2nd or 3rd TKI-stop After 2 Years Nilotinib Pre-treatment in CML-patients

The proposal is to re-treat patients with a minimum of two years with nilotinib 2x300 mg/d resulting in total of at least three years TKI treatment who show recurrent disease after unsuccessful first or second stop after TKI treatment in or outside the EURO-SKI study. If MR4 or better is re-achieved and maintained for at least one year and MR4.5 or better is re-achieved and maintained for at least 6 months, patients will be eligible for a second stop attempt within this study. For MR4, three consecutive PCRs with MR4 or deeper should be measured within one year and for MR4.5, two PCRs during 6 months should demonstrate a MR4.5. Patients who exhibited hematological relapse after the first stop attempt will not be eligible for a second stop attempt within this study. After inclusion, 3 monthly monitoring will be performed under nilotinib treatment within the trial. Patients fulfilling the criteria mentioned above will then enter the screening phase. After verification of MR4.5, TKI treatment will be stopped and patients followed in the same manner as described in EURO-SKI (monthly PCRs for 6 months, 6-weekly PCRs 7-12 months after stopping, thereafter 3-monthly). If MMR is lost (BCR-ABL \>0.1% (IS)), TKI treatment will once again be restarted; here the same TKI (nilotinib) is recommended. It is assumed that after failure of first (or second) stop a switch to treatment with 2GTKI may increase the chance of stopping a second (or third) time \[Legros et al. Blood 2012; Rea et al. Blood 2014\] It is expected that the rate of a successful second (or third) stop at 12 and 36 months is more than 25%.