Clinical trial NCT04147533: Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia, Chronic Phase
Withdrawal;Drug
Keywords: tyrosine kinase inhibitors
drug withdrawal
chronic myeloid leukemia, chronic phase
Lead sponsor: Masaryk University
Sponsor class: OTHER
First posted: 2019-11-01
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility 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

Primary outcomes:
measure: proportion of patients in major molecular response, and MRFS at month 6
timeFrame: 6 months after entry
measure: proportion of patients in major molecular response (MMR) and MRFS at month 12
timeFrame: 12 months after study entry
measure: proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 18 after study entry, ie. 6 months after treatment withdrawal
timeFrame: 18 months after study entry
measure: proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 24 after study entry, ie. 12 months after treatment withdrawal
timeFrame: 24 months after study entry
measure: proportion of patients in MMR without treatment (TFR) and treatment-free survival at month 36 after study entry, ie. 24 months after treatment withdrawal
timeFrame: 36 months after study entry
Secondary outcomes:
measure: Proportion of patients who lose MMR during de-escalation and in whom MMR and MR4.0 will recover after TKI re-introduction
timeFrame: 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)
measure: Proportion of patients who lose MMR after discontinuation of TKI and in whom MMR and MR4.0 will recover after TKI re-introduction
timeFrame: 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
measure: Time to re-establish MMR and MR4.0 after TKI restart
timeFrame: since TKI restart until MMR and MR4.0 recovered (only in case that restart is necessary)
measure: Assessment of TKI's adverse effects dynamics during two-step reduction of their dose before withdrawal
timeFrame: 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)
measure: Assessment of TKI withdrawal syndrome - proportion of patients with development of withdrawal syndrome
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of TKI withdrawal syndrome - severity of symptoms
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of TKI withdrawal syndrome - time to first complaint
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of TKI withdrawal syndrome - duration of complaints
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of TKI withdrawal syndrome - therapeutic intervention
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of the correlation between adverse effects on previous TKI treatment and possible withdrawal syndrome
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: BCR-ABL1 kinetics during TKI therapy
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Correlation of BCR-ABL1 kinetics (number of BCR-ABL1 transcripts in time) during TKI therapy with potential molecular relapse after TKI discontinuation
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: 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)
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
Other outcomes:
measure: failure-free survival
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: progression-free survival
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: overall survival
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessment of correlation of age with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of gender with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of Sokal index (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of Hasford score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of EUTOS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of ELTS score (calculated in time of diagnosis; if available) with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of BCR-ABL1 transcript type with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of previous interferon alfa therapy (yes/no) with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of previous interferon alfa therapy length with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of TKI type - imatinib - with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of TKI type - nilotinib - with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of TKI type - dasatinib - with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of length of imatinib therapy prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of length of dasatinib therapy prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of length of nilotinib therapy prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Plasma concentration of imatinib prior to study entry
timeFrame: day 0
measure: Plasma concentration of imatinib during dose deescalation period
timeFrame: month 6, 12
measure: Plasma concentration of nilotinib prior to study entry
timeFrame: day 0
measure: Plasma concentration of nilotinib during dose deescalation period
timeFrame: month 6, 12
measure: Plasma concentration of dasatinib prior to study entry
timeFrame: day 0
measure: Plasma concentration of dasatinib during dose deescalation period
timeFrame: month 6, 12
measure: Assessment of correlation of imatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of imatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of nilotinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of nilotinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of dasatinib plasma concentration prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of dasatinib plasma concentration during dose deescalation period with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of time needed to establish DMR after TKI start with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of deep molecular response length prior to study entry with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of withdrawal syndrome with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: 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
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Assessment of correlation of gene promoters' genotypes coding transmembrane imatinib transporters with success of TFR / survival without molecular recurrence
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) prior to study entry
timeFrame: baseline
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome prior to study entry
timeFrame: baseline
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome prior to study entry
timeFrame: baseline
measure: The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) during TKI dose deescalation
timeFrame: month 6,12
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome during TKI dose deescalation
timeFrame: month 6,12
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with severity of the withdrawal syndrome during TKI dose deescalation
timeFrame: month 6,12
measure: The immunological profile of patients with CML (characteristics of lymphocyte subpopulations in peripheral blood - cells number) after TKI discontinuation
timeFrame: month 24
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with frequency of the withdrawal syndrome after TKI discontinuation
timeFrame: month 24
measure: Correlation of characteristics of lymphocyte subpopulations in peripheral blood - cells number in peripheral blood with the severity of the withdrawal syndrome after TKI discontinuation
timeFrame: month 24
measure: Quantification of minimal residual disease using the highly sensitive ddPCR method at the DNA level using patient-specific BCR-ABL1 gene fusions
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Quantification of minimal residual disease using the highly sensitive ddPCR method at BCR-ABL1 mRNA level
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A4
timeFrame: baseline
measure: Genotype analysis of imatinib transmembrane transporter gene promoters SLC22A5
timeFrame: baseline
measure: 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)
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Analysis of molecular mutations within clonal hematopoiesis using NGS
timeFrame: baseline
measure: Assessment of correlation of molecular mutations occurrence within clonal hematopoiesis (using NGS) with TFR / molecular recurrence-free survival
timeFrame: months 2,4,6,8,10,12,15,18,21,24,30,36
measure: Evaluation of economic aspects of TKI dose reduction (cost benefit analysis)
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Evaluation of economic aspects of TKI discontinuation (cost benefit analysis)
timeFrame: months 2,4,6,8,10,12,13,14,15,16,17,18,19.5,21,22.5,24,27,30,33,36
measure: Assessing the proportion of patients entering the study out of the total number of patients meeting the study entry criteria
timeFrame: day -28-0
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Do you have any trouble taking a long walk?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in doing either your work or other daily activities?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you limited in pursuing your hobbies or other leisure time activities?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you short of breath?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had pain?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you need to rest?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had trouble sleeping?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt weak?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you lacked appetite?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt nauseated?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you vomited?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been constipated?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had diarrhea?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Were you tired?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did pain interfere with your daily activities?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel tense?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you worry?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel irritable?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Did you feel depressed?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had difficulty remembering things?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your family life?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment interfered with your social activities?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Has your physical condition or medical treatment caused you financial difficulties?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - How would you rate your overall health during the past week?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had abdominal pains or cramps?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had a dry mouth?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you been concerned about changes in your weight?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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)?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had headaches?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had aches or pains in your muscles or joints?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had hair loss?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you sweated?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had acid indigestion or heartburn?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt drowsy?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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)?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had to urinate frequently?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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)?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had muscle cramps?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you had emotional ups and downs?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about your future health?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you worried about getting an infection?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - How much has your treatment been a burden to you?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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?
timeFrame: day 0, month 6,12,18, 24, 36
measure: Quality of life assessment during dose de-escalation and after TKI discontinuation - Have you felt satisfied with the care you have received?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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)?
timeFrame: day 0, month 6,12,18, 24, 36
measure: 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)?
timeFrame: day 0, month 6,12,18, 24, 36
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Kralove
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Plzen
country: Czechia
facility: University Hospital Plzen
city: Praha
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: Insitute of Hematology and Blood Transfusion
city: Praha
country: Czechia
facility: General University Hospital in Prague
Study officials:
affiliation: University Hospital Brno
name: Daniela Zackova
role: PRINCIPAL_INVESTIGATOR
References: