Chronic Myeloid LeukemiaCML PiramidNCT05605379
CML Pediatric ITK Response According to Molecular Identification at Diagnosis
An observational study of Chronic Myeloid Leukemia, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Next Generation Sequencing (DNA and RNA)
- How many people
- 88 participants
- Where
- 1 siteFrance
- Study dates
- 27 Feb 2023to Mar 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric CML patients
Who may be able to join
- 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)
Who cannot join
- Age at diagnosis more than 18 years
- Diagnosis in accelerated phase or blastic phase
- First line treatment other than TKI
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU de Bordeaux, Service Hématologie Biologique
Bordeaux
Stéphanie DULUCQ, stephanie.dulucq@chu-bordeaux.fr
About this study
Official title: CML Pediatric ITK Response According to Molecular Identification at Diagnosis (CML Piramid
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.
Read the 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
- Being tested
- Next Generation Sequencing (DNA and RNA)
- Keywords
- Chronic Myeloid Leukemia, Children, Molecular landscape, TKI response, Expression profile
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Next Generation Sequencing (DNA and RNA)Biological
Targeted Next Generation Sequencing (DNA and RNA)
| Study group | Role | What they receive |
|---|---|---|
| Responders (with CCR at 1 year) | Not described Receives: Biological: Next Generation Sequencing (DNA and RNA) | |
| No responders (without CCR at 1 year) | Not described Receives: Biological: Next Generation Sequencing (DNA and RNA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete cytogenetic response (CCR)
We will analyse the impact of the presence of mutations on the obtention of CCR
Measured: At 12 months from TKI start
Secondary outcomes (6)
Molecular response
We will analyse the impact of the presence of mutations on the obtention of molecular response (MR4, MMR)
Measured: At 3, 12, 18 and 24 months
Type of response according to ELN2020 criteria
We will analyse the impact of the presence of mutations on the type of response
Measured: At 3, 12, 18 and 24 months
Occurrence of secondary resistance
We will analyse the impact of the presence of mutations on the occurrence of loss of complete hematologic, and/or cytogenetic and/or molecular responses
Measured: At 3, 12, 18 and 24 months
Occurrence of TK domain mutation
We will analyse the impact of the presence of mutations on the occurrence of mutation in the TK domain ABL1
Measured: At 3, 12 18 and 24 months
Progression Free Survival (PFS)
Progression to accelerated phase or blast crisis and deaths will be analysis according to the mutational status
Measured: At 3, 12, 18 and 24 months
Overall Survival (OS)
We will analyse the impact of the presence of mutations on OS
Measured: At 3, 12, 18 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2022
- Study start27 Feb 2023
- Primary completionJan 2025 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05605379
- Sponsor's protocol ID
- CHUBX 2022/44
- Acronym
- CML Piramid
- Status last verified
- Aug 2024
- First submitted
- 12 Oct 2022
- Last updated
- 14 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CML Pediatric ITK Response According to Molecular Identification at Diagnosis (CML Piramid
- ClinicalTrials.gov ID
- NCT05605379
- Acronym / sponsor ID
- CML Piramid / CHUBX 2022/44
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Chronic Myeloid Leukemia, Children, Molecular landscape, TKI response, Expression profile
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 27 Feb 2023 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 4 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Pediatric CML patients
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- Age at diagnosis more than 18 years
- Diagnosis in accelerated phase or blastic phase
- First line treatment other than TKI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Next Generation Sequencing (DNA and RNA)Targeted Next Generation Sequencing (DNA and RNA) | Biological | No responders (without CCR at 1 year), Responders (with CCR at 1 year) |
Primary outcome
Complete cytogenetic response (CCR)
Time frame: At 12 months from TKI start
We will analyse the impact of the presence of mutations on the obtention of CCR
6 secondary outcomes
Molecular response
Time frame: At 3, 12, 18 and 24 months
Type of response according to ELN2020 criteria
Time frame: At 3, 12, 18 and 24 months
Occurrence of secondary resistance
Time frame: At 3, 12, 18 and 24 months
Occurrence of TK domain mutation
Time frame: At 3, 12 18 and 24 months
Progression Free Survival (PFS)
Time frame: At 3, 12, 18 and 24 months
Overall Survival (OS)
Time frame: At 3, 12, 18 and 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Myeloid Leukemia, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stéphanie DULUCQ (05 57 82 14 98, stephanie.dulucq@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete cytogenetic response (CCR) (time frame: At 12 months from TKI start). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024; AzTrials last refreshed its copy on 6 Nov 2026.