Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML) and is the current standard of care in the treatment of patients with newly diagnosed CML. However, about 30% of patients still show drug resistance or disease progression. Currently, the most widely studied mechanism of TKI resistance in CML patients is mutations in the ABL kinase region. So far, more than 100 kinase domain mutations have been found in disease progression and imatinib resistance. It is estimated that more than 25% of CML patients will change TKI at least once in their lifetime due to drug resistance or intolerance. The 2020 edition of the "Guidelines for the Diagnosis and Treatment of Chronic Myelogenous Leukemia in China" proposes that patients with F317L/V/I/C, V299L and T315A mutations are more likely to obtain clinical efficacy by switching to the second-generation TKI nilotinib; patients with Y253H, E255K/V and F359C/V/I mutations are more likely to obtain clinical efficacy by switching to the second-generation TKI dasatinib; patients with T315I mutations are resistant to both nilotinib and dasatinib. Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. In vitro studies, it has shown that flumatinib inhibits wild-type and common BCR-ABL mutations(Q252H, V299L, F317L/I, M351T, H396P, etc.) more potently, and the anti-mutation spectrum of flumatinib is similar to nilotinib. Therefore, this study is designed to provide clearer guidance for patients with specific BCR-ABL kinase point mutations during CML treatment.

NCT04681820

Conditions

1. CML-CP; Mutation;TKI

Interventions

1. Drug: Flumatinib
2. Drug: Nilotinib

MeSH:Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myelo Leukemia, Myeloid, Chronic-Phase

HPO:Chronic myelogenous leukemia

Inclusion Criteria: 1. Male or female patients ≥18 years of age; 2. CML-CP patients when enrolled Definition of diagnosis: Bone marrow cytogenetic confirmation of Philadelphia chromosome of t (9;22) translocations and/or the presence of P210 BCR-ABL1 transcripts via molecular assessment; Documented chronic phase CML will meet all the criteria defined as: < 15% blasts in peripheral blood and bone marrow < 30% blasts plus promyelocytes in peripheral blood and bone marrow < 20% basophils in the peripheral blood ≥ 100 x 109/L (≥ 100,000/mm3) platelets No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly 3. Specific BCR-ABL1 kinase mutations sensitive to flumatinib (including F317L/I, M351T, Q252H, M244V, V299L, F311L, H396R, E355G, L387M) were found in patients with poor response to imatinib or dasatinib treatment, treatment failure, disease progression, MMR but not DMR or unstable DMR. 4. Female patients of childbearing potential must have a negative serum pregnancy test; 5. Ability to provide written informed consent prior to any study related screening procedures being performed. --- F317L --- --- M351T --- --- Q252H --- --- M244V --- --- V299L --- --- F311L --- --- H396R --- --- E355G --- --- L387M ---