Clinical trial NCT04645706: Innate T Cells and TKI Discontinuation
Official title: Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Chronic Myeloid Leukemia
Lead sponsor: Poitiers University Hospital
Sponsor class: OTHER
First posted: 2020-11-27
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: CML patients for whom treatment with TKI is stopped according to the recommendations of the French Fi-LMC group.

Brief summary: After more than a decade of treating chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI), the discontinuation of treatment represents the expected new revolution. The investigators has recently discovered a new innate CD8+ T population in healthy subjects, the Eomes+ KIR+ CD8+ T population, with anti-tumor properties. Remarkably, these cells are numerically and functionally deficient in patients at diagnosis and then restored in patients in major molecular remission (MMR) on TKI. Our work performed in a retrospective pilot study interestingly shows a very significant increase in the proportion of CD8+ Eomes+ KIR+ T cells within total T cells in patients with prolonged success in stopping their ITK (≥ 2 years).Thus, the investigators postulate that CD8+ Eomes+ KIR+ T cells are a predictive signature of TKI arrest success in CML. The investigators will rely on a prospective translational study of this cell contingent during treatment cessation.

Detailed description: To perform this research, the investigators have started a prospective translational study to collect samples in CML patients with successful versus patients who have failed TKI therapy discontinuation. The investigators plan to study functional and phenotypic characteristics of innate T cells. The investigators also plan to evaluate in vitro whether immune check points inhibitors could help to restore the innate T lymphocytes population.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Diagnosis of CML-PC according to the criteria of the European Leukemia Net (Baccarani et al, 2013)
* Patients treated with TKI for at least 3 years (imatinib, nilotinib, dasatinib, bosutinib, ponatinib)
* Patients meeting the criteria of the French STIM study: deep molecular response of MR4.5 type (threshold of 0.0032%) or MR5 type (threshold of 0.001%) for at least 2 years,
* Free subject, without guardianship or curatorship or subordination
* Patients benefiting from a Social Security system or benefiting from it through a third party

Exclusion Criteria:

* Refusal to participate in the research
* Patients not benefiting from a Social Security scheme or not benefiting from it through a third party
* Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies
* Patient having stopped treatment for another reason than: deep molecular response of MR4.5 (threshold of 0.0032%) or MR5 (threshold of 0.001%) for at least 2 years

Translated with www.DeepL.com/Translator (free version)

Primary outcomes:
measure: Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
timeFrame: Day 0 (day of discontinuing treatment)
measure: Compare phenotypic characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
timeFrame: Day 0 (day of discontinuing treatment)
measure: Compare the functionnality of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
timeFrame: Day 0 (day of discontinuing treatment)
Secondary outcomes:
Other outcomes:
Locations:
city: Poitiers
country: France
facility: C.H.U. de Poitiers
Study officials:
affiliation: Poitiers University Hospital
name: Emilie CAYSSIALS
role: STUDY_DIRECTOR
References: