CML Pediatric ITK Response According to Molecular Identification at Diagnosis

NCT05605379 | Recruiting

• 1 other identifier: CHUBX 2022/44
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of chronic myeloid leukemia (CML) has been revolutionized by tyrosine kinase inhibitor (TKI). Nevertheless, case of failure and suboptimal response are still observed even in children. Pediatric CML is a rare disease and differs from adult in terms of disease presentation and treatment response underlying a likely different CML biology. Molecular mechanisms that induce resistance to TKI are still poorly characterized except mutations in the tyrosine kinase domain of BCR::ABL1. We propose to search for a molecular signature to predict the response to TKI in the pediatric population.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia; Children; Molecular landscape; TKI response; Expression profile

Outcome Measures

Primary Outcomes (1)

• Complete cytogenetic response (CCR)

  We will analyse the impact of the presence of mutations on the obtention of CCR

  At 12 months from TKI start

Secondary Outcomes (6)

• Molecular response

  At 3, 12, 18 and 24 months

• Type of response according to ELN2020 criteria

  At 3, 12, 18 and 24 months

• Occurrence of secondary resistance

  At 3, 12, 18 and 24 months

• Occurrence of TK domain mutation

  At 3, 12 18 and 24 months

• Progression Free Survival (PFS)

  At 3, 12, 18 and 24 months

Study Arms (2)

Responders (with CCR at 1 year)

Biological: Next Generation Sequencing (DNA and RNA)

No responders (without CCR at 1 year)

Biological: Next Generation Sequencing (DNA and RNA)

Interventions

Next Generation Sequencing (DNA and RNA) BIOLOGICAL

Targeted Next Generation Sequencing (DNA and RNA)

No responders (without CCR at 1 year); Responders (with CCR at 1 year)

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric CML patients

You may qualify if:

• Age at diagnosis less than or equal to 18 years
• Presence of a Philadelphia chromosome detected by cytogenetic analysis (conventional karyotype or Fluorescence In Situ Hybridization (FISH)) and a BCR ::ABL1 transcript e13a2 ou e14a2
• Diagnosis in chronic phase according to the European Leukemia Net (ELN) criteria
• First-line treatment with TKIs
• Possible pre-treatment with hydroxyurea
• DNA available at diagnosis
• RNA available for a sub-group patients (8 responders vs 8 no responders)

You may not qualify if:

• Age at diagnosis more than 18 years
• Diagnosis in accelerated phase or blastic phase
• First line treatment other than TKI

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux, Service Hématologie Biologique

Bordeaux, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

High-Throughput Nucleotide Sequencing; DNA; RNA

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

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Stéphanie DULUCQ

CONTACT

05 57 82 14 98; stephanie.dulucq@chu-bordeaux.fr

Study Design

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

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: November 4, 2022
• Study Start: February 27, 2023
• Primary Completion: January 1, 2025
• Study Completion: March 1, 2025
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

FR (1)