Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia
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|ClinicalTrials.gov Identifier: NCT03131986|
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : June 11, 2018
Since the debut of imatinib, the first tyrosine kinase inhibitor(TKI), more than two decades ago, the prognosis of patients with chronic myelogenous leukaemia (CML) has continued to improve. It has been shown that life expectancy of CML patients is approaching that of the general population nowadays. Currently, indefinite use of TKIs in patients with chronic-phase CML who achieve optimal response remains the standard practice. Nevertheless, the concepts of "treatment-free remission" and "functional" cure have been hotly discussed in recent years. A number of major international clinical trials have demonstrated that about 40-60% of CML patients who previously enjoyed deep molecular response on TKI manage to stay free from molecular relapse after cessation of TKI therapy.
Local experience of TKI cessation is lacking. This study aims to recruit patients diagnosed with CML, chronic phase who are treated with TKIs and remain in stable deep molecular response for at least two years. It is planned to stop TKI in these patients with regular monitoring, and determine their outcomes.
|Condition or disease|
|Leukemia, Myelogenous, Chronic Phase|
Major clinical trials including multicentre Stop Imatinib (STIM) trial, According to Stop Imatinib (A-STIM), TWISTER, Korean Imatinib Discontinuation Study (KIDS), European Stop Tyrosine Kinase Inhibitor Trial (EURO-SKI), and stop second generation (2G-TKI) showed that it is safe to stop TKI in patients who achieve stable deep molecular response (DMR) as defined by respective study groups. Around 40-60% of study participants managed to remain in treatment-free remission (TFR). For patients who experience molecular relapse after TKI withdrawal, most do so within the first 6 months. In addition, they all remained sensitive to TKI and majority of them were able to achieve the original molecular response. No loss of complete haematological response or progression to advanced phase CML was observed when the TKI was stopped.
Cessation of TKI in selected CML patients leads to freedom from treatment-related toxic effects. It is expected that at least 40% of enrolled patients will be in a sustained molecular remission after stopping TKI. Successful cessation would also reduce long-term treatment costs.
After cessation of TKI, fluctuation in molecular response, or even molecular relapse of the disease might bring about anxiety and distress in the patients. Some patients, estimated at around 40-60%, would experience molecular relapse and require resumption of TKI. Close molecular monitoring real-time polymerase chain reaction (RT-QPCR) after stopping TKI (every month in the first year and every 2 months in the second year) will allow early detection of possible molecular relapse and thus prompt resumption of TKI. Long-term risks of disease progression and drug resistance are uncertain, though the safety data from the TFR studies reported to date are sufficiently reassuring. Some patients might have musculoskeletal pain and pruritus after cessation of TKI, especially imatinib, which is also commonly known as "imatinib withdrawal syndrome".
Patients with chronic-phase CML who have been treated with a tyrosine kinase inhibitor for more than 3 years and had deep molecular response (breakpoint cluster region/Abelson murine leukemia (BCR-ABL1) transcript ≤0.0032% IS ratio, i.e. molecular response (MR4.5) for at least 2 years
|Study Type :||Observational|
|Estimated Enrollment :||30 participants|
|Official Title:||Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia Who Achieve Stable Deep Molecular Response|
|Actual Study Start Date :||April 18, 2017|
|Estimated Primary Completion Date :||March 30, 2019|
|Estimated Study Completion Date :||March 30, 2019|
- disease free survival [ Time Frame: 12 months ]molecular relapse-free survival without treatment
- disease free survival [ Time Frame: 24 months ]molecular relapse-free survival without treatment
- Overall survival [ Time Frame: 24 months ]Overall survival without treatment
Biospecimen Retention: Samples With DNA
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): NCT03131986
|Contact: Yuk Man Cheung, MBBS(HK)||email@example.com|
|Contact: Crosby Lu, MMedScfirstname.lastname@example.org|
|Principal Investigator:||Yuk Man Cheung, MBBS(HK)||Queen Mary Hospital, Hong Kong|