Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 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 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) - 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05753384
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Poitiers University Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Tyrosine Kinase Inhibitors, Chronic Myeloid Leukemia

Arms & Interventions

Arms

Experimental: continued treatment with TKI at 50% dose reduction

continued treatment with TKI at 50% dose reduction compared to dosing received at randomization and then stopped treatment 12 months after randomization

Active Comparator: continuation of TKI treatment without dose change

continued treatment with TKI at same dose compared to dosing received at randomization and then stopped treatment 12 months after randomization

Interventions

Drug: - treatment of TKI in CML

continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

Contact a Trial Team

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International Sites

Chu Angers, Angers, France

Status

Recruiting

Address

Chu Angers

Angers, ,

Site Contact

Corentin ORVAIN, Dr

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