Back to resultsEfficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia (HALF)
Primary Purpose
Chronic Myeloid Leukemia, Chronic Phase, Withdrawal;Drug
Status
Active
Phase
Phase 2
Locations
Czechia
Study Type
Interventional
Intervention
Imatinib withdrawal
Dasatinib
Nilotinib
Sponsored by
About this trial
This is an interventional other trial for Chronic Myeloid Leukemia, Chronic Phase focused on measuring tyrosine kinase inhibitors, drug withdrawal, chronic myeloid leukemia, chronic phase
Eligibility Criteria
Inclusion Criteria:
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
- Age >= 18 years
- Signed informed consent to study participation
- Typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale
- Treatment of TKI either in the first line or in the second or other lines for intolerance only
- TKI treatment> 4 years
- Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)
- Deep molecular response >= MR4.0 lasting > 2 years
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:
- 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
- Non-quantifiable type of BCR-ABL1 transcript on an international scale
- Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013
- Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013
- Previous allogeneic hematopoietic stem cell transplantation
- Previous participation in a TKI withdrawal study with a real withdrawal history
- 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
- Life expectancy of less than 36 months due to severe concurrent disease
- Severe concurrent disease that could limit adherence to study protocol or study completion
- Pregnancy and breastfeeding
- Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria
Sites / Locations
- University Hospital Brno
- University Hospital Hradec Kralove
- University Hospital Olomouc
- University Hospital Ostrava
- University Hospital Plzen
- University Hospital Kralovske Vinohrady
- Insitute of Hematology and Blood Transfusion
- General University Hospital in Prague
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
initially treated patients
Arm Description
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.
Outcomes
Primary Outcome Measures
proportion of patients in major molecular response, and MRFS at month 6
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
proportion of patients in major molecular response (MMR) and MRFS at month 12
Proportion of patients in major molecular response (MMR) and MRFS at month 12 after study entry
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 18 after study entry, ie. 6 months after treatment withdrawal
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
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 24 after study entry, ie. 12 months after treatment withdrawal
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
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 36 after study entry, ie. 24 months after treatment withdrawal
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
Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 will recover after TKI re-introduction
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
Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction
Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction
Time to re-establish MMR and MR4.0 after TKI restart
Time to re-establish MMR and MR4.0 after TKI restart - evaluation every 3 months after TKI restart
Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal
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)
Assessment of TKI withdrawal syndrome - proportion of patients with development of withdrawal syndrome
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)
Assessment of TKI withdrawal syndrome - severity of symptoms
Assessment of TKI withdrawal syndrome - severity of symptoms (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)
Assessment of TKI withdrawal syndrome - time to first complaint
Assessment of TKI withdrawal syndrome - time to first complaint
Assessment of TKI withdrawal syndrome - duration of complaints
Assessment of TKI withdrawal syndrome - duration of complaints
Assessment of TKI withdrawal syndrome - therapeutic intervention
Assessment of TKI withdrawal syndrome - therapeutic intervention (pharmacological history, dose changes)
Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome
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)
BCR-ABL1 kinetics during TKI therapy
number of BCR-ABL1 transcripts during TKI therapy
Correlation of BCR-ABL1 kinetics (number of BCR-ABL1 transcripts in time) during TKI therapy with potential molecular relapse after TKI discontinuation
Correlation of BCR-ABL1 kinetics during TKI therapy with potential molecular relapse after TKI discontinuation
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)
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04147533
Brief Title
Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia
Acronym
HALF
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 16, 2020 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masaryk University
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia, Chronic Phase, Withdrawal;Drug
Keywords
tyrosine kinase inhibitors, drug withdrawal, chronic myeloid leukemia, chronic phase
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
initially treated patients
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Imatinib withdrawal
Other Intervention Name(s)
Glivec withdrawal
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
Sprycel withdrawal
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Other Intervention Name(s)
Tasigna withdrawal
Intervention Description
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
Primary Outcome Measure Information:
Title
proportion of patients in major molecular response, and MRFS at month 6
Description
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
Time Frame
6 months after entry
Title
proportion of patients in major molecular response (MMR) and MRFS at month 12
Description
Proportion of patients in major molecular response (MMR) and MRFS at month 12 after study entry
Time Frame
12 months after study entry
Title
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 18 after study entry, ie. 6 months after treatment withdrawal
Description
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
Time Frame
18 months after study entry
Title
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 24 after study entry, ie. 12 months after treatment withdrawal
Description
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
Time Frame
24 months after study entry
Title
proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 36 after study entry, ie. 24 months after treatment withdrawal
Description
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
Time Frame
36 months after study entry
Secondary Outcome Measure Information:
Title
Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 will recover after TKI re-introduction
Description
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
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)
Title
Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction
Description
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
Title
Time to re-establish MMR and MR4.0 after TKI restart
Description
Time to re-establish MMR and MR4.0 after TKI restart - evaluation every 3 months after TKI restart
Time Frame
since TKI restart until MMR and MR4.0 recovered (only in case that restart is necessary)
Title
Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal
Description
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)
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)
Title
Assessment of TKI withdrawal syndrome - proportion of patients with development of withdrawal syndrome
Description
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)
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
Title
Assessment of TKI withdrawal syndrome - severity of symptoms
Description
Assessment of TKI withdrawal syndrome - severity of symptoms (using Common Terminology Criteria for Adverse Events; CTCAE classification with 5 grades)
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
Title
Assessment of TKI withdrawal syndrome - time to first complaint
Description
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
Title
Assessment of TKI withdrawal syndrome - duration of complaints
Description
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
Title
Assessment of TKI withdrawal syndrome - therapeutic intervention
Description
Assessment of TKI withdrawal syndrome - therapeutic intervention (pharmacological history, dose changes)
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
Title
Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome
Description
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)
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
Title
BCR-ABL1 kinetics during TKI therapy
Description
number of BCR-ABL1 transcripts 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
Title
Correlation of BCR-ABL1 kinetics (number of BCR-ABL1 transcripts in time) during TKI therapy with potential molecular relapse after TKI discontinuation
Description
Correlation of BCR-ABL1 kinetics 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
Title
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)
Description
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
Other Pre-specified Outcome Measures:
Title
failure-free survival
Description
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
Title
progression-free survival
Description
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
Title
overall survival
Description
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
Title
Assessment of correlation of age with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of gender with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of Sokal index (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of Hasford score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of EUTOS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of ELTS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of BCR-ABL1 transcript type with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of previous interferon alfa therapy (yes/no) with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of previous interferon alfa therapy length with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of TKI type - imatinib - with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of TKI type - nilotinib - with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of TKI type - dasatinib - with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of length of imatinib therapy prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of length of dasatinib therapy prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of length of nilotinib therapy prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Plasma concentration of imatinib prior to study entry
Description
Plasma concentration of imatinib prior to study entry
Time Frame
day 0
Title
Plasma concentration of imatinib during dose deescalation period
Description
Plasma concentration of imatinib during dose deescalation period
Time Frame
month 6, 12
Title
Plasma concentration of nilotinib prior to study entry
Description
Plasma concentration of nilotinib prior to study entry
Time Frame
day 0
Title
Plasma concentration of nilotinib during dose deescalation period
Description
Plasma concentration of nilotinib during dose deescalation period
Time Frame
month 6, 12
Title
Plasma concentration of dasatinib prior to study entry
Description
Plasma concentration of dasatinib prior to study entry
Time Frame
day 0
Title
Plasma concentration of dasatinib during dose deescalation period
Description
Plasma concentration of dasatinib during dose deescalation period
Time Frame
month 6, 12
Title
Assessment of correlation of imatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of imatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of nilotinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of nilotinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of dasatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of dasatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of time needed to establish DMR after TKI start with success of TFR / survival without molecular recurrence
Description
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
Title
Assessment of correlation of deep molecular response length prior to study entry with success of TFR / survival without molecular recurrence
Description
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
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Title
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
Description
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
Title
Assessment of correlation of withdrawal syndrome with success of TFR / survival without molecular recurrence
Description
Assessment of correlation of withdrawal syndrome (using CTCAE 5 grade classification) with success of TFR / survival without molecular recurrence
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
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
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
Assessment of correlation of gene promoters' genotypes coding transmembrane imatinib transporters with success of TFR / survival without molecular recurrence
Description
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
Time Frame
months 2,4,6,8,10,12,15,18,21,24,30,36
Title
The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) prior to study entry
Description
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 (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood) prior to study entry
Time Frame
baseline
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome prior to study entry
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with frequency of the withdrawal syndrome prior to study entry
Time Frame
baseline
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome prior to study entry
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with severity of the withdrawal syndrome prior to study entry
Time Frame
baseline
Title
The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) during TKI dose deescalation
Description
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 (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood) during TKI dose deescalation
Time Frame
month 6,12
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome during TKI dose deescalation
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with frequency of the withdrawal syndrome during TKI dose deescalation
Time Frame
month 6,12
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome during TKI dose deescalation
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with severity of the withdrawal syndrome during TKI dose deescalation
Time Frame
month 6,12
Title
The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) after TKI discontinuation
Description
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 (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood) after TKI discontinuation
Time Frame
month 24
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome after TKI discontinuation
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with frequency of the withdrawal syndrome after TKI discontinuation
Time Frame
month 24
Title
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with the severity of the withdrawal syndrome after TKI discontinuation
Description
Correlation of characteristics of lymphocyte subpopulations in peripheral blood - T-lymphocytes (T-ly), CD4-T-lymphocytes, CD8T-lymphocytes, T-regulatory-lymphocytes (CD 3+4+25+127-), B-lymphocytes, Natural-Killer-Cells number, myeloid-derived suppressor cells in peripheral blood with severity of the withdrawal syndrome after TKI discontinuation
Time Frame
month 24
Title
Quantification of minimal residual disease using the highly sensitive ddPCR method at the DNA level using patient-specific BCR-ABL1 gene fusions
Description
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
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
Title
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)
Description
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
Title
Quantification of minimal residual disease using the highly sensitive ddPCR method at BCR-ABL1 mRNA level
Description
Quantification of minimal residual disease using the highly sensitive ddPCR method at BCR-ABL1 mRNA (messenger RNA) 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
Title
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)
Description
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
Title
Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A4
Description
Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A4 (Solute carrier family 22, member 4)
Time Frame
baseline
Title
Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A5
Description
Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A5 (Solute carrier family 22 member 5)
Time Frame
baseline
Title
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)
Description
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
Title
Analysis of molecular mutations within clonal hematopoiesis using NGS
Description
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
Time Frame
baseline
Title
Assessment of correlation of molecular mutations occurrence within clonal hematopoiesis (using NGS) with TFR / molecular recurrence-free survival
Description
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
Title
Evaluation of economic aspects of TKI dose reduction (cost benefit analysis)
Description
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
Title
Evaluation of economic aspects of TKI discontinuation (cost benefit analysis)
Description
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
Title
Assessing the proportion of patients entering the study out of the total number of patients meeting the study entry criteria
Description
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
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you have any trouble taking a long walk?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in doing either your work or other daily activities?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in pursuing your hobbies or other leisure time activities?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you short of breath?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had pain?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you need to rest?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had trouble sleeping?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt weak?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you lacked appetite?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt nauseated?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you vomited?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been constipated?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had diarrhea?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you tired?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did pain interfere with your daily activities?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel tense?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you worry?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel irritable?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel depressed?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had difficulty remembering things?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your family life?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your social activities?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment caused you financial difficulties?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - How would you rate your overall health during the past week?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had abdominal pains or cramps?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had a dry mouth?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been concerned about changes in your weight?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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)?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had headaches?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had aches or pains in your muscles or joints?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had hair loss?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you sweated?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had acid indigestion or heartburn?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt drowsy?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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)?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had to urinate frequently?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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)?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had muscle cramps?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had emotional ups and downs?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about your future health?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about getting an infection?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - How much has your treatment been a burden to you?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt satisfied with the care you have received?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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)?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
Title
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)?
Description
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)
Time Frame
day 0, month 6,12,18, 24, 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Age >= 18 years
Signed informed consent to study participation
Typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale
Treatment of TKI either in the first line or in the second or other lines for intolerance only
TKI treatment> 4 years
Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)
Deep molecular response >= MR4.0 lasting > 2 years
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:
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
Non-quantifiable type of BCR-ABL1 transcript on an international scale
Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013
Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013
Previous allogeneic hematopoietic stem cell transplantation
Previous participation in a TKI withdrawal study with a real withdrawal history
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
Life expectancy of less than 36 months due to severe concurrent disease
Severe concurrent disease that could limit adherence to study protocol or study completion
Pregnancy and breastfeeding
Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniela Zackova
Organizational Affiliation
University Hospital Brno
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Brno
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
University Hospital Hradec Kralove
City
Hradec Králové
ZIP/Postal Code
50005
Country
Czechia
Facility Name
University Hospital Olomouc
City
Olomouc
ZIP/Postal Code
77900
Country
Czechia
Facility Name
University Hospital Ostrava
City
Ostrava
ZIP/Postal Code
70852
Country
Czechia
Facility Name
University Hospital Plzen
City
Plzen
ZIP/Postal Code
30599
Country
Czechia
Facility Name
University Hospital Kralovske Vinohrady
City
Praha
ZIP/Postal Code
10034
Country
Czechia
Facility Name
Insitute of Hematology and Blood Transfusion
City
Praha
ZIP/Postal Code
12800
Country
Czechia
Facility Name
General University Hospital in Prague
City
Praha
ZIP/Postal Code
12808
Country
Czechia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients With Chronic Myeloid Leukemia
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