Идёт набор NCT05605379

CML Pediatric ITK Response According to Molecular Identification at Diagnosis

— Наблюдательное Chronic Myeloid Leukemia

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: Next Generation Sequencing (DNA and RNA).
Кому может быть актуально: Состояния в реестре: Chronic Myeloid Leukemia. Базовые параметры: 6 лет — 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Франция
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

CML Pediatric ITK Response According to Molecular Identification at Diagnosis (CML Piramid

Обзор

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.

Подробное описание

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.

Вмешательства

Биопрепарат Next Generation Sequencing (DNA and RNA)
Targeted Next Generation Sequencing (DNA and RNA)

Первичные конечные точки

Complete cytogenetic response (CCR) [Срок оценки: At 12 months from TKI start]

Вторичные конечные точки (6)

Molecular response [Срок оценки: At 3, 12, 18 and 24 months]
Type of response according to ELN2020 criteria [Срок оценки: At 3, 12, 18 and 24 months]
Occurrence of secondary resistance [Срок оценки: At 3, 12, 18 and 24 months]
Occurrence of TK domain mutation [Срок оценки: At 3, 12 18 and 24 months]
Progression Free Survival (PFS) [Срок оценки: At 3, 12, 18 and 24 months]
Overall Survival (OS) [Срок оценки: At 3, 12, 18 and 24 months]

Критерии участия

Критерии включения

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)