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

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.

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Key information

Conditions

Tyrosine Kinase Inhibitors Bone Marrow Diseases Chronic Disease Chronic Myeloid Leukemia Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Chu Angers, Angers, France

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

treatment of TKI in CML

Drug

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

Primary outcomes

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).

Time frame: 24 months after treatment discontinuation

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.

Secondary outcomes

Difference in proportions (%) at randomization and 12 months post randomization, of innate CD8 T cells among total CD8 T cells

Time frame: 12 months

Sponsors and collaborators

Lead sponsor

Poitiers University Hospital

Other

Registry information

Official study 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

Important dates

Study start: 2023
Primary completion: 2028
Study completion: 2029
First posted: Mar 3, 2023
Registry last updated: Apr 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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