Evaluating Efficacy and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning,Failure) to Imatinib or Dasatinib

Study Purpose

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 suboptimal response or failure in the treatment of TKI as well as those who have specific ABL kinase domain mutations during CML treatment.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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. CML-CP patients without optimal response(warning or failure) when treated with imatinib or dasatinib. 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.

Exclusion Criteria:

1. Treatment with other tyrosine kinase inhibitor(s) except imatinib and dasatinib prior to study entry; 2. With any mutations as follows :T315I、Y253F/H、E255K/V、F359C/V/I (if there are any other mutations,at physicians' discretion ); 3. Entry into another therapeutic clinical trial; 4. Concomitant diseases that, according to the investigator's judgment, pose a serious risk to the patient's safety or completion of the study; 5. History of neurological or psychiatric disorders, including epilepsy or dementia; 6. Major surgery within 4 weeks prior to Day 1 of study; 7. Patients with another primary malignancy,unless the other primary malignancy is currently stable or does not need active intervention; 8. Women of reproductive age or men who are unable to use adequate methods of contraception, including women who are pregnant or breastfeeding; 9. ECOG≥3; 10. Patients who are unable to compliance with study or follow-up procedures; 11. Allergic to any of the components in this trial; 12. Not appropriate to attend this trial judged by the investigator.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04681820
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Wuhan Union Hospital, China
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	CML-CP; Mutation;Suboptimal Response or Failure in TKI

Arms & Interventions

Arms

: flumatinib

flumatinib 600mg QD, fasting administration

: nilotinib

nilotinib 400mg BID, fasting administration

Interventions

Drug: - Flumatinib

Flumatinib mesylate tablets 600mg qd for 24 months

Drug: - Nilotinib

Nilotinib Capsules 400mg bid for 24 months

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Weiming Li, Wuhan, Hubei, China

Status

Recruiting

Address

Weiming Li

Wuhan, Hubei,

Site Contact

Ming Wei Li

[email protected]

13098815546

Site by: Kaleidoscopic

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