Innate T Cells and TKI Discontinuation

NCT04645706 | Active Not Recruiting

• 1 other identifier: TIBIOP-LMC
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI 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

  Day 0 (day of discontinuing treatment)

• Compare phenotypic characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment

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

  Day 0 (day of discontinuing treatment)

• Compare the functionnality of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment

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

  Day 0 (day of discontinuing treatment)

Interventions

Characteristics of innate T cells OTHER

functional and phenotypic characteristics of innate T cells

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Poitiers University Hospital: lead

Study Sites (1)

C.H.U. de Poitiers

Poitiers, 86000, France

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emilie CAYSSIALS

  Poitiers University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: November 27, 2020
• Study Start: April 20, 2021
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: August 4, 2023

Record last verified: 2023-08

Locations

FR (1)