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

NCT05753384 | Active Not Recruiting Phase 3

• 1 other identifier: AITIK
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 20

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

Keywords

Characteristics of innate T cells

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  12 months

Study Arms (2)

continued treatment with TKI at 50% dose reduction

EXPERIMENTAL

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

Drug: treatment of TKI in CML

continuation of TKI treatment without dose change

ACTIVE COMPARATOR

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

Drug: treatment of TKI in CML

Interventions

treatment of TKI in CML 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 50% dose reduction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient ≥ 18 year-old.
• Diagnosis of chronic phase CML according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2 or e14a2)
• 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
• Protected person
• Pregnant women or women of childbearing age without appropriate contraceptive measures

Sponsors & Collaborators

• Poitiers University Hospital: lead

Study Sites (20)

Chu Angers

Angers, France

Location

Ch Annecy

Annecy, France

Location

Ch Bayonne

Bayonne, France

Location

Chu Brest

Brest, France

Location

CH Brive la Gaillarde

Brive-la-Gaillarde, France

Location

Ch Chambery

Chambéry, France

Location

CHI Creteil

Créteil, France

Location

Ch La Rochelle

La Rochelle, France

Location

Chu Lille

Lille, France

Location

CHU Limoges

Limoges, France

Location

Centre Léon Bérard

Lyon, France

Location

Ch Mont de Marsan

Mont-de-Marsan, France

Location

Chu Nancy

Nancy, France

Location

Chu Nantes

Nantes, France

Location

Hopital Prive Du Confluent

Nantes, France

Location

Ch Perigueux

Périgueux, France

Location

Chu Poitiers

Poitiers, France

Location

Oncopole Toulouse

Toulouse, France

Location

Chu Tours

Tours, France

Location

CH Versailles

Versailles, France

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: March 3, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

FR (20)