Is There an Association Between Innate CD8+ T Cells and the Evolution of Tyrosine Kinase Inhibitor Resistance Mutations in Phi+ Hematological Malignancies.

NCT04965649 | Unknown

• 1 other identifier: NIMAO/2020-2/SC-01
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this project is to test whether low levels of BcrAbl1, despite the presence of resistance mutations, are related to high levels of innate CD8+ T cells, in the hypothesis that these cells have an anti-tumor role. This research aims to investigate:

• An association between the rate of innate CD8+ T cells and the evolution of Phi+ pathologies (Chronic Myeloid Leukemia and Philadelphia chromosome-positive Acute lymphocytic leukemia (Phi+ ALL) carrying a resistance mutation, according to the ELN 2013 and Phi LMC recommendations.
• An association between the level of innate CD8+ T cells and the expansion of TKI resistance clones, assessed as the number of BcrAbl1 copies carrying the mutation relative to the number of Abl1 copies.

Conditions

Leukemia; Myelogenous Leukemia; Chronic Leukemia; BCR-ABL Positive Acute Myeloid Leukemia

Keywords

Leukemia; Myelogenous Leukemia; Chronic Leukemia; BCR-ABL Positive; innate CD8+ T cells; Philadelphia chromosome-positive Acute lymphocytic leukemia

Outcome Measures

Primary Outcomes (6)

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Chronic Myeloid Leukemia: mutated BcrAbl1

  The number of copies of mutated BcrAbl1 / 1000 copies of Abl1 will be measured.

  1-6 months after collecting last sample

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Chronic Myeloid Leukemia: % of BcrAbl1

  The percentage of BcrAbl1 will be measured against total Abl1

  1-6 months after collecting last sample

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Chronic Myeloid Leukemia: % of innate CD8+ T cells

  The percentage of innate CD8+ T cells will be measured against total CD8+ T cells.

  1-6 months after collecting last sample

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Philadelphia+ Acute Lymphoblastic Leukemia:mutated BcrAbl1

  The number of copies of mutated BcrAbl1 / 1000 copies of Abl1 will be measured.

  1-6 months after collecting last sample

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Philadelphia+ Acute Lymphoblastic Leukemia:% of BcrAbl1

  The percentage of BcrAbl1 will be measured against total Abl1

  1-6 months after collecting last sample

• Association between innate CD8+ T cell population levels and the rate of progression of TKI resistance mutations in Philadelphia+ Acute Lymphoblastic Leukemia:% of innate CD8+ T cells

  The percentage of innate CD8+ T cells will be measured against total CD8+ T cells

  1-6 months after collecting last sample

Secondary Outcomes (2)

• Association between the rate of innate CD8+ T cells and the molecular response during Chronic myeloid Leukemia.

  1-6 months after collecting last sample

• Association between the rate of innate CD8+ T cells and the molecular response during Philadelphia + Acute Lymphoblastic Leukemia

  1-6 months after collecting last sample

Other Outcomes (46)

• Sex of patients in the Chronic Myeloid Leukemia group

  1-6 months after collecting last sample

• Age of patients in the Chronic Myeloid Leukemia group

  1-6 months after collecting last sample

• Blood count in the Chronic Myeloid Leukemia group: White blood cells

  1-6 months after collecting last sample

Study Arms (2)

Chronic Myeloid Leukemia

There will be approximately 10 patients with Chronic Myeloid Leukemia in this group

Genetic: Phenotyping of total and innate CD8+T cells by flow cytometry

Philadelphia+ Acute Lymphoblastic Leukemia

There will be approximately 20 patients with Philadelphia chromosome-positive Acute lymphocytic leukemia in this group

Genetic: Phenotyping of total and innate CD8+T cells by flow cytometry

Interventions

Phenotyping of total and innate CD8+T cells by flow cytometry GENETIC

Blood samples from patients in the active file of the Clinical Cytology and Cytogenetics Laboratory at Nîmes University Hospital will be analyzed (diagnosis already known). Samples will be representative of the different stages of the pathology. For patients with a confirmed diagnosis of Chronic Myeloid Leukemia and Philadelphia+ Acute Lymphoblastic Leukemia), the remaining whole blood sample taken as part of the usual management will be sent for phenotyping of CD8+ TL (total and innate) by flow cytometry. Phenotyping will be performed on samples pooled at the end of the recruitment period.

Also known as: Evaluation of clinical evolution of the pathology and response to treatment according to ELN 2013 criteria.

Chronic Myeloid Leukemia; Philadelphia+ Acute Lymphoblastic Leukemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from Philadelphia+malignant hemopathies (Chronic Myeloid Leukemia and Philadelphia+ Acute Lymphoblastic Leukemia ) followed by the Clinical and Cytogenetic Cytology Laboratory at Nîmes University Hospital.

You may qualify if:

• Chronic Myeloid Leukemia or Phi+ ALL patients with TKI resistance mutations being monitored by the Clinical Cytology and Cytogenetics Laboratory at Nîmes University Hospital.
• Pathology resulting from a BcrAbl1 fusion gene (CML or Phi+ ALL) and presence of a TKI resistance mutation.
• Patients affiliated to or beneficiaries of a health insurance scheme.
• Adult patients over18 years of age.

You may not qualify if:

• Blast crisis stage pathology (according to WHO 2017 criteria (Table2.01, p33, WHO classification of tumours of haematopoietic and lymphoid tissues, IARC 2017).
• Patients Under 18 years of age

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

CHU de Nîmes

Nîmes, Gard, 30029, France

RECRUITING

Related Publications (3)

• Soverini S, De Benedittis C, Castagnetti F, Gugliotta G, Mancini M, Bavaro L, Machova Polakova K, Linhartova J, Iurlo A, Russo D, Pane F, Saglio G, Rosti G, Cavo M, Baccarani M, Martinelli G. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants. BMC Cancer. 2016 Aug 2;16:572. doi: 10.1186/s12885-016-2635-0.

  PMID: 27485109 BACKGROUND

• Ernst T, Hoffmann J, Erben P, Hanfstein B, Leitner A, Hehlmann R, Hochhaus A, Muller MC. ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Haematologica. 2008 Sep;93(9):1389-93. doi: 10.3324/haematol.12964. Epub 2008 Jul 4.

  PMID: 18603549 BACKGROUND

• Cayuela JM, Chomel JC, Coiteux V, Dulucq S, Escoffre-Barbe M, Etancelin P, Etienne G, Hayette S, Millot F, Nibourel O, Nicolini FE, Rea D; pour la France Intergroupe des leucemies myeloides chroniques (Fi-LMC) et le Groupe des biologistes moleculaires des hemopathies malignes (GBMHM). [Recommendations from the French CML Study Group (Fi-LMC) for BCR-ABL1 kinase domain mutation analysis in chronic myeloid leukemia]. Bull Cancer. 2020 Jan;107(1):113-128. doi: 10.1016/j.bulcan.2019.05.011. Epub 2019 Jul 26. French.

  PMID: 31353136 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

For patients with a confirmed diagnosis of Phi+ hematological malignancy (Chronic Myeloid Leukemia and Phi+ ALL), the remaining whole blood sample taken during the usual management will be sent to the Immunology Laboratory at Nîmes University Hospital for phenotyping of CD8+ TL (total and innate) by flow cytometry. The phenotyping will be performed on the pooled samples at the end of the recruitment period

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Serge CARILLO, PharmD, PhD

CONTACT

+33 466 68 34 00; serge.carillo@chu-nimes.fr

Anissa MEGZARI

CONTACT

+33 466 68 42 36; drc@chu-nimes.fr

Study Design

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

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 16, 2021
• Study Start: January 1, 2021
• Primary Completion: July 1, 2024
• Study Completion: January 1, 2025
• Last Updated: August 30, 2023

Record last verified: 2023-08

Locations

FR (1)