Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System

NCT ID: NCT05753384

Last Updated: 2024-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2029-12-01

Brief Summary

Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. The ability to permanently stop treatment with TKI has thus become a major goal in CML to prevent the occurrence of adverse events, improve quality of life and reduce the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now remains to be demonstrated in a comparative prospective study that a strategy of de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR results. At the same time, it is possible to reduce adverse reactions and improve the quality of life of patients. In this context, the investigator propose to conduct a randomized clinical trial including CML patients, allowing to compare the results of TFR at 24 months between a sudden stop of treatment after a maintenance phase of dosage for 12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before stopping. A secondary immunological translational objective of this project will be to compare the quantitative and qualitative evolution of innate CD8 T cells between the 2 arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a predictive innate CD8 T cells blood signature at the time of stopping treatment of a successful TFR in both arms.

Conditions

Tyrosine Kinase Inhibitors; Chronic Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

continued treatment with TKI at 50% dose reduction

continued treatment with TKI at 50% dose reduction compared to dosing received at randomization and then stopped treatment 12 months after randomization

Group Type: EXPERIMENTAL

treatment of TKI in CML

Intervention Type: DRUG

continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

continuation of TKI treatment without dose change

continued treatment with TKI at same dose compared to dosing received at randomization and then stopped treatment 12 months after randomization

Group Type: ACTIVE_COMPARATOR

treatment of TKI in CML

Intervention Type: DRUG

continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

Interventions

treatment of TKI in CML

continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient ≥ 18 year-old.
• Diagnosis of chronic phase CML according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2 or e14a2)
• Duration of treatment by Imatinib ≥ 4 years / ITK2G ≥ 3 years /Imatinib and ITK2G ≥ 4 years and no change of TKI or decrease in dosage in the last 6 months prior to inclusion
• Deep Molecular Response (DMR) duration ≥ 1 year
• Absence of contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations nd the PCR of each TKI:

Imatinib (≥ 300 mg/j) Dasatinib (≥ 50 mg/j) Nilotinib (≥ 300 mg/j) Bosutinib (≥ 200 mg/j)

• Patient not participating in another interventional study for the duration of the interventional study
• Sexually active men should use effective contraception when taking Dasatinib
• Having an health insurance
• Having signed the consent form

• Patients with progressive severe pathology of poor prognosis immediately compromising participation in the entire study and/or with uncontrolled chronic pathology
• ECOG ≥ 3
• Prior resistance to TKI
• Patients who have already experienced an attempt of TKI cessation
• Patients with a malignant tumour that has been treated with chemotherapy within 2 months of inclusion or undergoing chemotherapy or that will be treated with post-inclusion chemotherapy
• Protected person
• Pregnant women or women of childbearing age without appropriate contraceptive measures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Poitiers University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Chu Angers

Angers, , France

Site Status: RECRUITING

Ch Annecy

Annecy, , France

Site Status: ACTIVE_NOT_RECRUITING

Ch Bayonne

Bayonne, , France

Site Status: RECRUITING

Chu Brest

Brest, , France

Site Status: RECRUITING

CH Brive la Gaillarde

Brive-la-Gaillarde, , France

Site Status: RECRUITING

Ch Chambery

Chambéry, , France

Site Status: ACTIVE_NOT_RECRUITING

CHI Creteil

Créteil, , France

Site Status: RECRUITING

Ch La Rochelle

La Rochelle, , France

Site Status: RECRUITING

Chu Lille

Lille, , France

Site Status: RECRUITING

CHU Limoges

Limoges, , France

Site Status: RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status: RECRUITING

Ch Mont de Marsan

Mont-de-Marsan, , France

Site Status: RECRUITING

Chu Nancy

Nancy, , France

Site Status: ACTIVE_NOT_RECRUITING

Chu Nantes

Nantes, , France

Site Status: RECRUITING

Hopital Prive Du Confluent

Nantes, , France

Site Status: ACTIVE_NOT_RECRUITING

Ch Perigueux

Périgueux, , France

Site Status: RECRUITING

Chu Poitiers

Poitiers, , France

Site Status: RECRUITING

Oncopole Toulouse

Toulouse, , France

Site Status: RECRUITING

Chu Tours

Tours, , France

Site Status: RECRUITING

CH Versailles

Versailles, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Emilie Cayssials-Caylus, Dr

Role: CONTACT

emilie.cayssials@chu-poitiers.fr

c

Facility Contacts

Corentin ORVAIN, Dr

Role: primary

Fréderic BAUDUER, Dr

Role: primary

Jean Christophe IANOTTO, Dr

Role: primary

Stéphane Girault, Dr

Role: primary

Lydia ROY, Dr

Role: primary

Emmanuel FLECK, Dr

Role: primary

Valerie COITEUX, Dr

Role: primary

Amélie PENOT, Dr

Role: primary

Franck NICOLINI, Dr

Role: primary

Samia MADENE HAROUNE, Dr

Role: primary

Viviane DUBRUILLE, Dr

Role: primary

Claire CALMETTE, Dr

Role: primary

José Miguel TORREGROSA DIAZ, Dr

Role: primary

Francoise HUGUET, Dr

Role: primary

Antoine MACHET, Dr

Role: primary

Philippe ROUSSELOT, Dr

Role: primary

Other Identifiers

AITIK

Identifier Type: -

Identifier Source: org_study_id