Interest of PHARMaceutical Conciliation to Understand Drug Interactions, Phytotherapy, and Targeted Therapies in Chronic Myeloid Leukemia (PHARM-LMC)

Interest of PHARMaceutical Conciliation to Understand Drug Interactions, Phytotherapy, and Targeted Therapies in Chronic Myeloid Leukemia: PHARM-LMC Study

The aim of this trial is therefore to identify concomitant treatments with taking Tyrosine Kinase Inhibitor (=TKI) in the indication of Chronic Myeloid Leukemia (CML), whatever the stage of the disease, via pharmaceutical conciliation. These concomitant treatments as well as their dosages will be correlated with the TKI dosage since patients must have a sufficient residual concentration to be considered effective and to confirm adherence to treatment, the leading cause of treatment failure.

In the event of unsatisfactory results, pharmaceutical interventions may take place: changes in treatments (TKI and not TKI) and / or dosages. In case of modification, a new dosage of TKI should be carried out.

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia
• Intervention / Treatment: Other: Pharmaceutical intervention

Detailed Description

Chronic myeloid leukemia (CML) is a clonal myeloproliferative syndrome with an estimated incidence of 0.8-1 cases per 100,000 person-years in 2018 in France. CML is characterized by the transformation of a pluripotent stem cell resulting in an increase in myeloid and erythroid lineages and megakaryocytes in peripheral blood as well as myeloid hyperplasia in the bone marrow.

In the absence of treatment, the disease, which begins in a chronic phase over a few years, progresses to an acceleration phase, before reaching an acute phase, known as a blast crisis, with a poor prognosis. This abnormal proliferation of white blood cells results from the reciprocal translocation (exchange) between chromosomes 9 and 22. This exchange brings two normally distinct genes into contact: the (breakpoint cluster region) BCR gene and the abl gene (Tyrosine-protein kinase), which will form an abnormal gene called "fusion Bcr-abl". This gene encodes a fusion protein with deregulated tyrosine kinase activity that activates various mechanisms involved in cell multiplication.

Since the 1990s, the arrival of the first tyrosine kinase inhibitor (TKI), imatinib, has radically changed patient management. Indeed, according to Public Health France, this treatment has allowed the majority of patients to remain in the chronic phase for a long time. Patient survival has therefore increased dramatically as the life expectancy of patients with CML taking their treatment regularly approaches that of the general population.

However, even though several generations of TKI have been developed, certain toxicities may lead to discontinuation of treatment, or to a modification of the dose. Indeed, a meta-analysis published in June 2020 shows that second and third generation of TKI improve the major molecular response by 3 months, but are associated with a recrudescence of thrombocytopenia, cardiovascular, pancreatic and hepatic events. First generation imatinib therefore remains the best option for patients with co-morbidities despite the frequent presence of headaches, digestive disorders, and cramps.

It has therefore always been customary to change the TKI or modify the prescribed doses, while the side effects or ineffectiveness of these inhibitors could be explained by drug interactions, or be related to the use of herbal medicine. Indeed, TKIs are metabolized by the cytochrome P450 system. The activity of this cytochrome is not only different from one person to another, but can also be affected by other treatments. For example, some treatments will inhibit the activity of this cytochrome P450, increasing the exposure of TKIs in plasma. The pharmacokinetics of the drug will therefore depend on these concomitant treatments and their influence, among others, on cytochrome P450.

In addition, the median age at diagnosis is respectively 61 years for men and 62 years for women. These patients are therefore often carriers of other chronic diseases and are have multiple treatments.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandrine Menguy, MD, PhD; Phone Number: +33 0477917136; Email: sandrine.menguy@chu-st-etienne.fr
• Study Contact Backup: Name: Mathilde Maison, MsC; Phone Number: +33 0477917136; Email: mathilde.maison@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France, 42055
    • Recruiting
    • CHU DE SAINT-ETIENNE
    • Contact: Sandrine Menguy, MD, PhD; Phone Number: +33 0477917136; Email: sandrine.menguy@chu-st-etienne.fr
    • Contact: Mathilde Maison, MsC; Phone Number: +33 0477917136; Email: mathilde.maison@chu-st-etienne.fr
    • Sub-Investigator: Karine AUGEUL MEUNIER
    • Sub-Investigator: Silvia Maria BEZSERA
    • Sub-Investigator: Emilie CHALAYER
    • Sub-Investigator: Philippe COLLET
    • Sub-Investigator: Jérôme CORNILLON
    • Sub-Investigator: Caroline LEJEUNE
    • Sub-Investigator: Thierry MURON
    • Sub-Investigator: Gilbert SOGLU
    • Sub-Investigator: Emmanuelle TAVERNIER TARDY
    • Sub-Investigator: Pauline DOUCEY
    • Sub-Investigator: Fabien FORGES
    • Sub-Investigator: Sophie KALFON
    • Sub-Investigator: Agnès MACE
    • Sub-Investigator: Denis Guyotat
    • Sub-Investigator: Ludovic Fouillet
    • Sub-Investigator: Fressia Honeyman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Major patient;
• Patient affiliated to a social security scheme;
• Patient suffering from Chronic Myeloid Leukemia, taking a Tyrosine Kinase Inhibitor (Imatinib, Nilotinib, Dasatinib, or Bosutinib);
• Molecular response < 4,5 Log;

Exclusion Criteria:

• Legal incapacity or limited capacity ; Medical or psychological incapacity or limited capacity;
• Not able to read and/or to write French;
• Patient taking Ponatinib.

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: Pharmaceutical conciliation; Patients with Chronic Myeloid Leukemia taking TKI with a molecular response < 4,5 Log will participate to pharmaceutical conciliation.	Other: Pharmaceutical intervention; Patients with pharmacokinetic and/or pharmacodynamics interactions will be proposed to participate to educational sessions to discuss about treatments taken and modifications possibilities.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients for whom pharmaceutical interventions have been done	Number of patients for whom pharmaceutical interventions have been done secondly to pharmaceutical conciliation will be reported.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular response	Molecular response will be reported via BCR-ABL transcript rate measured by quantitative polymerase chain reaction (qPCR) or digital polymerase chain reaction (PCR).	12 months
Concomitant treatments	Concomitant treatments will be reported during 12 months.	12 months
Tyrosine kinase inhibitor observance	Observance to Tyrosine kinase inhibitor will be measured with Girerd Questionnaire.	12 months
Side effects	Number and description of sides effects will be reported.	12 months
Patients' satisfaction	Patients' satisfaction will be measured with a visual scale from 0 to 10.	12 months
Patients' quality of life	Patients' quality of life will be measured with the Quality of Life questionnaires (QLQ-C30) questionnaire. The maximum score is 126, the minimum score is 30. More the score is, worst the health state is.	12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Institut de Cancérologie de la Loire
• Investigators: Principal Investigator: Sandrine Menguy, MD, PhD, CHU DE SAINT-ETIENNE

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: October 13, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: phytotherapy; Chronic Myeloid Leukemia; hematology; Tyrosine Kinase Inhibitor; drug interactions; targeted therapies; pharmaceutical conciliation; pharmaceutical intervention
• 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; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: 2021-0401; 2021-A00942-39 (Other Identifier: Agence Nationale de Sécurité du Médicament et des produits de santé)

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