Hematologic DiseasesECOSTIMNCT03540654
Budget Impact Analysis of Discontinuing Tyrosin Kinase Inhibitors in Patients With Chronic Myeloid Leukemia Achieving a Complete Molecular Response by Using Probabilistic Markov Approach
An observational study of Hematologic Diseases and Chronic Myeloid Leukemia, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
Chronic myeloid leukemia (CML) is a model of targeted therapy for human malignancies. Over the past decade, a broad array of drugs designed to selectively inhibit protein tyrosine kinases (PTK) [i.e., tyrosine kinase inhibitors, (TKI)] have emerged as novel therapies for cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Diseases, Chronic Myeloid Leukemia
- What is being tested?
- Budget impact
- How many people
- 355 participants
- Where
- 1 siteFrance
- Study dates
- 7 Dec 2016to Apr 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: A cohort of CML patients treated with TKI will be identified in the French nationwide claims and hospital database (SNIIRAM)
Who may be able to join
- Date of inclusion: date of the last TKI reimbursement before discontinuation which will be defined by the absence of any TKI reimbursement without the occurrence of death during at least 61 days following the 30-day coverage period of a TKI reimbursement;
- History: 3-year period;
- Follow-up: at least 1 year after inclusion or until death whatever occurs first.
- Patients aged 18 years or over;
- Patients with LTD registration or hospitalization for CML (primary, associated and linked ICD-10 diagnosis code, i.e. C92.1 or C921) during the study period;
- Patients who discontinued their TKI treatment for the first time during the inclusion period;
- Patients treated with TKI during the inclusion period with a minimum of 3 year-period of TKI regular treatment before TKI discontinuation. A 3 year-period of TKI regular treatment will be defined on the presence of at least 10 TKI reimbursements per year during the 3 years preceding TKI discontinuation.
Who cannot join
- Patients who proceeded to allogeneic or autogenic hematopoietic stem-cell transplant (hospitalization ICD-10 code diagnosis Z94.80) in the 3 year-period prior to or in the month following the last TKI reimbursement identified before TKI discontinuation;
- Patients with HIV/AIDS (hospitalization ICD-10 code diagnosis B24) or chronic Hepatitis C or B (hospitalization ICD-10 code diagnosis B18) in the 3 year-period prior to or in the month following the last TKI reimbursement identified before TKI discontinuation;
- Recent (i.e. in the previous year) or ongoing pregnancy at TKI discontinuation date identified by an algorithm based on codes of hospitalization diagnoses and medical procedures.
- Causes of TKI discontinuation will be further investigated in the cohort in order to conduct analyses only patients with a TKI discontinuation due to a complete molecular response.
Trial locations and contacts
1 site in 1 country.
About this study
Chronic myeloid leukemia (CML) is a model of targeted therapy for human malignancies. Over the past decade, a broad array of drugs designed to selectively inhibit protein tyrosine kinases (PTK) [i.e., tyrosine kinase inhibitors, (TKI)] have emerged as novel therapies for cancer patients. Hence, CML is an hematopoietic stem cell disorder in which a t(9;22) (q34;q11) reciprocal chromosomal translocation gives rise to Philadelphia chromosome (Ph) and generates the BCR-ABL1 fusion gene encoding a constitutively activated PTK. TKIs, such as imatinib by blocking BCR-ABL1 kinase activity, selectively eradicate CML cells and induce durable responses and prolong survival. CML patients treated with TKI are monitored by quantitative RT-PCR to detect leukemic BCR-ABL1 transcript performed from peripheral blood samples (1).
Since TKI treated CML patients have a near-normal life expectancy two important issues must be considered in the future:
Read more
- the quality of life and ethical aspects of a lifetime treatment,
- the budget impact for healthcare providers of treating patients during lifetime.
One of the best ways to consider these two points is to ask the question about stopping TKI in good responder patients. We first reported a pilot study where imatinib was withdrawn in 12 CML patients treated and maintained in complete molecular remission (CMR), defined by undetectable residual disease (with sensitivity of 4.5 log) on quantitative RT-PCR, for at least two years. Then, we demonstrated in a multicenter study entitled STIM trial that imatinib could be safely discontinued in patients with CMR for at least 2 years (2). All molecular relapsing patients were sensitive when imatinib was re-challenged (3). Around 40% of these patients remain in a prolonged treatment-free remission (TFR) after treatment cessation (4). Taking into account the cost of imatinib and the number of months without treatment in STIM trial, the savings in France were estimated to be 9 million €. However, since only 40 % of patients are in treatment free remission, a study, assessing the real budget impact of stopping TKI in the eligible population seems necessary as no published study has ever addressed this question in France.
Our aim is to assess the budget impact of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with treatment during lifetime, from the French healthcare system point of view. This budget impact will be expressed as a "net benefit" and will be based on the difference between total costs incurred by this strategy and total costs avoided also.
One of the originality of our study is to raise the issue of treatment cessation in the context of a chronic disease from an economic point of view.
The other originality of this study is to use a decision model to perform this French budget impact analysis of TKI discontinuation, without setting up another trial. Besides the literature review and meta-analysis; the proposed probabilistic Markov model will use direct costs (including treatment costs and all health care related costs as well as costs related to relapse) extracted mainly from the French Health Insurance Databases.
- Conditions
- Hematologic Diseases, Chronic Myeloid Leukemia
- Being tested
- Budget impact
- Medical subject headings
- Hematologic Diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Budget impactOther
Budget impact, using a probabilistic markov model, of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with current practice (treatment during entire life), from the healthcare system point of view
| Study group | Role | What they receive |
|---|---|---|
| Patients with CML discontinuing TKI treatment | Not described Receives: Other: Budget impact |
What is being measured
The primary outcome is the main question the study is designed to answer.
Budget impact of discontinuing TKI in patients with CML achieving a complete molecular response
Budget impact, of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with current practice (treatment during entire life), between 2008 and 2015 from the healthcare system point of view, by using a probabilistic Markov model
Measured: Patients treated since at least 3 years and achieving deep molecular response compared with current practice (treatment during entire life), between 2008 and 2015
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start7 Dec 2016
- Primary completionOct 2018
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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
- Retrospective
- Enrolment
- 355 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- Bordeaux PharmacoEpi
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03540654
- Sponsor's protocol ID
- CHUBX 2015/28
- Acronym
- ECOSTIM
- Status last verified
- Apr 2020
- First submitted
- 9 Apr 2018
- Last updated
- 28 Apr 2020
- Results posted
- No
- Data monitoring committee
- 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 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Budget Impact Analysis of Discontinuing Tyrosin Kinase Inhibitors in Patients With Chronic Myeloid Leukemia Achieving a Complete Molecular Response by Using Probabilistic Markov Approach
- ClinicalTrials.gov ID
- NCT03540654
- Acronym / sponsor ID
- ECOSTIM / CHUBX 2015/28
- Conditions
- Hematologic Diseases, Chronic Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 355 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- Bordeaux PharmacoEpi
- Study start
- 7 Dec 2016 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 30 May 2018 (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.
Chronic myeloid leukemia (CML) is a model of targeted therapy for human malignancies. Over the past decade, a broad array of drugs designed to selectively inhibit protein tyrosine kinases (PTK) [i.e., tyrosine kinase inhibitors, (TKI)] have emerged as novel therapies for cancer patients. Hence, CML is an hematopoietic stem cell disorder in which a t(9;22) (q34;q11) reciprocal chromosomal translocation gives rise to Philadelphia chromosome (Ph) and generates the BCR-ABL1 fusion gene encoding a constitutively activated PTK. TKIs, such as imatinib by blocking BCR-ABL1 kinase activity, selectively eradicate CML cells and induce durable responses and prolong survival. CML patients treated with TKI are monitored by quantitative RT-PCR to detect leukemic BCR-ABL1 transcript performed from peripheral blood samples (1).
Since TKI treated CML patients have a near-normal life expectancy two important issues must be considered in the future:
- the quality of life and ethical aspects of a lifetime treatment,
- the budget impact for healthcare providers of treating patients during lifetime.
One of the best ways to consider these two points is to ask the question about stopping TKI in good responder patients. We first reported a pilot study where imatinib was withdrawn in 12 CML patients treated and maintained in complete molecular remission (CMR), defined by undetectable residual disease (with sensitivity of 4.5 log) on quantitative RT-PCR, for at least two years. Then, we demonstrated in a multicenter study entitled STIM trial that imatinib could be safely discontinued in patients with CMR for at least 2 years (2). All molecular relapsing patients were sensitive when imatinib was re-challenged (3). Around 40% of these patients remain in a prolonged treatment-free remission (TFR) after treatment cessation (4). Taking into account the cost of imatinib and the number of months without treatment in STIM trial, the savings in France were estimated to be 9 million €. However, since only 40 % of patients are in treatment free remission, a study, assessing the real budget impact of stopping TKI in the eligible population seems necessary as no published study has ever addressed this question in France.
Our aim is to assess the budget impact of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with treatment during lifetime, from the French healthcare system point of view. This budget impact will be expressed as a "net benefit" and will be based on the difference between total costs incurred by this strategy and total costs avoided also.
One of the originality of our study is to raise the issue of treatment cessation in the context of a chronic disease from an economic point of view.
The other originality of this study is to use a decision model to perform this French budget impact analysis of TKI discontinuation, without setting up another trial. Besides the literature review and meta-analysis; the proposed probabilistic Markov model will use direct costs (including treatment costs and all health care related costs as well as costs related to relapse) extracted mainly from the French Health Insurance Databases.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with CML discontinuing TKI treatment | – | Other: Budget impact |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A cohort of CML patients treated with TKI will be identified in the French nationwide claims and hospital database (SNIIRAM)
Key inclusion criteria (7 listed)
- Date of inclusion: date of the last TKI reimbursement before discontinuation which will be defined by the absence of any TKI reimbursement without the occurrence of death during at least 61 days following the 30-day coverage period of a TKI reimbursement;
- History: 3-year period;
- Follow-up: at least 1 year after inclusion or until death whatever occurs first.
- Patients aged 18 years or over;
- Patients with LTD registration or hospitalization for CML (primary, associated and linked ICD-10 diagnosis code, i.e. C92.1 or C921) during the study period;
Key exclusion criteria (4 listed)
- Patients who proceeded to allogeneic or autogenic hematopoietic stem-cell transplant (hospitalization ICD-10 code diagnosis Z94.80) in the 3 year-period prior to or in the month following the last TKI reimbursement identified before TKI discontinuation;
- Patients with HIV/AIDS (hospitalization ICD-10 code diagnosis B24) or chronic Hepatitis C or B (hospitalization ICD-10 code diagnosis B18) in the 3 year-period prior to or in the month following the last TKI reimbursement identified before TKI discontinuation;
- Recent (i.e. in the previous year) or ongoing pregnancy at TKI discontinuation date identified by an algorithm based on codes of hospitalization diagnoses and medical procedures.
- Causes of TKI discontinuation will be further investigated in the cohort in order to conduct analyses only patients with a TKI discontinuation due to a complete molecular response.
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 |
|---|---|---|
| Budget impactBudget impact, using a probabilistic markov model, of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with current practice (treatment during entire life), from the healthcare system point of view | Other | Patients with CML discontinuing TKI treatment |
Primary outcome
Budget impact of discontinuing TKI in patients with CML achieving a complete molecular response
Time frame: Patients treated since at least 3 years and achieving deep molecular response compared with current practice (treatment during entire life), between 2008 and 2015
Budget impact, of discontinuing TKI treatment in patients with CML in deep molecular response since at least two years, compared with current practice (treatment during entire life), between 2008 and 2015 from the healthcare system point of view, by using a probabilistic Markov model
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2020.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hematologic Diseases and Chronic Myeloid Leukemia, run by University Hospital, Bordeaux at 1 site in France.
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 7 inclusion and 4 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: finished, as of the sponsor's last update on 28 Apr 2020. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Budget impact of discontinuing TKI in patients with CML achieving a complete molecular response (time frame: Patients treated since at least 3 years and achieving deep molecular response compared with current practice (treatment during entire life), between 2008 and 2015). 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 28 Apr 2020.