CML Pediatric ITK Response According to Molecular Identification at Diagnosis

NCT ID: NCT05605379

Last Updated: 2024-08-14

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 88 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-27
• Study Completion Date: 2025-03-31

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.

Detailed Description

Commonly mutated genes associated with myeloid malignancies have been described in acceleration phase and blastic phase but also at diagnostic in adult chronic phase-CML (CP-CML). The impact of these mutations on treatment response is still debated but several studies observed a worse outcome in adult patients with some mutations. In children only one study explored the molecular status of 30 genes in 21 children and young adults. They found a higher proportion of ASXL1 mutations in children than in adult They did not observed any significant difference in overall survival of ASXL1 mutated versus non-mutated patients but probably due the small size of the cohort. We propose here, to investigate retrospectively on DNA at diagnosis of 88 CP-CML children the mutation status of 64 genes by next generation sequencing and to see if there is an association with the response to TKI treatment. We will complete the molecular signature by analyzing the differentially genetic expression profile by RNA-seq on peripheral blood RNA of 8 patients with CCR at 12 months (and/or a BCR ::ABL1 IS ≤1%IS) and 8 patients with no CCR at 12 months.

Conditions

Chronic Myeloid Leukemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Responders (with CCR at 1 year)

Next Generation Sequencing (DNA and RNA)

Intervention Type: BIOLOGICAL

Targeted Next Generation Sequencing (DNA and RNA)

No responders (without CCR at 1 year)

Next Generation Sequencing (DNA and RNA)

Intervention Type: BIOLOGICAL

Targeted Next Generation Sequencing (DNA and RNA)

Interventions

Next Generation Sequencing (DNA and RNA)

Targeted Next Generation Sequencing (DNA and RNA)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Bordeaux, Service Hématologie Biologique

Bordeaux, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Stéphanie DULUCQ

Role: CONTACT

stephanie.dulucq@chu-bordeaux.fr

05 57 82 14 98

Facility Contacts

Stéphanie DULUCQ

Role: primary

stephanie.dulucq@chu-bordeaux.fr

Other Identifiers

CHUBX 2022/44

Identifier Type: -

Identifier Source: org_study_id