NCT01596114: EURO-SKI

European Stop Tyrosine Kinase Inhibitor Study

Completed Phase 3 Last updated 5 November 2021

What this trial tests

Phase 3 trial testing Stopping treatment with TKI in Chronic Myeloid Leukemia in 868 participants. Completed in 31 December 2019.

Timeline

30 May 2012

Primary endpoint
3 December 2014

31 December 2019

Quick facts

Lead sponsor	European LeukemiaNet
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	868
Start date	30 May 2012
Primary completion	3 December 2014
Estimated completion	31 December 2019
Sites	50 locations across Denmark, France, Finland, Netherlands, Greece, Sweden, Germany, Norway

Drugs / interventions tested

• Stopping treatment with TKI

Conditions studied

• Chronic Myeloid Leukemia — all drugs for Chronic Myeloid Leukemia →

Sponsor

European LeukemiaNet

Who can join

18 and older, any sex, with Chronic Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The EURO-SKI is a multicenter open label, uncontrolled trial estimating the persistence of molecular remission in Chronic Myeloid Leukemia (CML) patients after stopping Tyrosine Kinase Inhibitor (TKI). Main goal is the assessment of the duration of major molecular response (MMR) or better after stopping TKI therapy.

Secondary goals include:

* Identification of clinical and biological factors affecting the persistence of complete molecular remission after stopping TKI (e.g. level of Complete molecular remission (CMR), risk score, duration of TKI treatment, type of TKI pretreatment)
* Evaluation of quality of life (QoL) in patients stopping TKI
* Evaluation of medico-economic impact of stopping TKI
* Estimating the number of patients in CMR who are eligible for stopping TKI therapy by setting up a screening log
* Time to recovery of CMR There will be no randomised comparison. Based on the experience of the STIM trial (Mahon et al., Lancet Onc 2010) we expect an overall six-month molecular-relapse-free survival probability of at least 40%. An interim analysis will be performed after a pilot phase where 200 patients have been observed for at least six months. Formally, it is planned to test the null hypothesis H0: Six-month molecular relapse-free survival probability P ≤ 40% against the alternative hypothesis H1: Six-month molecular-relapse-free survival probability P \> 40%. Eligible are adult CML patients in chronic phase on TKI treatment in CMR for at least one year (\> 4 log reduction of BCR-ABL transcripts on IS, TKI treatment for at least 3 years, confirmed by a PCR within a standardized CMR laboratory). Clinical and biological monitoring will be performed during 3 years: Associated scientific projects are performed. Recruitment period: 2 years; follow up: 3 years. Planned patient recruitment in main phase: n=500

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial.
   Saussele S, Richter J, Guilhot J, Gruber FX, et al · · 2018 · cited 433× · PMID 29735299 · DOI 10.1016/s1470-2045(18)30192-x
2. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
   Ilander M, Olsson-Strömberg U, Schlums H, Guilhot J, et al · · 2017 · cited 192× · PMID 27890936 · DOI 10.1038/leu.2016.360
3. Treatment-free remission with first- and second-generation tyrosine kinase inhibitors.
   Cortes J, Rea D, Lipton JH. · · 2019 · cited 93× · PMID 30394563 · DOI 10.1002/ajh.25342
4. Treatment outcome in a population-based, 'real-world' cohort of patients with chronic myeloid leukemia.
   Geelen IGP, Thielen N, Janssen JJWM, Hoogendoorn M, et al · · 2017 · cited 43× · PMID 28860339 · DOI 10.3324/haematol.2017.174953
5. A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase.
   García-Gutiérrez V, Breccia M, Jabbour E, Mauro M, et al · · 2022 · cited 39× · PMID 35818053 · DOI 10.1186/s13045-022-01309-0
6. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities.
   Flis S, Chojnacki T. · · 2019 · cited 39× · PMID 30880916 · DOI 10.2147/dddt.s191303
7. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.
   Cuellar S, Vozniak M, Rhodes J, Forcello N, et al · · 2018 · cited 28× · PMID 28580869 · DOI 10.1177/1078155217710553
8. NK Cell Plasticity in Cancer.
   Liu S, Dhar P, Wu JD. · · 2019 · cited 26× · PMID 31546818 · DOI 10.3390/jcm8091492