Combination Study of Pioglitazone and Tyrosine Kinase Inhibitors (TKIs) in Chronic Myeloid Leukemia Patients After Failure of a First TKIs Discontinuation Attempt in Order to Prepare a New Stop
Single-center study, prospective, phase II trial. The study objectives are : * To assess safety and pharmacokinetics of the combination of PIO and TKI in CML subjects who experience a loss of MMR following a first TKI discontinuation. * To assess survival without loss of MMR over a 12 months period following a second TKI discontinuation in subjects who achieve or maintain \< MR4.5 with the combination PIO and TKI administered for at least 6 months.
• CML in any phase. patient in MR4
• Loss of MMR following a first or subsequent TKI discontinuation trial.
• Patient prior treated with imatinib, dasatinib, nilotinib, or bosutinib
• Age \>18 years.
• Serum bilirubin \<1.5 x upper limit of normal values.
• AST (SGOT)/ALT (SGPT) \<2.5x upper limit of normal values.
• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device, transdermal/implanted or injected contraceptives and abstinence.
• Males must agree to abstain from sexual activity or agree to utilize a medically-approved contraception method during and for 3 months after the treatment period.
• Signed informed consent.
⁃ Be able and willing to comply with study visits and procedures