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

Chronic Myeloid Leukemia Clinical Trial

Official title:

Discontinuation of TyrosIne Kinase Inhibitors (ITK) in Chronic Myeloid Leukemia (LMC) and Impact on the Immune System: a Randomized Comparative Study of Two Therapeutic Strategies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05753384
• Other study ID #: AITIK
• Status: Recruiting
• Phase: Phase 3
• Start date: December 1, 2023
• Est. completion date: December 1, 2029

Study information

• Verified date: March 2024
• Source: Poitiers University Hospital
• Contact: Emilie Cayssials-Caylus, Dr
• Phone: c
• Email: emilie.cayssials[@]chu-poitiers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 1, 2029
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Non-Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• treatment of TKI in CML
continued treatment with TKI at randomization a then stopped treatment 12 months after randomization

Locations

Country	Name	City	State
France	Chu Angers	Angers
France	Ch Bayonne	Bayonne
France	Chu Brest	Brest
France	CHI Creteil	Créteil
France	Ch La Rochelle	La Rochelle
France	Chu Lille	Lille
France	CHU Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	Ch Mont de Marsan	Mont-de-Marsan
France	Chu Nantes	Nantes
France	Ch Perigueux	Périgueux
France	Chu Poitiers	Poitiers
France	Oncopole Toulouse	Toulouse
France	Chu Tours	Tours
France	CH Versailles	Versailles

Sponsors (1)

Lead Sponsor	Collaborator
Poitiers University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients.Treatment-Free Remission (TFR) is defined as patients with Major Molecular Response (MMR) or better (BCR-ABL level = 0.1% IS).	Percentage of patients in treatment free Remission (TFR) 24 months after treatment discontinuation in patients is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL level = 0.1% IS) on the total number of patients.	24 months after treatment discontinuation
Secondary	Difference in proportions (%) at randomization and 12 months post randomization, of innate CD8 T cells among total CD8 T cells		12 months