Leukemia, Myelogenous, Chronic PhaseNCT03131986
Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia
An observational study of Leukemia, Myelogenous, Chronic Phase, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelogenous, Chronic Phase
- How many people
- 30 participants
- Where
- 1 siteHong Kong
- Study dates
- 18 Apr 2017to 30 Mar 2019
- 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: All patients on TKI treatment for at least 3 years and DMR for at least 24 months and potentially eligible for the study will be recruited.
Who may be able to join
- Adult (aged 18 years or above) patients diagnosed with chronic-phase CML
- In deep molecular response (i.e. MR4.5 or below, or those whose breakpoint cluster region -Abelson murine leukemia (BCR-ABL) transcripts were undetectable with at least 20,000 amplified copies of the control gene) for at least 2 years, confirmed by at least 3 data points with no more than one assessment between MR4 and MR4.5
- Under treatment with a TKI in first line, or in second line due to intolerance of another first-line TKI
- At least three years of treatment with the same TKI before enrolment
Who cannot join
- Under 18 years old
- Adults under law protection or without ability to consent
- Previous or planned autologous/allogeneic haematopoietic stem cell transplantation
- Documented kinase domain mutation
- History of disease progression (accelerated or blast phase)
- A change to the current TKI because of unsatisfactory response to a previous TKI in those who are on second line TKI (Note: patients are still considered eligible if the switch of TKI was due to intolerance or side effects)
- Patients who can speak neither Chinese nor English
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
Yuk Man Cheung, MBBS(HK), 852-22554361 ext. 1654, drcarolcheung@gmail.com
Crosby Lu, MMedSc, 852-22551654, khlu@hku.hk
About this study
Official title: Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia Who Achieve Stable Deep Molecular Response
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.
Read the detailed description
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
- Conditions
- Leukemia, Myelogenous, Chronic Phase
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What is being measured
The primary outcome is the main question the study is designed to answer.
disease free survival
molecular relapse-free survival without treatment
Measured: 12 months
Secondary outcomes (2)
disease free survival
molecular relapse-free survival without treatment
Measured: 24 months
Overall survival
Overall survival without treatment
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2017
- Study start18 Apr 2017
- Primary completion30 Mar 2019 (estimated)
- Study completion30 Mar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myelogenous, Chronic PhaseStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Yok-lam Kwong, The University of Hong Kong
- Investigators
- Yuk Man Cheung, MBBS(HK), Principal investigator, Queen Mary Hospital, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03131986
- Sponsor's protocol ID
- QMH-CML-001
- Status last verified
- Jun 2018
- First submitted
- 24 Apr 2017
- Last updated
- 11 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010 Nov;11(11):1029-35. doi: 10.1016/S1470-2045(10)70233-3. Epub 2010 Oct 19.
PubMed 20965785Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, Gardembas M, Etienne G, Rea D, Roy L, Escoffre-Barbe M, Guerci-Bresler A, Tulliez M, Prost S, Spentchian M, Cayuela JM, Reiffers J, Chomel JC, Turhan A, Guilhot J, Guilhot F, Mahon FX. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014 Feb 10;32(5):424-30. doi: 10.1200/JCO.2012.48.5797. Epub 2013 Dec 9.
PubMed 24323036Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013 Jul 25;122(4):515-22. doi: 10.1182/blood-2013-02-483750. Epub 2013 May 23.
PubMed 23704092Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, Kim HJ, Kim SH, Zang DY, Oh S, Kim H, Do YR, Kwak JY, Kim JA, Kim DY, Mun YC, Lee WS, Chang MH, Park J, Kwon JH, Kim DW. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016 Jun;101(6):717-23. doi: 10.3324/haematol.2015.139899. Epub 2016 Feb 17.
PubMed 26888022
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous Leukaemia Who Achieve Stable Deep Molecular Response
- ClinicalTrials.gov ID
- NCT03131986
- Acronym / sponsor ID
- QMH-CML-001
- Conditions
- Leukemia, Myelogenous, Chronic Phase
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 30 Mar 2019 (estimated)
- Study completion
- 30 Mar 2019 (estimated)
- First posted
- 27 Apr 2017 (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.
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.
Detailed description
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 design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients on TKI treatment for at least 3 years and DMR for at least 24 months and potentially eligible for the study will be recruited.
Key inclusion criteria (4 listed)
- Adult (aged 18 years or above) patients diagnosed with chronic-phase CML
- In deep molecular response (i.e. MR4.5 or below, or those whose breakpoint cluster region -Abelson murine leukemia (BCR-ABL) transcripts were undetectable with at least 20,000 amplified copies of the control gene) for at least 2 years, confirmed by at least 3 data points with no more than one assessment between MR4 and MR4.5
- Under treatment with a TKI in first line, or in second line due to intolerance of another first-line TKI
- At least three years of treatment with the same TKI before enrolment
Key exclusion criteria (7 listed)
- Under 18 years old
- Adults under law protection or without ability to consent
- Previous or planned autologous/allogeneic haematopoietic stem cell transplantation
- Documented kinase domain mutation
- History of disease progression (accelerated or blast phase)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
disease free survival
Time frame: 12 months
molecular relapse-free survival without treatment
2 secondary outcomes
disease free survival
Time frame: 24 months
Overall survival
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2018.
- Results publication: PubMed 20965785Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010 Nov;11(11):1029-35. doi: 10.1016/S1470-2045(10)70233-3. Epub 2010 Oct 19.
- Results publication: PubMed 24323036Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, Gardembas M, Etienne G, Rea D, Roy L, Escoffre-Barbe M, Guerci-Bresler A, Tulliez M, Prost S, Spentchian M, Cayuela JM, Reiffers J, Chomel JC, Turhan A, Guilhot J, Guilhot F, Mahon FX. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014 Feb 10;32(5):424-30. doi: 10.1200/JCO.2012.48.5797. Epub 2013 Dec 9.
- Results publication: PubMed 23704092Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT, Dang P, Goyne JM, Slader C, Filshie RJ, Mills AK, Melo JV, White DL, Grigg AP, Hughes TP. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013 Jul 25;122(4):515-22. doi: 10.1182/blood-2013-02-483750. Epub 2013 May 23.
- Results publication: PubMed 26888022Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, Kim HJ, Kim SH, Zang DY, Oh S, Kim H, Do YR, Kwak JY, Kim JA, Kim DY, Mun YC, Lee WS, Chang MH, Park J, Kwon JH, Kim DW. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016 Jun;101(6):717-23. doi: 10.3324/haematol.2015.139899. Epub 2016 Feb 17.
- Individual participant dataSharing planned: Undecided
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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.
Yuk Man Cheung, MBBS(HK) principal investigator
Queen Mary Hospital, Hong Kong
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 Leukemia, Myelogenous, Chronic Phase, run by The University of Hong Kong at 1 site in Hong Kong.
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 4 inclusion and 7 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 11 Jun 2018. 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 Hong Kong. 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 Yuk Man Cheung, MBBS(HK) (85222555161, drcarolcheung@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease free survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03131986, which also lists 4 linked publications.
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 11 Jun 2018.