Value of Biological Age, in Addition to Individual Frailty, for Personalising the Management of Cancer Treated with Targeted Therapy (BIO-TIMER)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia,Myeloid, Chronic
• Intervention / Treatment: Biological: Blood and bone marrow sample

• Study Type: Interventional
• Enrollment (Estimated): 321
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: +33473754963; Email: promo_interne_drci@chu-clermontferrand.fr
• Study Contact Backup: Name: Mélanie CASILE, PhD; Phone Number: +33473750682; Email: mcasile@chu-clermontferrand.fr

Study Locations

• France
  • Annecy, France
    • Recruiting
    • CHU Annecy-Genevois
    • Contact: Anne PARRY, MD
  • Bordeaux, France
    • Not yet recruiting
    • Institut Bergonié
    • Contact: Gabriel ETIENNE, MD
  • Caen, France
    • Recruiting
    • CHU CAEN
    • Contact: Atchroue JOHNSON ANSAH, MD
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU de Clermont-Ferrand
    • Contact: Marc BERGER, Pr; Email: mberger@chu-clermontferrand.fr
    • Contact: Melanie CASILE, PhD; Phone Number: +33473750682; Email: mcasile@chu-clermont.fr
    • Contact: Eric Hermet, MD
    • Contact: Clément LAHAYE, MD
  • Créteil, France
    • Not yet recruiting
    • CHU CRETEIL
    • Contact: Lydia ROY, MD
  • Grenoble, France
    • Not yet recruiting
    • CHU Grenoble Alpes
    • Contact: Mathieu MEUNIER, MD
  • Le Puy-en-Velay, France
    • Recruiting
    • Centre Hospitalier Emile Roux
    • Contact: Vanessa PANTE, MD
    • Contact: Vanessa PANTE, Dr
  • Lille, France
    • Not yet recruiting
    • Chru Lille
    • Contact: valerie Coiteux, MD
  • Limoges, France
    • Recruiting
    • CHU Limoges
    • Contact: Amélie PENOT, MD
    • Contact: Jean Baptiste FARGEAS, MD
  • Lyon, France
    • Withdrawn
    • Centre Leon Berard
  • Marseille, France
    • Recruiting
    • Institut Paoli-Calmettes
    • Contact: Aude CHARBONNIER, MD
  • Nancy, France
    • Recruiting
    • CHU Nancy
    • Contact: Gabrielle ROTH-GUEPI, MD
    • Contact: Jean-Yves NIEMIER, MD
  • Paris, France
    • Recruiting
    • Groupe Hospitalier Paris Saclay - Site de Bicêtre
    • Contact: Laurence LEGROS, MD
    • Contact: Emanuelle DURON, MD
  • Rennes, France
    • Recruiting
    • Chu Rennes
    • Contact: Martine ESCOFFRE-BARBE, MD
  • Saint-Étienne, France
    • Recruiting
    • CHU Saint-Etienne
    • Contact: Philippe RENAUDIER, MD
    • Contact: Blandine DELAVIGERIE, MD
  • Toulouse, France
    • Recruiting
    • Institut Universitaire du Cancer de Toulouse - Oncopole
    • Contact: Françoise HUGUET, MD
    • Contact: Clément GAUDIN, MD
  • Versailles, France
    • Recruiting
    • CHU Versailles
    • Contact: Philippe ROUSSELOT, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All patients	Biological: Blood and bone marrow sample; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Marc BERGER, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): November 17, 2025
• Study Completion (Estimated): November 17, 2028

Study Registration Dates

• First Submitted: September 29, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Frailty; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: RBHP 2023 BERGER; 2023-A00974-41 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No