Innate T-cells as a Biomarker of Successful TKI Arrest in Chronic Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Compare the quantitative characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
时间窗: 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
Compare the functionnality of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
时间窗: Day 0 (day of discontinuing treatment)
Functionality of LT CD8+ Eome+ KIR+ : expression of perforin and IFNgamma
Compare phenotypic characteristics of the CD8+ Eomes+ KIR+ T cells between patients in failure versus those in success after discontinuation of TKI treatment
时间窗: Day 0 (day of discontinuing treatment)
Phenotypic markers expression : CD49d, CD57, CD45RA et CCR7, CD25 et HLA-DR among total CD8+ T cells
次要结局
未报告次要终点