De-escalation Strategy of Tyrosine Kinase Inhibitors Before Treatment Discontinuation in Patients With Chronic Myeloid Leukemia

Summary

The goal of this clinical trial is to learn if a 1-year dose-reduction strategy with tyrosine kinase inhibitors (TKIs) - before complete discontinuation - works to improve treatment-free remission in adults with chronic-phase chronic myeloid leukaemia (CML) who have already achieved stable deep molecular response and are eligible to stop therapy. It will also learn about the safety of this gradual reduction approach. The main questions it aims to answer are: Does the dose-reduction strategy lead to a higher 2-year molecular relapse-free survival rate (maintaining major molecular response, BCR-ABL1 ≤0.1%) compared with immediate TKI discontinuation? What medical problems (adverse events) do participants experience during and after dose reduction, and how do they differ from those in the direct-stop group? Researchers will compare the dose-reduction group (reduced daily TKI for 12 months, then 1-year follow-up) with the direct-discontinuation group (immediate stop, 2-year follow-up) to see whether gradual reduction is superior in preserving molecular remission. In addition, they will compare the changes in T-cell subsets between the two groups to explore immune mechanisms that may influence treatment-free remission. Participants will: Be randomly assigned to either dose reduction or immediate discontinuation; Take reduced TKI (or no drug) daily for 1 year, followed by 1-year observation (total 24 months); Visit the clinic every 2 months for the first 6 months, then every 3 months thereafter, for physical exams, blood tests, molecular monitoring (BCR-ABL1 PCR), and ECG; Have T-cell subsets measured by flow cytometry at months 3, 6, 12, and 24; Complete quality-of-life questionnaires (EORTC QLQ-CML24) at baseline and at months 3, 6, 12, and 24; Report all adverse events; if MMR is lost, they must restart full-dose TKI and be monitored monthly until remission is regained;

Timeline

Start

2026-09-09

Primary completion

2030-07-31

Completion

2030-12-31

Publications

• Background Chen Y, Xu N, Yang Y, Liu Z, Xue M, Meng L, He Q, Chen C, Zeng Q, Zhu H, Du X, Zou J, He W, Guo J, Chen S, Yuan G, Wu H, Hong M, Cheng F, Liu B, Zhang Y, Li W. Quality-of-life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia. Cancer Med. 2023 Aug;12(16):17239-17252. doi: 10.1002/cam4.6296. Epub 2023 Jul 6.
• Background Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, Janssen JJWM, Mayer J, Koskenvesa P, Panayiotidis P, Olsson-Stromberg U, Martinez-Lopez J, Rousselot P, Vestergaard H, Ehrencrona H, Kairisto V, Machova Polakova K, Muller MC, Mustjoki S, Berger MG, Fabarius A, Hofmann WK, Hochhaus A, Pfirrmann M, Mahon FX; EURO-SKI investigators. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018 Jun;19(6):747-757. doi: 10.1016/S1470-2045(18)30192-X. Epub 2018 May 4.
• Background Luo J, Du X, Lou J, Wu J, Ma L, Huang J, Wang L, Tu C, Liu Z, Chen L, Tan Y, Luo D, Liang H, Yin C, Cao R, Zhou X, Liu Q, Liu X, Xu N. De-escalation or discontinuation of tyrosine kinase inhibitor in patients with chronic myeloid leukemia: A multicentral, open-label, prospective trial in China. EJHaem. 2022 Sep 19;3(4):1220-1230. doi: 10.1002/jha2.550. eCollection 2022 Nov.
• Background Clark RE, Polydoros F, Apperley JF, Milojkovic D, Rothwell K, Pocock C, Byrne J, de Lavallade H, Osborne W, Robinson L, O'Brien SG, Read L, Foroni L, Copland M. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019 Jul;6(7):e375-e383. doi: 10.1016/S2352-3026(19)30094-8. Epub 2019 Jun 12.

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