CML-CP; Mutation;Suboptimal Response or Failure in TKINCT04681820
Evaluating Efficacy and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning,Failure) to Imatinib or Dasatinib
An observational study of CML-CP; Mutation;Suboptimal Response or Failure in TKI, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CML-CP; Mutation;Suboptimal Response or Failure in TKI
- What is being tested?
- Flumatinib and Nilotinib
- Type of treatment
- Pill or oral medicine
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to Nov 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: CML-CP patients without optimal response(warning or failure) treated with imatinib or dasatinib
Who may be able to join
- Male or female patients ≥18 years of age;
- 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
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- ≥ 100 x 109/L (≥ 100,000/mm3) platelets No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- CML-CP patients without optimal response(warning or failure) when treated with imatinib or dasatinib.
- Female patients of childbearing potential must have a negative serum pregnancy test;
- Ability to provide written informed consent prior to any study related screening procedures being performed.
Who cannot join
- Treatment with other tyrosine kinase inhibitor(s) except imatinib and dasatinib prior to study entry;
- With any mutations as follows :T315I、Y253F/H、E255K/V、F359C/V/I (if there are any other mutations,at physicians' discretion );
- Entry into another therapeutic clinical trial;
- Concomitant diseases that, according to the investigator's judgment, pose a serious risk to the patient's safety or completion of the study;
- History of neurological or psychiatric disorders, including epilepsy or dementia;
- Major surgery within 4 weeks prior to Day 1 of study;
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- Patients with another primary malignancy,unless the other primary malignancy is currently stable or does not need active intervention;
- Women of reproductive age or men who are unable to use adequate methods of contraception, including women who are pregnant or breastfeeding;
- ECOG≥3;
- Patients who are unable to compliance with study or follow-up procedures;
- Allergic to any of the components in this trial;
- Not appropriate to attend this trial judged by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Weiming Li
Wuhan, Hubei
Ming Wei Li, 13098815546, liweiming202012@163.com
About this study
Official title: Evaluating Efficacy and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning or Failure) to Imatinib or Dasatinib: A Prospective, Multicenter, Pragmatic Clinical Trial
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.
- Being tested
- Flumatinib, Nilotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlumatinibDrug
Flumatinib mesylate tablets 600mg qd for 24 months
NilotinibDrug
Nilotinib Capsules 400mg bid for 24 months
| Study group | Role | What they receive |
|---|---|---|
| flumatinib | flumatinib 600mg QD, fasting administration Receives: Drug: Flumatinib; Drug: Nilotinib | |
| nilotinib | nilotinib 400mg BID, fasting administration Receives: Drug: Flumatinib; Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major molecular response rate at 12 months
Major molecular response is defined as ≤ 0.1% BCR-ABL/ABL% by international scale
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start1 Nov 2020
- Primary completionDec 2023 (estimated)
- Study completionNov 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CML-CP; Mutation;Suboptimal Response or Failure in TKIStudies of the same condition, open and under way.
- More trials run by Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Weiming Li, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04681820
- Sponsor's protocol ID
- HS-2020-07WH
- Status last verified
- Jul 2023
- First submitted
- 18 Dec 2020
- Last updated
- 1 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Efficacy and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning or Failure) to Imatinib or Dasatinib: A Prospective, Multicenter, Pragmatic Clinical Trial
- ClinicalTrials.gov ID
- NCT04681820
- Acronym / sponsor ID
- HS-2020-07WH
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Nov 2024 (estimated)
- First posted
- 23 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| flumatinib | – | Drug: Flumatinib, Drug: Nilotinibflumatinib 600mg QD, fasting administration |
| nilotinib | – | Drug: Flumatinib, Drug: Nilotinibnilotinib 400mg BID, fasting administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- CML-CP patients without optimal response(warning or failure) treated with imatinib or dasatinib
Key inclusion criteria (10 listed)
- Male or female patients ≥18 years of age;
- CML-CP patients when enrolled
- Bone marrow cytogenetic confirmation of Philadelphia chromosome of t (9;22) translocations and/or the presence of P210 BCR-ABL1 transcripts via molecular assessment;
- < 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
Key exclusion criteria (12 listed)
- Treatment with other tyrosine kinase inhibitor(s) except imatinib and dasatinib prior to study entry;
- With any mutations as follows :T315I、Y253F/H、E255K/V、F359C/V/I (if there are any other mutations,at physicians' discretion );
- Entry into another therapeutic clinical trial;
- Concomitant diseases that, according to the investigator's judgment, pose a serious risk to the patient's safety or completion of the study;
- History of neurological or psychiatric disorders, including epilepsy or dementia;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FlumatinibFlumatinib mesylate tablets 600mg qd for 24 months | Drug | flumatinib, nilotinib |
| NilotinibNilotinib Capsules 400mg bid for 24 months | Drug | flumatinib, nilotinib |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CML-CP; Mutation;Suboptimal Response or Failure in TKI, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weiming Li (13098815546, liweiming202012@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major molecular response rate at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.