: 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 weeks

Description: 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 144

Description: 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 weeks

Description: To characterize the kinetics of BCR-ABL transcripts after restart of nilotinib therapy in patients who failed Treatment Free Remission (TFR) phase.

Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcripts after restart of nilotinib therapy in patients who failed TFR phase.

Time: Restart of nilotinib therapy in Follow Up Phase up to approximately 144 weeks

Description: To characterize the kinetics of BCR-ABL transcripts after discontinuation of nilotinib therapy in TFR Phase.

Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcripts after discontinuation of nilotinib therapy in TFR Phase

Time: Discontinuation of nilotinib therapy in patients in TFR phase up to approximately 144 weeks

Description: To characterize the kinetics of BCR-ABL transcripts during the consolidation period.

Measure: Change in Polymerase Chain Reaction (PCR) of BCR-ABL transcripts during the consolidation period.

Time: Baseline of consolidation phase up to 48 weeks

Description: Identify which factors are associated with the successful of FTFR and TFR (no loss of MMR and no reinitiation of nilotinib therapy)in the first 96 weeks following the study start. Possible factors: patient demography, Sokal risk category, Early Molecular Response (EMR), type of transcript)

Measure: Correlation of factors associated with the successful clinical outcome to the treatment up to 96 weeks

Time: Baseline of consolidation phase up to approximately 96 weeks

Description: To characterize the kinetics of BCR-ABL transcripts after restart of nilotinib therapy in patients who failed Treatment Free Remission (TFR) phase.

Measure: The change of the kinetics of BCR-ABL transcripts after restart of nilotinib therapy in patients who failed TFR phase.

Time: Restart of nilotinib therapy in Follow Up Phase until week 144.

Description: To characterize the kinetics of BCR-ABL transcripts after discontinuation of nilotinib therapy in TFR Phase.

Measure: The change of the kinetics of BCR-ABL transcripts after discontinuation of nilotinib therapy in TFR Phase

Time: Discontinuation of nilotinib therapy in patients in TFR phase until week 144.

Description: To characterize the kinetics of BCR-ABL transcripts during the consolidation period.

Measure: The change of the kinetics of BCR-ABL transcripts during the consolidation period.

Time: Baseline of consolidation phase up to 48 weeks

Description: Identify the factors correlated to the successful of FTFR and TFR (no loss of MMR and no reinitiation of nilotinib therapy)in the first 96 weeks following the study start.

Measure: Identification of factors related to the clinical outcome to the treatment

Time: Baseline of consolidation phase up to approximately 96 weeks

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 4 SNPs

SNPs


1 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 ---


2 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 --- --- E255K --- --- Y253H --- --- F359C ---


3 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 ---


4 Y253H

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 ---



HPO Nodes


HPO: