Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

Prior treatment

• Previous failure of TKI treatment according to ELN criteria of 2006, 2009 or 2013
• Previous allogeneic hematopoietic stem cell transplantation
• Previous participation in a TKI withdrawal study with a real withdrawal history
• 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
• Life expectancy of less than 36 months due to severe concurrent disease
• Severe concurrent disease that could limit adherence to study protocol or study completion

Other illness

• 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
• Treatment of TKI in the second or subsequent lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013

Other

• Non-quantifiable type of BCR-ABL1 transcript on an international scale
• Pregnancy and breastfeeding
• Disagreement or impossibility to comply with the contraceptive measures described in point 9 of the inclusion criteria

• 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
• Age \>= 18 years
• Signed informed consent to study participation
• Typical \[e13a2 (b2a2) or e14a2 (b3a2)\] or atypical quantifiable type of BCR-ABL1 transcript on an international scale
• Treatment of TKI either in the first line or in the second or other lines for intolerance only
• TKI treatment\> 4 years
• Previous interferon-α treatment allowed with any treatment effect (intolerance / failure)
• Deep molecular response \>= MR4.0 lasting \> 2 years
• 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