Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated With Targeted Therapy

Study Overview
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Brief Summary
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French prospective multicenter, open-label study involving newly diagnosed CML patients. Two assessments will be performed during the follow-up of these patients: individual frailty using geriatric tools and individual biological aging determined by DNA methylation analysis.

Official Title
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Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated With Targeted Therapy: the Model of Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Conditions
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Leukemia,Myeloid, Chronic

Intervention / Treatment
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* Biological: Blood and bone marrow sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years CML in chronic phase at time of diagnosis. Diagnosis must be made no more than 3 months (90 days) prior to inclusion. Diagnosis of chronic-phase CML (European Leukemia Network [ELN] 2020 criteria; Baccarani et al 2013) with confirmation of a Philadelphia chromosome (Ph1). A cryptic Ph1 chromosome must be confirmed by FISH.Criteria must meet the definition of chronic phase CML BCR ::ABL1 transcript quantifiable by quantitative PCR 1st-line treatment with tyrosine kinase inhibitor No tyrosine kinase inhibitor or hydroxyurea treatment received prior to first blood sampling (at diagnosis) Signature of informed consent for CML Observatory and signature of informed consent for BIO-TIMER protocol Read and understand French Enrolled in a social security plan or beneficiary of such a plan Exclusion Criteria: CML in accelerated or blast phase Refusal to participate in the study Treatment started prior to inclusion Patients under guardianship, curatorship, deprivation of liberty or safeguard of justice Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br> | Biological: Blood and bone marrow sample<br>* Individual biological aging determined by DNA methylation analysis will be assessed at D0, M3 and M12. An optional bone marrow sample will be taken during the myelogram performed at diagnosis. Individual fragility and quality of life will be assessed using geriatric tools at D0, M6, M12, M24 and M36<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological age determination | The difference between biological age and chronological age (of the clone and the patient) expressed as a difference and as a percentage. | Day 0;Month 3;Month 12 | 
| Individual fragility assessment | Individual fragility assessed by Geriatric Core Data set assessing social status, independence at home, mobility, nutrition, cognitive status, mood and comorbidities. | Day 0;Month 6;Month 12;Month 24;Month 36 | 
| Individual fragility assessment | Individual fragility assessed by Rockwood clinical frailty score ranging from 1 (very fit) to 9 (at the end of life) | Day 0;Month 6;Month 12;Month 24;Month 36 | 
| Tolerance of tyrosine kinase inhibitors | Tolerance assessed by actual dose received | Day 0;Month 3;Month 6;Month 12;Month 24;Month 36 | 
| Tolerance of tyrosine kinase inhibitors | Tolerance assessed by the number of tyrosine kinase inhibitor discontinuation due to intolerance | Day 0;Month 3;Month 6;Month 12;Month 24;Month 36 | 
| Tolerance of tyrosine kinase inhibitors | Tolerance assessed by a description of adverse events as assessed by CTCAE v5.0 | Day 0;Month 3;Month 6;Month 12;Month 24;Month 36 | 
| Tolerance of tyrosine kinase inhibitors | Tolerance assessed by changes and number of tyrosine kinase inhibitor lines | Day 0;Month 3;Month 6;Month 12;Month 24;Month 36 | 
| Tolerance of tyrosine kinase inhibitors | Tolerance assessed by a description of treatment sequences | Day 0;Month 3;Month 6;Month 12;Month 24;Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of individual clinical fragility levels assessed by Geriatric Core Data set at the time of diagnosis. | Individual fragility assessed by Geriatric Core Data set assessing social status, independence at home, mobility, nutrition, cognitive status, mood and comorbidities at the time of diagnosis. | Day 0 | 
| Distribution of individual clinical fragility levels assessed by Rockwood clinical frailty score at the time of diagnosis. | Individual fragility assessed by Rockwood clinical frailty score ranging from 1 (very fit) to 9 (at the end of life) at the time of diagnosis. | Day 0 | 
| Evaluation of therapeutic response through quantification of the BCR::ABL transcript | Quantification of BCR::ABL transcript expressed as copy number relative to 100 copies of control gene transcripts | Month 3;Month 6;Month 12;Month 15;Month 18;Month 21;Month 24;Month 27;Month 30;Month 33;Month 36 | 
| Assessment of therapeutic response by quantification of residual disease | Decrease in residual disease and achievement of MMR (≤0.1%), MR4 (≤0.01%), MR4.5 (≤0.032%), MR5 (≤0.001%) thresholds) | Month 3;Month 6;Month 12;Month 15;Month 18;Month 21;Month 24;Month 27;Month 30;Month 33;Month 36 | 
| Assessment of patients' quality of life | Quality of life assessed using the European Organisation for Research and Treatment of Cancer LG Core Questionnaire (EORTC QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients, with a higher score indicating a better health-related quality of life | Day 0;Month 6;Month 12;Month 24;Month 36 |