MedDRA version: 21.1 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: IMATINIB
Product Name: IMATINIB
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib
CAS Number: 152459-95-5
INN or Proposed INN: Imatinib mesilate
CAS Number: 220127-57-1
Trade Name
Sponsors
CHU de Poitiers
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient aged = 18 years - Diagnosed with chronic phase CML (CML-CP) according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2 or e14a2) - Duration of TKI treatment = 3 years and not having had a dose reduction in the last 6 months - Duration of DMR (= 4-log reduction in peripheral blood BCR::ABL1 mRNA level from diagnosis) = 1 year with at least 3 quantitative BCR::ABL1 mRNA RT-PCR results available in the 12 months prior to inclusion - No contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations7 and the originator's CPR of each TKI i.e.: Glivec® or generic: Imatinib (= 200 mg/d) Sprycel® or generic: Dasatinib (= 50 mg/d) Tasigna®: Nilotinib (= 300 mg/d) Bosulif®: Bosutinib (= 200 mg/d) - Sexually active men should use contraception while taking Dasatinib - Must be affiliated to the social security system or have a third party who does so - Patient not participating in another interventional study for the duration of the study - Have signed the consent form after having read the information note Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: - Patients with a serious progressive disease with poor prognosis compromising participation in the entire study and/or with an uncontrolled chronic disease (cardiac, (recent myocardial infarction, congestive heart failure, unstable angina...), renal, respiratory...) - ECOG > 3 - No previous resistance to a TKI - Patients who have already participated in a study involving a TKI discontinuation strategy - Persons benefiting from enhanced protection, i.e. minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social establishment, adults under legal protection and finally patients in emergency situations - Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception (hormonal/mechanical: per os, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total oophorectomy)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare 2 TKI discontinuation strategies on the probability of successful discontinuation in patients followed for CML treated with TKIs.;Secondary Objective: 1.2-Comparison of TKI tolerability and quality of life in 2 arms 3.4-Comparison of the proportion to loose MMR and DMR in 2 arms 5-Comparison of the quantitative and qualitative evolution of CD8i LT in 2 arms 6-Evaluate residual plasma TKI concentration for 2 arms 7-Comparison of the proportion of loss DMR during the discontinuation phase in 2 arms 8-Evaluate quality of life in the discontinuation phase in 2 arms 9-Describe for patients losing their DMR in the TKI phase and for patients losing their MMR during the discontinuation phase 10-Evaluate the predictive value at the time of discontinuation of the quantitative and qualitative characteristics of CD8LTi on the successful discontinuation between in TFR 24M post discontinuation and those who lost their MMR and resumed their TKI during the same period in 2 arms 11-Analyse longitudinally the quantitative and qualitative evolution of CD8ILT after TKI discontinuation in patients in FIT 24M post discontinuation in 2 arms ;Primary end point(s): Proportion (%) of patients in TFR 24 months after discontinuation in the dose maintenance then discontinuation arm and in the dose de-escalation then discontinuation arm.;Timepoint(s) of evaluation of this end point: 24 months after discontinuation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Recording of adverse events and scoring according to CTCAE V5 grades 2.8-Collection of EQ-5D5 and FACT-Leu32 3-Proportion (%) of patients losing their MMR 4.7-Proportion (%) of patients losing their DMR 5-Quantitative analysis: difference in the proportions, at randomisation and 12 months post-randomisation, of innate CD8 LTs within total CD8 LTs 6-Evaluation of the residual plasma concentration of the TKI in ng/mL 9-After loss of DMR during the treatment phase: collection of the prescribed TKI and its daily dosage (mg per day) as well as the time (in months) between the loss of DMR and its re-obtainment; after loss of MMR during the discontinuation phase: collection of the time (in months) between the loss of MMR and its re-obtainment 10- Quantitative analysis: proportions of CD8i LTs in total CD8 LTs 11- Quantitative analysis: proportions of innate CD8 LTs in total CD8 LTs ;Timepoint(s) of evaluation of this end point: 1-At 6 months and 12 months post-randomisation 2.8-At randomisation, 6 months and 12 months post-randomisation and at 3 months and 6 months post-stop 3-Every 3 months in both arms during the ITK treatment phase 4.7-Every 3 months in the 2 arms during the ITK treatment phase then every month until the 6th month post-stop, then every 2 months between 6 months and 12 months, then every 3 months. 5-At randomisation and 12 months post-randomisation 6-At the time of randomisation and 12 months later 9-After loss of MMR and recording of the time (in months) between the loss of MMR and its re-obtainment after resumption of TKI treatment 10-At the time of arrest 11-At the time of arrest | — |
Countries
France
Contacts
Public ContactFanny ABRIAT
CHU de Poitiers
Outcome results
None listed