Innate T Cells and TKI Discontinuation

Chronic Myeloid Leukemia Clinical Trial

— TIBIOP-LMC  

Official title:

Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04645706
• Other study ID #: TIBIOP-LMC
• Status: Active, not recruiting
• Start date: April 20, 2021
• Est. completion date: April 2028

Study information

• Verified date: August 2023
• Source: Poitiers University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 92
• Est. completion date: April 2028
• Est. primary completion date: April 2028
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Other:
• Characteristics of innate T cells
functional and phenotypic characteristics of innate T cells

Locations

Country	Name	City	State
France	C.H.U. de Poitiers	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
Poitiers University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)