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Evaluating Efficacy and Safety of Flumatinib Versus Nilotinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) With Defined BCR-ABL1 Kinase Mutations in Imatinib or Dasatinib (FINESTdm)

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ClinicalTrials.gov Identifier: NCT04681820
Recruitment Status : Recruiting
First Posted : December 23, 2020
Last Update Posted : December 23, 2020
Sponsor:
Information provided by (Responsible Party):
Weiming Li, Wuhan Union Hospital, China

Brief Summary:
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.

Condition or disease Intervention/treatment
CML-CP; Mutation;TKI Drug: Flumatinib Drug: Nilotinib

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluating Efficacy and Safety of Flumatinib Versus Nilotinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) With Defined BCR-ABL1 Kinase Mutations in Imatinib or Dasatinib: A Prospective, Multicenter, Pragmatic Clinical Trial(FINESTdm)
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : November 2024


Group/Cohort Intervention/treatment
flumatinib
flumatinib 600mg QD, fasting administration
Drug: Flumatinib
Flumatinib mesylate tablets 600mg qd for 24 months

Drug: Nilotinib
Nilotinib Capsules 400mg bid for 24 months

nilotinib
nilotinib 400mg BID, fasting administration
Drug: Flumatinib
Flumatinib mesylate tablets 600mg qd for 24 months

Drug: Nilotinib
Nilotinib Capsules 400mg bid for 24 months




Primary Outcome Measures :
  1. Major molecular response rate at 12 months [ Time Frame: 12 months ]
    Major molecular response is defined as ≤ 0.1% BCR-ABL/ABL% by international scale



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
CML-CP patients with specific BCR-ABL1 kinase mutations treated with imatinib or dasatinib
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. 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.

Exclusion Criteria:

  1. Treatment with other tyrosine kinase inhibitor(s) except imatinib and dasatinib prior to study entry;
  2. Complex mutations (except that all mutations are sensitive to flumatinib);
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04681820


Contacts
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Contact: Weiming Li 13098815546 liweiming202012@163.com

Locations
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China, Hubei
Weiming Li Recruiting
Wuhan, Hubei, China
Contact: Ming Wei Li    13098815546    liweiming202012@163.com   
Sponsors and Collaborators
Wuhan Union Hospital, China
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Responsible Party: Weiming Li, chief physician, Wuhan Union Hospital, China
ClinicalTrials.gov Identifier: NCT04681820    
Other Study ID Numbers: HS-2020-07WH
First Posted: December 23, 2020    Key Record Dates
Last Update Posted: December 23, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
HH-GV-678
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action