Tyrosine Kinase InhibitorsPhase 3NCT05753384
Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System
A Phase 3 study testing treatment of TKI in CML in people with Tyrosine Kinase Inhibitors and Chronic Myeloid Leukemia, run by Poitiers University Hospital at 20 sites in France.
Trial summary
Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tyrosine Kinase Inhibitors, Chronic Myeloid Leukemia
- What is being tested?
- treatment of TKI in CML
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 20 sitesFrance
- Study dates
- 1 Dec 2023to 1 Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patient ≥ 18 year-old.
- Diagnosis of chronic phase CML according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2 or e14a2)
- Duration of treatment by Imatinib ≥ 4 years / ITK2G ≥ 3 years /Imatinib and ITK2G ≥ 4 years and no change of TKI or decrease in dosage in the last 6 months prior to inclusion
- Deep Molecular Response (DMR) duration ≥ 1 year
- Absence of contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations nd the PCR of each TKI:
- Imatinib (≥ 300 mg/j) Dasatinib (≥ 50 mg/j) Nilotinib (≥ 300 mg/j) Bosutinib (≥ 200 mg/j)
Show all 18Show fewer
- Patient not participating in another interventional study for the duration of the interventional study
- Sexually active men should use effective contraception when taking Dasatinib
- Having an health insurance
- Having signed the consent form
- Non-Inclusion Criteria:
- Patients with progressive severe pathology of poor prognosis immediately compromising participation in the entire study and/or with uncontrolled chronic pathology
- ECOG ≥ 3
- Prior resistance to TKI
- Patients who have already experienced an attempt of TKI cessation
- Patients with a malignant tumour that has been treated with chemotherapy within 2 months of inclusion or undergoing chemotherapy or that will be treated with post-inclusion chemotherapy
- Protected person
- Pregnant women or women of childbearing age without appropriate contraceptive measures
Who cannot join
None listed.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
France20 sites
Chu Angers
Angers
Ch Annecy
Annecy
Ch Bayonne
Bayonne
Chu Brest
Brest
CH Brive la Gaillarde
Brive-la-Gaillarde
Ch Chambery
Chambéry
CHI Creteil
Créteil
Ch La Rochelle
La Rochelle
Chu Lille
Lille
CHU Limoges
Limoges
Centre Léon Bérard
Lyon
Ch Mont de Marsan
Mont-de-Marsan
Chu Nancy
Nancy
Chu Nantes
Nantes
Hopital Prive Du Confluent
Nantes
Ch Perigueux
Périgueux
Chu Poitiers
Poitiers
Oncopole Toulouse
Toulouse
Chu Tours
Tours
CH Versailles
Versailles
About this study
Official title: Discontinuation of TyrosIne Kinase Inhibitors (ITK) in Chronic Myeloid Leukemia (LMC) and Impact on the Immune System: a Randomized Comparative Study of Two Therapeutic Strategies
Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. The ability to permanently stop treatment with TKI has thus become a major goal in CML to prevent the occurrence of adverse events, improve quality of life and reduce the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now remains to be demonstrated in a comparative prospective study that a strategy of de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR results. At the same time, it is possible to reduce adverse reactions and improve the quality of life of patients. In this context, the investigator propose to conduct a randomized clinical trial including CML patients, allowing to compare the results of TFR at 24 months between a sudden stop of treatment after a maintenance phase of dosage for 12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before stopping. A secondary immunological translational objective of this project will be to compare the quantitative and qualitative evolution of innate CD8 T cells between the 2 arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a predictive innate CD8 T cells blood signature at the time of stopping treatment of a successful TFR in both arms.
- Being tested
- treatment of TKI in CML
- Keywords
- Characteristics of innate T cells
- Medical subject headings
- 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.
treatment of TKI in CMLDrug
continued treatment with TKI at randomization a then stopped treatment 12 months after randomization
| Study group | Role | What they receive |
|---|---|---|
| continued treatment with TKI at 50% dose reduction | Experimental | continued treatment with TKI at 50% dose reduction compared to dosing received at randomization and then stopped treatment 12 months after randomization Receives: Drug: treatment of TKI in CML |
| continuation of TKI treatment without dose change | Active comparator | continued treatment with TKI at same dose compared to dosing received at randomization and then stopped treatment 12 months after randomization Receives: Drug: treatment of TKI in CML |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients.Treatment-Free Remission (TFR) is defined as patients with Major Molecular Response (MMR) or better (BCR-ABL level ≤ 0.1% IS).
Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL level ≤ 0.1% IS) on the total number of patients.
Measured: 24 months after treatment discontinuation
Secondary outcomes (1)
Difference in proportions (%) at randomization and 12 months post randomization, of innate CD8 T cells among total CD8 T cells
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 posted3 Mar 2023
- Study start1 Dec 2023
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tyrosine Kinase InhibitorsStudies of the same condition, open and under way.
- More trials run by Poitiers University HospitalThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Poitiers University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05753384
- Sponsor's protocol ID
- AITIK
- Status last verified
- Apr 2026
- First submitted
- 9 Feb 2023
- Last updated
- 27 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discontinuation of TyrosIne Kinase Inhibitors (ITK) in Chronic Myeloid Leukemia (LMC) and Impact on the Immune System: a Randomized Comparative Study of Two Therapeutic Strategies
- ClinicalTrials.gov ID
- NCT05753384
- Acronym / sponsor ID
- AITIK
- Keywords
- Characteristics of innate T cells
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Poitiers University HospitalUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2029 (estimated)
- First posted
- 3 Mar 2023 (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.
Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. The ability to permanently stop treatment with TKI has thus become a major goal in CML to prevent the occurrence of adverse events, improve quality of life and reduce the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now remains to be demonstrated in a comparative prospective study that a strategy of de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR results. At the same time, it is possible to reduce adverse reactions and improve the quality of life of patients. In this context, the investigator propose to conduct a randomized clinical trial including CML patients, allowing to compare the results of TFR at 24 months between a sudden stop of treatment after a maintenance phase of dosage for 12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before stopping. A secondary immunological translational objective of this project will be to compare the quantitative and qualitative evolution of innate CD8 T cells between the 2 arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a predictive innate CD8 T cells blood signature at the time of stopping treatment of a successful TFR in both arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| continued treatment with TKI at 50% dose reduction | Experimental | Drug: treatment of TKI in CMLcontinued treatment with TKI at 50% dose reduction compared to dosing received at randomization and then stopped treatment 12 months after randomization |
| continuation of TKI treatment without dose change | Active comparator | Drug: treatment of TKI in CMLcontinued treatment with TKI at same dose compared to dosing received at randomization and then stopped treatment 12 months after randomization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient ≥ 18 year-old.
- Diagnosis of chronic phase CML according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2 or e14a2)
- Duration of treatment by Imatinib ≥ 4 years / ITK2G ≥ 3 years /Imatinib and ITK2G ≥ 4 years and no change of TKI or decrease in dosage in the last 6 months prior to inclusion
- Deep Molecular Response (DMR) duration ≥ 1 year
- Absence of contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations nd the PCR of each TKI:
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| treatment of TKI in CMLcontinued treatment with TKI at randomization a then stopped treatment 12 months after randomization | Drug | continuation of TKI treatment without dose change, continued treatment with TKI at 50% dose reduction |
Primary outcome
Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients.Treatment-Free Remission (TFR) is defined as patients with Major Molecular Response (MMR) or better (BCR-ABL level ≤ 0.1% IS).
Time frame: 24 months after treatment discontinuation
Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL level ≤ 0.1% IS) on the total number of patients.
1 secondary outcome
Difference in proportions (%) at randomization and 12 months post randomization, of innate CD8 T cells among total CD8 T cells
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
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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.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing treatment of TKI in CML in people with Tyrosine Kinase Inhibitors and Chronic Myeloid Leukemia, run by Poitiers University Hospital at 20 sites 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 18 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients.Treatment-Free Remission (TFR) is defined as patients with Major Molecular Response (MMR) or better (BCR-ABL level ≤ 0.1% IS). (time frame: 24 months after treatment discontinuation). 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 27 Apr 2026.