TIBIOP-LMC: Innate T Cells and TKI Discontinuation

Sponsor
Poitiers University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04645706
Collaborator
(none)
100
84

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Characteristics of innate T cells

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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
100 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia
Anticipated Study Start Date :
Nov 1, 2020
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Nov 1, 2027

Outcome Measures

Primary Outcome Measures

  1. Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment [Day 0 (day of discontinuing treatment)]

    Proportion of the CD8+ Eomes+ KIR+ T cells among CD8+ T cells between patients in failure versus those in success after discontinuation of TKI treatment

  2. Compare phenotypic characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment [Day 0 (day of discontinuing treatment)]

    Phenotypic markers expression : CD49d, CD57, CD45RA et CCR7, CD25 et HLA-DR among total CD8+ T cells

  3. Compare the functionnality of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment [Day 0 (day of discontinuing treatment)]

    Functionality of LT CD8+ Eome+ KIR+ : expression of perforin and IFNgamma

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
All
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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Poitiers University Hospital

Investigators

  • Study Director: Emilie CAYSSIALS, Poitiers University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Poitiers University Hospital
ClinicalTrials.gov Identifier:
NCT04645706
Other Study ID Numbers:
  • TIBIOP-LMC
First Posted:
Nov 27, 2020
Last Update Posted:
Nov 27, 2020
Last Verified:
Nov 1, 2020
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 27, 2020