Clinical trial NCT05753384: Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tyrosine Kinase Inhibitors
Chronic Myeloid Leukemia
Keywords: Characteristics of innate T cells
Lead sponsor: Poitiers University Hospital
Sponsor class: OTHER
First posted: 2023-03-03
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

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

Primary outcomes:
measure: 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).
timeFrame: 24 months after treatment discontinuation
Secondary outcomes:
measure: Difference in proportions (%) at randomization and 12 months post randomization, of innate CD8 T cells among total CD8 T cells
timeFrame: 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Chu Angers
city: Annecy
country: France
facility: Ch Annecy
city: Bayonne
country: France
facility: Ch Bayonne
city: Brest
country: France
facility: Chu Brest
city: Brive-la-Gaillarde
country: France
facility: CH Brive la Gaillarde
city: Chambéry
country: France
facility: Ch Chambery
city: Créteil
country: France
facility: CHI Creteil
city: La Rochelle
country: France
facility: Ch La Rochelle
city: Lille
country: France
facility: Chu Lille
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Mont-de-Marsan
country: France
facility: Ch Mont de Marsan
city: Nancy
country: France
facility: Chu Nancy
city: Nantes
country: France
facility: Chu Nantes
city: Nantes
country: France
facility: Hopital Prive Du Confluent
city: Poitiers
country: France
facility: Chu Poitiers
city: Périgueux
country: France
facility: Ch Perigueux
city: Toulouse
country: France
facility: Oncopole Toulouse
city: Tours
country: France
facility: Chu Tours
city: Versailles
country: France
facility: CH Versailles
Study officials:
References: