Dasatinib for Chronic myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Patient aged ≥ 18 years\n- Diagnosed with chronic phase CML (CML-CP) according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2/b2a2 or e14a2/b3a2)\n- Duration Imatinib ≥ 4 years/ TKI2G ≥ 3 years / Imatinib + ITK2G ≥ 4 years and not having had a dose reduction in the last 6 months\n- Duration of DMR (≥ 4-log reduction in peripheral blood BCR::ABL1 mRNA level from diagnosis) ≥ 1 year\n- No contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations and the originator's CPR of each TKI i.e.: Glivec® or generic: Imatinib (≥ 300 mg/d) Sprycel® or generic: Dasatinib (≥ 50 mg/d) Tasigna®: Nilotinib (≥ 300 mg/d) Bosulif®: Bosutinib (≥ 200 mg/d)\n- Sexually active men should use contraception while taking Dasatinib\n- Must be affiliated to the social security system or have a third party who does so\n- Patient not participating in another interventional study for the duration of the study\n- Have signed the consent form after having read the information note"}

Exclusion criteria

• {"criterion_text":"- 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...)\n- ECOG > 3\n- Previous resistance to a TKI\n- Patients who have already involving a TKI discontinuation strategy\n- Patients with a malignant tumour that has been treated with chemotherapy in the 2 months prior to inclusion or is currently undergoing chemotherapy or will be treated with chemotherapy after inclusion\n- 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\n- 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)\n- Patients who lost their DMR at the inclusion visit (i.e. BCR::ABL1/ABL1 ratio > 0.01%)"}

Primary endpoints

• {"endpoint_text":"- Proportion (%) of patients in TFR 24 months after discontinuation in the dose maintenance then discontinuation arm and in the dose deescalation then discontinuation arm.","definition_or_measurement_approach":"Proportion (%) of patients in treatment-free remission (TFR) at 24 months after TKI discontinuation (measured as the percent of randomized patients meeting TFR criteria at 24 months post-discontinuation)."}

Secondary endpoints

• {"endpoint_text":"- 1-Recording of adverse events and scoring according to CTCAE V5 grades","definition_or_measurement_approach":"Adverse events recorded and graded according to CTCAE v5."}
• {"endpoint_text":"- 2.8-Collection of EQ-5D5 and FACT-Leu32","definition_or_measurement_approach":"Collection of quality-of-life instruments EQ-5D-5L and FACT-Leu32 as specified."}
• {"endpoint_text":"- 3-Proportion (%) of patients losing their MMR","definition_or_measurement_approach":"Proportion (%) of patients who lose major molecular response (MMR) during the study period."}
• {"endpoint_text":"- 4.7-Proportion (%) of patients losing their DMR","definition_or_measurement_approach":"Proportion (%) of patients who lose deep molecular response (DMR) during the study period."}
• {"endpoint_text":"- 5-Quantitative analysis: difference in the proportions, at randomisation and 12 months post-randomisation, of innate CD8 LTs within total CD8 LTs","definition_or_measurement_approach":"Quantitative comparison of proportions of innate CD8 lymphocyte types within total CD8 cells at randomisation and at 12 months post-randomisation."}
• {"endpoint_text":"- 6-Evaluation of the residual plasma concentration of the TKI in ng/mL","definition_or_measurement_approach":"Measurement of residual plasma TKI concentration reported in ng/mL."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Collection of TKI identity and daily dose (mg/day) and time (months) to re-obtainment of response after loss of DMR or MMR."}
• {"endpoint_text":"- 10- Quantitative analysis: proportions of CD8i LTs in total CD8 LTs","definition_or_measurement_approach":"Quantitative measurement of proportions of CD8i lymphocyte types within total CD8 cells."}
• {"endpoint_text":"- 11- Quantitative analysis: proportions of innate CD8 LTs in total CD8 LTs","definition_or_measurement_approach":"Quantitative measurement of proportions of innate CD8 lymphocyte types within total CD8 cells."}

France

Earliest CTIS Part Ii Submission Date

13-08-2024

Latest Decision Or Authorization Date

07-03-2025

Processing Time Days

206

Number Of Sites

20

Number Of Participants

170

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Poitiers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France