SNPMiner Trials (Home Page)
Report for Mutation F359C
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 6 clinical trials
Clinical Trials
1 A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
NCT01456676 Philadelphia Chromosome Positive Chronic Myelogenous Leukemia Drug: Nilotinib + LDE225 MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Philadelphia Chromosome
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia
Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K --- --- T315I --- --- F359C ---
Primary Outcomes
Description: Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
Measure: Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy Time: 56 days (2 treatment cycles at 28 days each)Secondary Outcomes
Description: Assessment of the safety and tolerability profile of nilotinib in combination with LDE225
Measure: No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms Time: 336 days (12 treatment cycles)Description: Assessment of the PK characteristics of nilotinib administered in combination with LDE225
Measure: Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) Time: 50 daysDescription: Determination of the kinetics of major molecular response
Measure: Major molecular response (MMR) rates at 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of the kinetics of complete molecular response
Measure: Complete molecular response (CMR) rates at 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of major cytogenetic response rates
Measure: Major cytogenic response (MCyR) rates by 3, 6 and 12 months Time: 336 days (12 treatment cycles)Description: Determination of complete cytogenetic response rates
Measure: Complete cytogenic response (CCyR) rates by 3, 6 and 12 months Time: 336 days (12 treatment cycles)2 Dynamics of ABL Mutations in Imatinib Failed Ph Positive or Bcr-Abl Positive CML CP or AP Patients Who Treated With Nilotinib as Second-line TKI Therapy (AMICAN-Prospective)in Asia
The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and expression of new point mutations during nilotinib treatment.
NCT01562847 Chronic Myeloid Leukemia Drug: Nilotinib MeSH:Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E --- --- Q252H --- --- Y253F --- --- E255K --- --- F359C ---
Primary Outcomes
Measure: To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment Time: 5 yearsSecondary Outcomes
Measure: To analyze and evaluate the overall survival and disease free survival in the nilotinib treatment according to progression of the disease and types of point mutations Time: 5 years3 A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib
A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.
NCT01698905 Chronic Myeloid Leukemia Drug: nilotinib MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia
Written informed consent obtained prior to any screening procedures Exclusion Criteria: 1. Prior AP, BC or allo-transplant 2. Patient has documented MR4.5 at the time when switched from imatinib to nilotinib 3. Patients with known atypical transcript 4. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a 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) 5. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months 6. --- T315I --- --- E255K --- --- Y253H --- --- F359C ---
Primary Outcomes
Description: TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmationTFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.
Measure: Percentage of patients in Treatment Free Remission (TFR) within 48 weeks Time: First 48 weeks following nilotinib cessation.Secondary Outcomes
Description: TFR is defined as no confirmed loss of MR4 (molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation.TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.
Measure: Percentage of patients in Treatment Free Remission (TFR) within 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years Time: 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessationDescription: Kaplan-Meier (KM) estimation of PFS. PFS is measured from the date of start of nilotinib TFR phase (cessation of nilotinib) to the date of the earliest of the event: progression to AP/BC, or death from any cause. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval right-censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up.
Measure: Progression free survival (PFS) to Accelerated phase/Blast crisis (AP/BC) or death Time: nilotinib cessation up to approximately 580 weeksDescription: TFS is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4, re-start of nilotinib treatment, progression to AP/BC or death from any cause. Patients not known to have had any of the events or died on or before the cut-off date for the KM analysis will have their TFS interval right-censored at the earlier of the date of their last assessment (PCR, cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up.
Measure: Treatment free survival (TFS) Time: nilotinib cessation up to approximately 580 weeksDescription: Kaplan-Meier (KM) estimation of OS. OS is measured from the date of start of nilotinib TFR phase to the date of death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
Measure: Overall survival (OS) Time: nilotinib cessation up to approximately 580 weeksDescription: Descriptive statistics of BCR-ABL over time after re-start of nilotinib therapy. ABL= Abelson leukemia virus and BCR=Break point cluster region
Measure: Change in BCR-ABL (oncoprotein product of BCR-ABL fusion gene) transcripts after re-start of nilotinib therapy Time: re-start of nilotinib up to approximately 48 weeksDescription: Percentage of patients who are in stable MMR (stable MMR=BCR-ABL ≤ 0.1% IS) at 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks is calculated by dividing the number of patients achieving MMR any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240,288,336, 384, and 432 weeks after the first achievement of MMR, irrespective of whether there is loss of MMR in between, by the number of patients who achieved MMR at any time during the nilotinib re-initiation phase
Measure: Percentage of patients with stable MMR in nilotinib re-initiation phase Time: start of nilotinib in re-initiation phase up to approximately 432 weeksDescription: Percentage of patients who are in stable MR4 (stable MR4=BCR-ABL ≤ 0.01% IS) at 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240,288,336, 384, and 432 weeks after the first achievement of MR4, irrespective of whether there is loss of MR4 in between, by the number of patients who achieved MR4 at any time during the nilotinib re-initiation phase
Measure: Percentage of patients with stable MR4 in nilotinib re-initiation phase Time: start of nilotinib in re-initiation phase up to approximately 432 weeksDescription: Percentage of patients who are in stable MR4.5 (stable MR4.5=BCR-ABL ≤ 0.0032% IS) at 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240,288 ,336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4.5 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240,288,336, 384, and 432 weeks after the first achievement of MR4.5, irrespective of whether there is loss of MR4.5 in between, by the number of patients who achieved MR4.5 at any time during the nilotinib re-initiation phase
Measure: Percentage of patients with stable MR4.5 in nilotinib re-initiation phase Time: start of nilotinib in re-initiation phase up to approximately 432 weeks4 A PHASE I/II, MULTI-CENTRE, TRIAL OF RUXOLITINIB THERAPY IN COMBINATION WITH NILOTINIB IN PATIENTS WITH PHILADELPHIA POSITIVE CHRONIC MYELOID LEUKEMIA OR ACUTE LYMPHOBLASTIC LEUKEMIA WHO HAVE FAILED TYROSINE KINASE INHIBITOR THERAPY
This is the study to test combination regimen of Nilotinib and Ruxolitinib therapy for the treatment of patients with Philadelphia positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) who is resistant to multiple tyrosine kinase inhibitor therapies with BCR-ABL kinase inhibition activity. Ruxolitinib is a tyrosine kinase inhibitor blocking alternative pathway independent of BCR-ABL mediated pathway, thus having a potential to overcome tyrosine kinase inhibitor resistance in Philadelphia positive CML or ALL patients. Phase I study will be conducted to define a recommended phase II dose (RPTD) and phase II study will examine the hypothesis that combinational approach will increase response rate of resistant CML/ALL patients, thus evaluating efficacy of the combination regimen.
NCT01914484 Chronic Phase Chronic Myeloid Leukemia Accelerated Phase Chronic Myeloid Leukemia Blastic Phase Chronic Myeloid Leukemia Philadelphia Positive Acute Lymphoblastic Leukemia Resistant to Tyrosine Kinase Inhibitor Therapy Drug: Nilotinib Drug: Ruxolitinib MeSH:Leukemia Leukemia, Myeloid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Blast Crisis Leukemia, Myeloid, Chronic-Phase Leukemia, Myeloid, Accelerated Phase
HPO:Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia
Developed the T315I, T315A Y253H, E255K/V or F359C/V mutation after any TKI therapy. --- T315I --- --- T315A --- --- Y253H --- --- E255K --- --- F359C ---
Primary Outcomes
Description: Maximum Tolerated Dose (MTD) of Ruxolitinib with fixed dose of Nilotinib. Dose escalation will follow a 3+3 study design. The CTCAE v4.03 criteria will be used. Grade 4 toxicity will be accounted as dose limiting toxicity (DLT).
Measure: Phase I: Maximum Tolerated Dose (MTD) Time: Average of 6 monthsDescription: Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow from CML and ALL patients
Measure: Phase II: Major cytogenetic response Time: Average of 6 monthsSecondary Outcomes
Description: Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in CML patients in AP or BP, and patients with Ph+ ALL.
Measure: Phase I: complete hematologic response Time: Average of 3 monthsDescription: Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow taken at 6 months.
Measure: Phase I: major cytogenetic response Time: Average of 6 monthsDescription: It will be defined by NCI Common Terminology Criteria for Adverse Events (CTCAE)version 4.03 for adverse event reporting.
Measure: Phase I: Safety and tolerability Time: Average of 6 monthsDescription: Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in the CML patients in AP or BP and in patients with Ph+ ALL.
Measure: Phase II: complete hematologic response Time: Average of 3 monthsOther Outcomes
Description: Cmax will be measured for the maximum plasma concentration of nilotinib after oral administration.
Measure: Phase II (exploratory): pharmacokinetic profile of combination of Nilotinib with Ruxolitinib Time: During first 24 hours of first dose5 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 Drug: Nilotinib MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia
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 ---
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 weeksSecondary 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 weeksDescription: 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 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 at 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 at 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: Every 3 months after 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: 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 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: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeksDescription: 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 weeks6 Multicenter, Open-Label, Single Arm, Phase II Exploratory Study to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response (ResToP)
The purpose of the present study is to determine the rate of successful treatment-free remission (TFR) within the first 52 weeks following cessation of ponatinib treatment in patients who achieved MR4. Eligible patients had been previously treated with TKI and when patients achieved an optimal molecular response, TKI treatment was discontinued. After loss of response, patients were treated again with a TKI treatment and have documented MR4 for one year at the time of switch to ponatinib to study entry. MR4 is defined as BCR-ABL transcript level ≤ 0.01% IS or undetectable BCR-ABL levels with sample sensitivity of at least 4 log.
NCT04160546 Chronic Myeloid Leukemia, Chronic Phase Drug: Ponatinib 15 MG Drug: Acetylsalicylic acid 100 MG MeSH:Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO:Chronic myelogenous leukemia Myeloid leukemia
3. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a 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 ---
Primary Outcomes
Description: This variable is defined as the number of patients who have a maintained MMR and have not restarted TKI therapy in the first 52 weeks after starting ponatinib TFR phase divided by the number of patients who entered ponatinib TFR phase.
Measure: Proportion of patients with a maintained MMR within 52 weeks following ponatinib Treatment-Free Remission (TFR) Time: 52 weeksSecondary Outcomes
Description: The number and percentage of patients with treatment-emergent adverse events (new or worsening from baseline) will be summarized by system organ class (SOC) and/or preferred term (PT), severity (based on CTCAE grades), type of adverse event and relation to study treatment.
Measure: Evaluate the toxicity and safety profile of 15 mg/24h dose treatment of ponatinib combined with ASA. Time: 104 weeksDescription: The number and percentage of patients with thromboembolic events will be summarized by preferred term, severity (based on CTCAE grades), type of adverse event, relation to study treatment by the phases or subsets previously described.
Measure: Evaluate thromboembolic events for study period. Time: 104 weeksDescription: The number and percentage of patients with hemorrhagic events will be summarized by preferred term, severity (based on CTCAE grades), type of adverse event, relation to study treatment by the phases or subsets previously described.
Measure: Evaluate hemorrhagic events for study period. Time: 104 weeksDescription: The number and percentage of patients with hemolytic events will be summarized by preferred term, severity (based on CTCAE grades), type of adverse event, relation to study treatment by the phases or subsets previously described.
Measure: Evaluate hemolytic events for study period. Time: 104 weeksDescription: The number and percentage of patients with gastrointestinal events will be summarized by preferred term, severity (based on CTCAE grades), type of adverse event, relation to study treatment by the phases or subsets previously described.
Measure: Evaluate gastrointestinal events for study period. Time: 104 weeksDescription: Number of patients still in MR4 and have not restarted TKI therapy in the first 52 weeks after starting ponatinib TFR phase divided by the number of patients who entered ponatinib TFR phase.
Measure: Evaluate the proportion of patients still in MR4 (BCR-ABL ≤ 0.01%) within 52 weeks following ponatinib therapy cessation. Time: 52 weeksDescription: The number of patients who still have a MMR and have not restarted TKI therapy in the first 24 weeks after starting ponatinib TFR phase divided by the number of patients who entered ponatinib TFR phase.
Measure: Evaluate the proportion of patients still in MMR within 24 weeks following ponatinib therapy cessation. Time: 24 weeksDescription: Number of patients with each clinical response obtained after stop Ponatinib treatment classified with subject´s physical activity frequency during 52 weeks
Measure: Evaluate the effects of physical activity on treatment response Time: 52 weeksDescription: Time from start ponatinib treatment to the occurrence of progression to AP/BC, loss of MMR or death from any cause, the earliest of these events.
Measure: To estimate progression-free survival (PFS) Time: 4 yearsDescription: time from ponatinib cessation to the occurrence of loss of MMR, restart of TKI treatment, progression of AP/BC, or death from any cause, the earliest of these events.
Measure: Treatment-free survival (TFS) Time: 104 weeksOther Outcomes
Description: The number of patients who achieve a MR 5 at ponatinib therapy cessation divided by the number of patients who entered ponatinib TFR phase.
Measure: Evaluate the proportion of patients who achieve a MR 5 at ponatinib therapy cessation. Time: 104 weeks