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Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia (HALF)

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ClinicalTrials.gov Identifier: NCT04147533
Recruitment Status : Not yet recruiting
First Posted : November 1, 2019
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Masaryk University

Brief Summary:
Evaluation of the efficacy and safety of withdrawal of tyrosine kinase inhibitors after previous two-step dose reduction in patients with chronic myeloid leukemia in deep molecular remission

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia, Chronic Phase Withdrawal;Drug Drug: Imatinib withdrawal Drug: Dasatinib Drug: Nilotinib Phase 2

Detailed Description:

In the first phase of the study (first 6 months after the study enrollment), 50% reduction of standard TKI dose follows.Physical and clinical examinations (focused on adverse effects and possible withdrawal syndrome manifestation) will be performed in predefined time intervals, pharmacological history of the subject will be taken, mandatory biochemical, hematological, and molecular-biological examinations will be performed.

In the following 6 months, the dose will be reduced by 50% i.e. medication will be administered every other day.

Twelve months after enrollment, the medication will be stoped. The subject is followed in predefined time intervals.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Prospective Phase II Clinical Trial Evaluating the Efficacy and the Safety of Tyrosine Kinase Inhibitors Withdrawal After a Previous Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia in Deep Molecular Remission
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: initially treated patients
The dose of tyrosin kinase inhibitors (imatinib, or nilotinib, or dasatinib) in patients meeting all of the inclusion criteria and none of the exclusion criteria will be reduced in two consequent steps, during the first 6 months after study entry by 50%, during the second 6 months by 50% again; the medication is discontinued then and the patients are followed each month in the first 6 months after withdrawal, each 1,5 month in the next 6 months, and each 3 months in the next 12 months.
Drug: Imatinib withdrawal
withdrawal of imatinib after previous two-step dose reduction: during the first 6 months after study entry, the dose of imatinib is 50% of the standard dose (200 mg daily), during the second 6 months after study entry, the dose of imatinib is 200 mg every other day; 12 months after study entry, imatinib is discontinued, the patient is followed in line with the aims of the trial
Other Name: Glivec withdrawal

Drug: Dasatinib
withdrawal of dasatinib after previous two-step dose reduction: during the first 6 months after study entry, the dose of dasatinib is 50% of the standard dose (40 mg daily; tablets containing 50 mg are not available on the market), during the second 6 months after study entry, the dose of dasatinib is 40 mg every other day; 12 months after study entry, dasatinib is discontinued, the patient is followed in line with the aims of the trial
Other Name: Sprycel withdrawal

Drug: Nilotinib
withdrawal of nilotinib after previous two-step dose reduction: during the first 6 months after study entry, the dose of nilotinib is 50% of the standard dose (200 mg every 12 hours), during the second 6 months after study entry, the dose of nilotinib is 400 mg every other day; 12 months after study entry, nilotinib is discontinued, the patient is followed in line with the aims of the trial
Other Name: Tasigna withdrawal




Primary Outcome Measures :
  1. proportion of patients in major molecular response, and MRFS at month 6 [ Time Frame: 6 months after entry ]
    Proportion of patients in major molecular response (MMR) ie BCR-ABL1 (oncogenic BCR-ABL gene fusion) transcript levels <= 0.1%) and Molecular Recurrence-Free Survival (MRFS, ie time from study entry to MMR loss, ie BCR-ABL1 transcript levels > 0.1% in 2 consecutive samples, or death from any cause) at month 6 after study entry

  2. proportion of patients in major molecular response (MMR) and MRFS at month 12 [ Time Frame: 12 months after study entry ]
    Proportion of patients in major molecular response (MMR) and MRFS at month 12 after study entry

  3. proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 18 after study entry, ie. 6 months after treatment withdrawal [ Time Frame: 18 months after study entry ]
    The proportion of patients in MMR without treatment (TFR) and treatment-free survival (TFS, ie the time from withdrawal of TKI (tyrosin kinase inhibitors) to loss of MMR, reinitiation of TKI therapy from any cause, progression, or death from any cause) at month 18 after study entry, ie, 6 months after treatment discontinuation

  4. proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 24 after study entry, ie. 12 months after treatment withdrawal [ Time Frame: 24 months after study entry ]
    The proportion of patients in MMR without treatment (TFR) and treatment-free survival (TFS, ie the time from withdrawal of TKI to loss of MMR, reinitiation of TKI therapy from any cause, progression, or death from any cause) at month 24 after study entry, ie 12 months after treatment discontinuation

  5. proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 36 after study entry, ie. 24 months after treatment withdrawal [ Time Frame: 36 months after study entry ]
    The proportion of patients in MMR without treatment (TFR) and treatment-free survival (TFS, ie the time from withdrawal of TKI to loss of MMR, reinitiation of TKI therapy from any cause, progression, or death from any cause) at month 36 after study entry, ie 24 months after treatment discontinuation


Secondary Outcome Measures :
  1. Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 will recover after TKI re-introduction [ Time Frame: every two months in the first 12 months, at early termination (due to pregnancy, investigator's,national competent authority's or sponsor's decision, poor adherence) ]
    Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 (deep molecular response, level of BCR-ABL transcripts <0.01% related to the international scale) will recover after TKI re-introduction

  2. Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction [ Time Frame: every month between month 13 and 18, every 1.5 month between month 18 and 24, every 3 months between month 24 and 36, at time of early termination ]
    Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction

  3. Time to re-establish MMR and MR4.0 after TKI restart [ Time Frame: since TKI restart until MMR and MR4.0 recovered (only in case that restart is necessary) ]
    Time to re-establish MMR and MR4.0 after TKI restart - evaluation every 3 months after TKI restart

  4. Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal [ Time Frame: every two months in the first 12 months, at early termination (due to pregnancy, investigator's,national competent authority's or sponsor's decision, poor adherence) ]
    Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)

  5. Assessment of TKI withdrawal syndrome - proportion of patients with development of withdrawal syndrome [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of TKI withdrawal syndrome - proportion of patients with development of withdrawal syndrome) (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)

  6. Assessment of TKI withdrawal syndrome - severity of symptoms [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of TKI withdrawal syndrome - severity of symptoms (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)

  7. Assessment of TKI withdrawal syndrome - time to first complaint [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of TKI withdrawal syndrome - time to first complaint

  8. Assessment of TKI withdrawal syndrome - duration of complaints [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of TKI withdrawal syndrome - duration of complaints

  9. Assessment of TKI withdrawal syndrome - therapeutic intervention [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of TKI withdrawal syndrome - therapeutic intervention (pharmacological history, dose changes)

  10. Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)

  11. BCR-ABL1 kinetics during TKI therapy [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    number of BCR-ABL1 transcripts during TKI therapy

  12. Correlation of BCR-ABL1 kinetics (number of BCR-ABL1 transcripts in time) during TKI therapy with potential molecular relapse after TKI discontinuation [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Correlation of BCR-ABL1 kinetics during TKI therapy with potential molecular relapse after TKI discontinuation

  13. Correlation of the effect of TKI dose reduction and subsequent discontinuation with lipid metabolism and glycemia (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades) [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Correlation of the effect of TKI dose reduction and subsequent discontinuation with lipid metabolism and glycemia (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)


Other Outcome Measures:
  1. failure-free survival [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    failure-free survival

  2. progression-free survival [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    progression-free survival

  3. overall survival [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    overall survival

  4. Assessment of correlation of age with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of age with success of TFR / survival without molecular recurrence

  5. Assessment of correlation of gender with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of gender with success of TFR / survival without molecular recurrence

  6. Assessment of correlation of Sokal index (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of Sokal index (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence

  7. Assessment of correlation of Hasford score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of Hasford score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence

  8. Assessment of correlation of EUTOS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of EUTOS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence

  9. Assessment of correlation of ELTS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of ELTS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence

  10. Assessment of correlation of BCR-ABL1 transcript type with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of BCR-ABL1 transcript type with success of TFR / survival without molecular recurrence

  11. Assessment of correlation of previous interferon alfa therapy (yes/no) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of previous interferon alfa therapy (yes/no) with success of TFR / survival without molecular recurrence

  12. Assessment of correlation of previous interferon alfa therapy length with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of previous interferon alfa therapy length with success of TFR / survival without molecular recurrence

  13. Assessment of correlation of TKI type - imatinib - with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of TKI type - imatinib - with success of TFR / survival without molecular recurrence

  14. Assessment of correlation of TKI type - nilotinib - with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of TKI type - nilotinib - with success of TFR / survival without molecular recurrence

  15. Assessment of correlation of TKI type - dasatinib - with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of TKI type - dasatinib - with success of TFR / survival without molecular recurrence

  16. Assessment of correlation of length of imatinib therapy prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of length of imatinib therapy prior to study entry with success of TFR / survival without molecular recurrence

  17. Assessment of correlation of length of dasatinib therapy prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of length of dasatinib therapy prior to study entry with success of TFR / survival without molecular recurrence

  18. Assessment of correlation of length of nilotinib therapy prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of length of nilotinib therapy prior to study entry with success of TFR / survival without molecular recurrence

  19. Plasma concentration of imatinib prior to study entry [ Time Frame: day 0 ]
    Plasma concentration of imatinib prior to study entry

  20. Plasma concentration of imatinib during dose deescalation period [ Time Frame: month 6, 12 ]
    Plasma concentration of imatinib during dose deescalation period

  21. Plasma concentration of nilotinib prior to study entry [ Time Frame: day 0 ]
    Plasma concentration of nilotinib prior to study entry

  22. Plasma concentration of nilotinib during dose deescalation period [ Time Frame: month 6, 12 ]
    Plasma concentration of nilotinib during dose deescalation period

  23. Plasma concentration of dasatinib prior to study entry [ Time Frame: day 0 ]
    Plasma concentration of dasatinib prior to study entry

  24. Plasma concentration of dasatinib during dose deescalation period [ Time Frame: month 6, 12 ]
    Plasma concentration of dasatinib during dose deescalation period

  25. Assessment of correlation of imatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of imatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence

  26. Assessment of correlation of imatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of imatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence

  27. Assessment of correlation of nilotinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of nilotinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence

  28. Assessment of correlation of nilotinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of nilotinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence

  29. Assessment of correlation of dasatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of dasatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence

  30. Assessment of correlation of dasatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of dasatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence

  31. Assessment of correlation of time needed to establish DMR after TKI start with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of time needed to establish DMR after TKI start with success of TFR / survival without molecular recurrence

  32. Assessment of correlation of deep molecular response length prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of deep molecular response length prior to study entry with success of TFR / survival without molecular recurrence

  33. Assessment of correlation of molecular response depth (MMR i.e. BCR-ABL1<=0,1% vs. DMR i.e. BCR-ABL1<=0,01%) at study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of molecular response depth (major molecular response i.e. BCR-ABL1<=0,1% vs. deep molecular response i.e. BCR-ABL1<=0,01%) at study entry with success of TFR / survival without molecular recurrence

  34. Assessment of correlation of molecular response depth (major molecular response i.e. BCR-ABL1<=0,1% vs. deep molecular response i.e. BCR-ABL1<=0,01%) at TKI discontinuation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of molecular response depth (major molecular response i.e. BCR-ABL1<=0,1% vs. deep molecular response i.e. BCR-ABL1<=0,01%) at TKI discontinuation with success of TFR / survival without molecular recurrence

  35. Assessment of correlation of early molecular response (BCR-ABL1 transcript levels at month 3 of TKI treatment ≤ 10% versus > 10%) with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of early molecular response (BCR-ABL1 transcript levels at month 3 of TKI treatment ≤ 10% versus > 10%) with success of TFR / survival without molecular recurrence

  36. Assessment of correlation of withdrawal syndrome with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of withdrawal syndrome (using CTCAE 5 grade classification) with success of TFR / survival without molecular recurrence

  37. Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood prior to study entry with success of TFR / survival without molecular recurrence

  38. Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood(defined below The immunological profile of patients with CML) prior to study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood(defined below The immunological profile of patients with CML) prior to study entry with success of TFR / survival without molecular recurrence

  39. Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood during TKI dose deescalation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood during TKI dose deescalation with success of TFR / survival without molecular recurrence

  40. Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood during TKI dose deescalation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood (defined below The immunological profile of patients with CML) during TKI dose deescalation with success of TFR / survival without molecular recurrence

  41. Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood after TKI discontinuation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells number in leukocyte subpopulations in peripheral blood during TKI dose deescalation with success of TFR / survival without molecular recurrence

  42. Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood after TKI discontinuation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of white blood cells activation in leukocyte subpopulations in peripheral blood (defined below The immunological profile of patients with CML) after TKI discontinuation with success of TFR / survival without molecular recurrence

  43. Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) at study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) at study entry with success of TFR / survival without molecular recurrence

  44. Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) during TKI dose deescalation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) during TKI dose deescalation with success of TFR / survival without molecular recurrence

  45. Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) after TKI discontinuation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the DNA level (gBCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) after TKI discontinuation with success of TFR / survival without molecular recurrence

  46. Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) at study entry with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) at study entry with success of TFR / survival without molecular recurrence

  47. Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) during TKI dose deescalation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) during TKI dose deescalation with success of TFR / survival without molecular recurrence

  48. Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) after TKI discontinuation with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of minimal residual disease at the mRNA level (BCR-ABL1) using digital PCR (ddPCR) (see below Quantification of minimal residual disease) after TKI discontinuation with success of TFR / survival without molecular recurrence

  49. Assessment of correlation of gene promoters' genotypes coding transmembrane imatinib transporters with success of TFR / survival without molecular recurrence [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of gene promoters' genotypes coding transmembrane imatinib transporters (genes SLC22A4, SLC22A5) (see below Genotype analysis of imatinib transmembrane transporter gene promoters) with success of TFR / survival without molecular recurrence

  50. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations - number of T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells) prior to study entry

  51. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with frequency of the withdrawal syndrome prior to study entry

  52. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with severity of the withdrawal syndrome prior to study entry

  53. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - activation) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly) prior to study entry

  54. Correlation of lymphocyte subpopulations activation in peripheral blood with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with frequency of the withdrawal syndrome prior to study entry

  55. Correlation of lymphocyte subpopulations activation in peripheral blood with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with severity of the withdrawal syndrome prior to study entry

  56. The immunological profile of patients with CML (analysis of T-cell receptor) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of T-cell receptor: TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP) prior to study entry

  57. Correlation of T-cell receptor analysis in peripheral blood with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the frequency of the withdrawal syndrome prior to study entry

  58. Correlation of T-cell receptor analysis in peripheral blood with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the frequency of the withdrawal syndrome prior to study entry

  59. The immunological profile of patients with CML (analysis of Natural Killer Cells) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange) prior to study entry

  60. Correlation of analysis of Natural Killer Cells with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the frequency of the withdrawal syndrome prior to study entry

  61. Correlation of analysis of Natural Killer Cells with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the severity of the withdrawal syndrome prior to study entry

  62. The immunological profile of patients with CML (T-ly proliferative activity) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue) prior to study entry

  63. Correlation of the T-ly proliferative activity with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the frequency of the withdrawal syndrome prior to study entry

  64. Correlation of the T-ly proliferative activity with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the severity of the withdrawal syndrome prior to study entry

  65. The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127) prior to study entry

  66. Correlation of T-regulatory-lymphocytes with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the frequency of the withdrawal syndrome prior to study entry

  67. Correlation of T-regulatory-lymphocytes with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the severity of the withdrawal syndrome prior to study entry

  68. The immunological profile of patients with CML (analysis of anti-PD1 expression) prior to study entry [ Time Frame: baseline ]
    The immunological profile of patients with CML (analysis of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange) prior to study entry

  69. Correlation of anti-PD1 expression with the frequency of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the frequency of the withdrawal syndrome prior to study entry

  70. Correlation of anti-PD1 expression with the severity of the withdrawal syndrome prior to study entry [ Time Frame: baseline ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the severity of the withdrawal syndrome prior to study entry

  71. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations - number of T-lymphocytes, CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells) during TKI dose deescalation

  72. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with frequency of the withdrawal syndrome during TKI dose deescalation

  73. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with severity of the withdrawal syndrome during TKI dose deescalation

  74. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - activation) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly) during TKI dose deescalation

  75. Correlation of lymphocyte subpopulations activation in peripheral blood with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with frequency of the withdrawal syndrome during TKI dose deescalation

  76. Correlation of lymphocyte subpopulations activation in peripheral blood with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with severity of the withdrawal syndrome during TKI dose deescalation

  77. The immunological profile of patients with CML (analysis of T-cell receptor) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of T-cell receptor: TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP) during TKI dose deescalation

  78. Correlation of T-cell receptor analysis in peripheral blood with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the frequency of the withdrawal syndrome during TKI dose deescalation

  79. Correlation of T-cell receptor analysis in peripheral blood with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the severity of the withdrawal syndrome during TKI dose deescalation

  80. The immunological profile of patients with CML (analysis of Natural Killer Cells) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange) during TKI dose deescalation

  81. Correlation of analysis of Natural Killer Cells with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the frequency of the withdrawal syndrome during TKI dose deescalation

  82. Correlation of analysis of Natural Killer Cells with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the severity of the withdrawal syndrome during TKI dose deescalation

  83. The immunological profile of patients with CML (T-ly proliferative activity) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue) during TKI dose deescalation

  84. Correlation of the T-ly proliferative activity with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the frequency of the withdrawal syndrome during TKI dose deescalation

  85. Correlation of the T-ly proliferative activity with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the severity of the withdrawal syndrome during TKI dose deescalation

  86. The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127) during TKI dose deescalation

  87. Correlation of T-regulatory-lymphocytes with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the frequency of the withdrawal syndrome during TKI dose deescalation

  88. Correlation of T-regulatory-lymphocytes with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the severity of the withdrawal syndrome during TKI dose deescalation

  89. The immunological profile of patients with CML (analysis of anti-PD1 expression) during TKI dose deescalation [ Time Frame: month 6,12 ]
    The immunological profile of patients with CML (analysis of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange) during TKI dose deescalation

  90. Correlation of anti-PD1 expression with the frequency of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the frequency of the withdrawal syndrome during TKI dose deescalation

  91. Correlation of anti-PD1 expression with the severity of the withdrawal syndrome during TKI dose deescalation [ Time Frame: month 6,12 ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the severity of the withdrawal syndrome during TKI dose deescalation

  92. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations - number of T-lymphocytes, CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells) after TKI discontinuation

  93. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with frequency of the withdrawal syndrome after TKI discontinuation

  94. Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes, B-lymphocytes, Natural-Killer-Cells number in peripheral blood with severity of the withdrawal syndrome after TKI discontinuation

  95. The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - activation) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly) after TKI discontinuation

  96. Correlation of lymphocyte subpopulations activation in peripheral blood with the frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with frequency of the withdrawal syndrome after TKI discontinuation

  97. Correlation of lymphocyte subpopulations activation in peripheral blood with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of lymphocyte subpopulations activation - CD57 T-ly/T ly; γδ T-ly/T-ly; CD4_Ki67_T-ly/CD4_T-ly; CD8_Ki67_T-ly/CD8_T-ly; CD4_HLA-DR_T-ly/CD4_T-ly; CD8_HLA-DR_T-ly/CD8_T-ly; CD4_CD62L_T-ly/CD4_T-ly; CD8_CD62L_T-ly/CD8_T-ly; CD4_CD45RA_T-ly/CD4_T-ly; CD8_CD45RA_T-ly/CD8_T-ly; CD4_CD45RO_T-ly/CD4_T-ly; CD8_CD45RO_T-ly/CD8_T-ly; PD1_CD4_T-ly; PD1_CD8_T-ly; CD107a_ CD8_T-ly with severity of the withdrawal syndrome after TKI discontinuation

  98. The immunological profile of patients with CML (analysis of T-cell receptor) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of T-cell receptor: TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP) after TKI discontinuation

  99. Correlation of T-cell receptor analysis in peripheral blood with the frequency of the withdrawal syndrome) after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the frequency of the withdrawal syndrome after TKI discontinuation

  100. Correlation of T-cell receptor analysis in peripheral blood with the severity of the withdrawal syndrome) after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of T-cell receptor analysis in peripheral blood : TCR-γ/δ PE; CD45 Pacific Orange; CD5 PE-Cy7; CD3 APC; CD8 PerCP with the severity of the withdrawal syndrome after TKI discontinuation

  101. The immunological profile of patients with CML (analysis of Natural Killer Cells) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange) after TKI discontinuation

  102. Correlation of analysis of Natural Killer Cells with the frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the frequency of the withdrawal syndrome after TKI discontinuation

  103. Correlation of analysis of Natural Killer Cells with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of analysis of Natural Killer Cells: CD57 FITC; CD16 PE; CD56 PE; CD45 PerCP; CD3 PE-Cy7; CD33 APC; CD19 Pacific Orange with the severity of the withdrawal syndrome after TKI discontinuation

  104. The immunological profile of patients with CML (T-ly proliferative activity) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue) after TKI discontinuation

  105. Correlation of the T-ly proliferative activity with the frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the frequency of the withdrawal syndrome after TKI discontinuation

  106. Correlation of the T-ly proliferative activity with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of the T-ly proliferative activity: CD4 FITC; cyKi-67 PE; HLA-DR PerCP; CD3 PE-Cy7; CD62L APC; CD8 APC-Cy7; CD107a Pacific Blue with the severity of the withdrawal syndrome after TKI discontinuation

  107. The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127) after TKI discontinuation

  108. Correlation of T-regulatory-lymphocytes with the frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the frequency of the withdrawal syndrome after TKI discontinuation

  109. Correlation of T-regulatory-lymphocytes with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of T-regulatory-lymphocytes: CD45/CD4/CD25/CD3/CD127 with the severity of the withdrawal syndrome after TKI discontinuation

  110. The immunological profile of patients with CML (analysis of anti-PD1 expression) after TKI discontinuation [ Time Frame: month 24 ]
    The immunological profile of patients with CML (analysis of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange) after TKI discontinuation

  111. Correlation of anti-PD1 expression with the frequency of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the frequency of the withdrawal syndrome after TKI discontinuation

  112. Correlation of anti-PD1 expression with the severity of the withdrawal syndrome after TKI discontinuation [ Time Frame: month 24 ]
    Correlation of anti-PD1 expression: PD-1 FITC, PD-1L PE, CD3 APC,CD4 Pacific Blue,CD8 PerCP, CD45 Pacific Orange with the severity of the withdrawal syndrome after TKI discontinuation

  113. Quantification of minimal residual disease using the highly sensitive ddPCR method at the DNA level using patient-specific BCR-ABL1 gene fusions [ Time Frame: day 0, months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Quantification of minimal residual disease using the highly sensitive ddPCR (digital polymerase chain reaction) method at the DNA level using patient-specific BCR-ABL1 gene fusions

  114. Creating a mathematic predictive model to predict TFR by the minimal residual disease (defined by the highly sensitive ddPCR method at the DNA level using patient-specific BCR-ABL1 gene fusions) [ Time Frame: day 0, months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Creating a mathematic predictive model to predict TFR by the minimal residual disease (defined by the highly sensitive ddPCR method at the DNA level using patient-specific BCR-ABL1 gene fusions)

  115. Quantification of minimal residual disease using the highly sensitive ddPCR method at BCR-ABL1 mRNA level [ Time Frame: day 0, months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Quantification of minimal residual disease using the highly sensitive ddPCR method at BCR-ABL1 mRNA (messenger RNA) level

  116. Creating a mathematic predictive model to predict TFR by the minimal residual disease (defined by the highly sensitive ddPCR method at BCR-ABL1 mRNA level) [ Time Frame: day 0, months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Creating a mathematic predictive model to predict TFR by the minimal residual disease (defined by the highly sensitive ddPCR method at BCR-ABL1 mRNA level)

  117. Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A4 [ Time Frame: baseline ]
    Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A4 (Solute carrier family 22, member 4)

  118. Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A5 [ Time Frame: baseline ]
    Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A5 (Solute carrier family 22 member 5)

  119. Creating a mathematical predictive model to predict a molecular relapse using BCR-ABL1 transcripts levels kinetics during TKI administration (see above BCR-ABL1 kinetics during TKI therapy) [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Creating a mathematical predictive model to predict a molecular relapse using BCR-ABL1 transcripts levels kinetics during TKI administration (see above BCR-ABL1 kinetics during TKI therapy)

  120. Analysis of molecular mutations within clonal hematopoiesis using NGS [ Time Frame: baseline ]
    Analysis of molecular mutations within clonal hematopoiesis using NGS (new generation sequencing) - panel of mutations of interest: ASXL1, RUNX1, TET2, DNMT3A, NRAS, TP53, JAK2, BCOR, EZH2, CBL, ZRSR2, IDH1, U2AF (PTPN11, U2AF1

  121. Assessment of correlation of molecular mutations occurrence within clonal hematopoiesis (using NGS) with TFR / molecular recurrence-free survival [ Time Frame: months 2,4,6,8,10,12,15,18,21,24,30,36 ]
    Assessment of correlation of molecular mutations occurrence within clonal hematopoiesis (using NGS) with TFR / molecular recurrence-free survival

  122. Evaluation of economic aspects of TKI dose reduction (cost benefit analysis) [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Evaluation of economic aspects of TKI dose reduction (cost benefit analysis)

  123. Evaluation of economic aspects of TKI discontinuation (cost benefit analysis) [ Time Frame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36 ]
    Evaluation of economic aspects of TKI discontinuation (cost benefit analysis)

  124. Assessing the proportion of patients entering the study out of the total number of patients meeting the study entry criteria [ Time Frame: day -28-0 ]
    Assessing the proportion of patients entering the study out of the total number of patients meeting the study entry criteria

  125. Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you have any trouble doing strenuous activities, like carrying a heavy shopping bag or a suitcase? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Do you have any trouble doing strenuous activities, like carrying a heavy shopping bag or a suitcase? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  126. Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you have any trouble taking a long walk? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Do you have any trouble taking a long walk? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  127. Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you have any trouble taking a short walk outside of the house? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Do you have any trouble taking a short walk outside of the house? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  128. Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you need to stay in bed or a chair during the day? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Do you need to stay in bed or a chair during the day? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  129. Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you need help with eating, dressing, washing yourself or using the toilet? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Do you need help with eating, dressing, washing yourself or using the toilet? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  130. Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in doing either your work or other daily activities? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Were you limited in doing either your work or other daily activities? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  131. Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in pursuing your hobbies or other leisure time activities? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Were you limited in pursuing your hobbies or other leisure time activities? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  132. Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you short of breath? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Were you short of breath? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  133. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had pain? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you had pain? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  134. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you need to rest? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did you need to rest? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  135. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had trouble sleeping? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you had trouble sleeping? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  136. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt weak? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you felt weak? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  137. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you lacked appetite? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you lacked appetite? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  138. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt nauseated? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you felt nauseated? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  139. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you vomited? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you vomited? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  140. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been constipated? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you been constipated? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  141. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had diarrhea? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you had diarrhea? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  142. Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you tired? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Were you tired? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  143. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did pain interfere with your daily activities? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did pain interfere with your daily activities? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  144. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had difficulty in concentrating on things, like reading a newspaper or watching television? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you had difficulty in concentrating on things, like reading a newspaper or watching television? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  145. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel tense? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did you feel tense? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  146. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you worry? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did you worry? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  147. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel irritable? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did you feel irritable? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  148. Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel depressed? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Did you feel depressed? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  149. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had difficulty remembering things? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Have you had difficulty remembering things? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  150. Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your family life? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Has your physical condition or medical treatment interfered with your family life? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  151. Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your social activities? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Has your physical condition or medical treatment interfered with your social activities? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  152. Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment caused you financial difficulties? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - Has your physical condition or medical treatment caused you financial difficulties? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  153. Quality of life assessment during dose de-escalation and after TKI discontinuation - How would you rate your overall health during the past week? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - How would you rate your overall health during the past week? 1 (very poor) -2-3-4-5-6-7 (excellent)

  154. Quality of life assessment during dose de-escalation and after TKI discontinuation - How would you rate your overall quality of life during the past week? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-C30) - How would you rate your overall quality of life during the past week? 1 (very poor) -2-3-4-5-6-7 (excellent)

  155. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had abdominal pains or cramps? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had abdominal pains or cramps? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  156. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had a dry mouth? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had a dry mouth? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  157. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been concerned about changes in your weight? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you been concerned about changes in your weight? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  158. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had skin problems (e.g. color changes, itchy, dry or flaking skin)? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had skin problems (e.g. color changes, itchy, dry or flaking skin)? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  159. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had headaches? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had headaches? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  160. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had aches or pains in your muscles or joints? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had aches or pains in your muscles or joints? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  161. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had hair loss? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had hair loss? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  162. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you sweated? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you sweated? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  163. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had acid indigestion or heartburn? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had acid indigestion or heartburn? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  164. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt drowsy? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you felt drowsy? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  165. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you experienced any swelling in certain parts of your body (e.g. ankles, legs or around your eyes)? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you experienced any swelling in certain parts of your body (e.g. ankles, legs or around your eyes)? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  166. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had to urinate frequently? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had to urinate frequently? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  167. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had problems with your eyes (e.g. burning, watery, irritated or dry)? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had problems with your eyes (e.g. burning, watery, irritated or dry)? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  168. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had muscle cramps? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had muscle cramps? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  169. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had emotional ups and downs? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had emotional ups and downs? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  170. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about your future health? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you worried about your future health? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  171. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had any difficulties carrying on with your usual activities because of getting tired easily? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you had any difficulties carrying on with your usual activities because of getting tired easily? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  172. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about getting an infection? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you worried about getting an infection? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  173. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt dissatisfied with your body as result of the disease or treatment? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you felt dissatisfied with your body as result of the disease or treatment? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  174. Quality of life assessment during dose de-escalation and after TKI discontinuation - How much has your treatment been a burden to you? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - How much has your treatment been a burden to you? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  175. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you needed social support (e.g. family, friends or relatives) to undergo therapy or to cope with the disease? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you needed social support (e.g. family, friends or relatives) to undergo therapy or to cope with the disease? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  176. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt satisfied with the care you have received? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you felt satisfied with the care you have received? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  177. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt satisfied with the information you have received (e.g. about the disease and its treatment)? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you felt satisfied with the information you have received (e.g. about the disease and its treatment)? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)

  178. Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt satisfied with the quality of your social life (including family and/ or friends)? [ Time Frame: day 0, month 6,12,18, 24, 36 ]
    Quality of life assessment during dose de-escalation and after TKI discontinuation (using EORTC questionnaires QLQ-CML24) - Have you felt satisfied with the quality of your social life (including family and/ or friends)? not at all (1 point) - a little (2 points) - quite a bit (3 points) - very much (4 points)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with documented Ph1-positive and / or BCR-ABL1-positive CML in a documented first chronic phase, the criteria of which are as follows:

    • <15% blasts in peripheral blood (PB) or bone marrow (BM)
    • <30% blasts + promyelocytes in PB or BM
    • <20% of basophils in PB
    • >= 100 billion / l platelets
    • Absence of extramedullary involvement except hepato- and / or splenomegaly
  2. Age >= 18 years
  3. Signed informed consent to study participation
  4. Typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale
  5. Treatment of TKI either in the first line or in the second or other lines for intolerance only
  6. TKI treatment> 4 years
  7. Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)
  8. Deep molecular response >= MR4.0 lasting > 2 years
  9. Participants in a fertile clinical trial must agree to use prescribed contraceptive methods from entry to study until one year after the last dose of study medication:

    • Women - Proper use of a highly reliable contraceptive method, ie combined hormonal contraceptives (in oral, vaginal or transdermal dosage form), gestagen hormonal contraceptives associated with ovulation inhibition (in oral or injectable dosage form), non-hormonal IUDs (intrauterine device) or IUDs , ev. presence of bilateral tubular occlusion, partner vasectomy, or adherence to sexual abstinence
    • Men - Observance of sexual abstinence or use of adequate contraceptive method (ie condom) in the case of sexual intercourse for the period from enrollment to 1 year after the last dose of the drug

Exclusion Criteria:

  1. Patients with Ph1-positive and / or BCR-ABL1-positive CML in the second chronic phase, in the accelerated phase or blast crisis (AP/BC) at any time in the history of the disease
  2. Non-quantifiable type of BCR-ABL1 transcript on an international scale
  3. Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013
  4. Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013
  5. Previous allogeneic hematopoietic stem cell transplantation
  6. Previous participation in a TKI withdrawal study with a real withdrawal history
  7. Previous discontinuation of TKI outside the study for other reasons (eg intolerance or pregnancy) lasting more than 9 months and / or if a treatment response was lost during less than 12 months prior to screening
  8. Life expectancy of less than 36 months due to severe concurrent disease
  9. Severe concurrent disease that could limit adherence to study protocol or study completion
  10. Pregnancy and breastfeeding
  11. Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04147533


Contacts
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Contact: Regina Demlova 00420 549 496526 demlova@med.muni.cz

Locations
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Czechia
University Hospital Brno
Brno, Czechia, 62500
Contact: Daniela Zackova    +420 532 232838    Zackova.Daniela@fnbrno.cz   
University Hospital Hradec Kralove
Hradec Králové, Czechia, 50005
Contact: Petra Belohlavkova    +420 495 833837    petra.belohlavkova@fnhk.cz   
University Hospital Olomouc
Olomouc, Czechia, 77900
Contact: Edgar Faber    +420 588 442877    edgar.faber@fnol.cz   
University Hospital Ostrava
Ostrava, Czechia, 70852
Contact: Lukas Stejskal    +420 597 372754    lukas.stejskal@fno.cz   
University Hospital Plzen
Plzen, Czechia, 30599
Contact: Michal Karas    +420 377 103812    KARAS@fnplzen.cz   
University Hospital Kralovske Vinohrady
Praha, Czechia, 10034
Contact: Olga Cerna    +420 267 162887    cerna@fnkv.cz   
Insitute of Hematology and Blood Transfusion
Praha, Czechia, 12800
Contact: Hana Klamova    +420 221 977277    Hana.Klamova@uhkt.cz   
General University Hospital in Prague
Praha, Czechia, 12808
Contact: Eduard Cmunt    +420 224 962526    Eduard.Cmunt@vfn.cz   
Sponsors and Collaborators
Masaryk University
Investigators
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Principal Investigator: Daniela Zackova University Hospital Brno

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Responsible Party: Masaryk University
ClinicalTrials.gov Identifier: NCT04147533    
Other Study ID Numbers: HALF2019
First Posted: November 1, 2019    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masaryk University:
tyrosine kinase inhibitors
drug withdrawal
chronic myeloid leukemia, chronic phase
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action