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Chronic Myeloid LeukemiaPhase 3EURO-SKINCT01596114

European Stop Tyrosine Kinase Inhibitor Study

A Phase 3 study testing Stopping treatment with TKI in people with Chronic Myeloid Leukemia, run by European LeukemiaNet at 50 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia
What is being tested?
Stopping treatment with TKI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
868 participants
Where
50 sitesin 10 countries
Study dates
30 May 2012to 31 Dec 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • CML in CP under treatment with TKI in first line or in second line because of toxicity to first line TKI or with TKI in combination
  • Duration of TKI treatment before enrolment at least 3 years
  • At least complete molecular remission MR4
  • Before inclusion confirmation of CMR4 through a EUTOS-CMR laboratory
  • Baseline data and documentation on treatment before study entry available
  • Both sexes but fertile women only if using effective contraceptive
  • Health insurance coverage
  • 18 years or older

Who cannot join

  • Under 18 years old
  • Hospitalized patients without ability to give informed consent
  • Adults under law protection or without ability to consent
  • Previous or planned allogeneic stem cell transplantation

Trial locations and contacts

50 sites in 10 countries.

50 sites in 10 countries

France17 sites

  • CHU d'Angers

    Angers, 49933

  • Institut Bergonié

    Bordeaux, 33000

  • Université Victor Segalen

    Bordeaux, 33076

  • Hôpital André Mignot

    Chesnay, 78157

  • Chu Estaing

    Clermont-Ferrand, 63003

  • Hôpital Claude Huriez

    Lille, 59037

  • Hôpital Édouard Herriot

    Lyon, 69437

  • Institut Paoli-Calmettes (IPC)

    Marseille, 13273

  • Centre Hospitalier Universitaire (CHU) de Nantes

    Nantes, 44093

  • Hôpital de l'Archet

    Nice, 06200

  • Hôpital Saint-Louis

    Paris, 75475

  • Hôpital Necker-Enfants Malades

    Paris, 75743

  • Hopital de la Milétrie, Centre Hospitalier Universitaire (CHU) de Poitiers

    Poitiers, 86021

  • Hôpital Pontchaillou

    Rennes, 35033

  • Hôpital Purpan

    Toulouse, 31059

  • CHU de Tours

    Tours, 37044

  • Hôpital de Brabois

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Sweden9 sites

  • Karoliniska Univ hospital Huddinge

    Huddinge, 141 86

  • Univ hospital Linköping

    Linköping, 581 85

  • Sunderby hospital

    Luleå, 971 80

  • Lunds Universitet

    Lund, 221 85

  • Univ hospital Örebro

    Örebro, 701 85

  • Karoliniska Univ sjh Solna

    Stockholm, 171 76

  • Länssj Sundsvall

    Sundsvall, 851 86

  • Norrlands Univ hospital

    Umeå, 901 85

  • Uppsala University hospital

    Uppsala, 751 85

Other trials in Sweden

Germany8 sites

  • Uniklinik RWTH

    Aachen, 52074

  • Universitätsklinikum

    Bonn, 53105

  • Klinikum

    Chemnitz, 09113

  • Universitätsklinikum

    Jena, 07747

  • Klinikum Kempten-Oberallgäu

    Kempten, 87439

  • Universitätsmedizin Mannheim, Universität Heidelberg

    Mannheim, 68163

  • Universitätsklinikum Giessen und Marburg GmbH

    Marburg, 35033

  • MVZ Klinikum Straubing GmbH

    Straubing, 94315

Other trials in Germany

Czechia6 sites

  • Fakultní nemocnice

    Brno, 625 00

  • Fakultní nemocnice Hradec Králové

    Hradec Králové, 50005

  • University Hospital Olomouc

    Olomouc, 775 20

  • University Hospital Plzen

    Pilsen, 30460

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 34

  • Ústav hematologie a krevní transfuze

    Prague, 12820

Other trials in Czechia

Norway4 sites

  • Oslo universitetssykehus HF Rikshospitalet

    Oslo, 0372

  • Stavanger University Hospital

    Stavanger, 4068

  • University Hospital of Northern Norway

    Tromsø, 9038

  • Norwegian University of Science and Technology

    Trondheim, 7489

Other trials in Norway

Netherlands2 sites

  • VU Academic Medical Center

    Amsterdam, 1007 MB

  • Albert Schweitzer Hospital

    Dordrecht, 3300

Other trials in Netherlands

Denmark1 site

  • Odense University Hospital

    Odense, 5000

Other trials in Denmark

Finland1 site

  • Helsinki University Central Hospital

    Helsinki, 00029 HUCH

Other trials in Finland

Greece1 site

  • University of Athens, Society of Hematology

    Athens, 11526

Other trials in Greece

Portugal1 site

  • Instituto Português de Oncologia Francisco Gentil

    Lisbon, 1099-023

Other trials in Portugal

About this study

Official title: Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukemia After Stopping TKI

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
Being tested
Stopping treatment with TKI
Keywords
TKI, CML, Stopping, chronic phase, in remission
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stopping treatment with TKIOther

    stopping until loss of MMR

Study groups in NCT01596114
Study groupRoleWhat they receive
Stop treatmentExperimentalTKI treatment will be stopped in CML patients with very deep molecular responses for at least one year and at least 3 years TKI treatment
Receives: Other: Stopping treatment with TKI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. molecular relapse-free survival

    Evaluation of molecular relapse-free survival after stopping TKI (survival without molecular relapse defined by BCR-ABL1 > 0.1% on the IS at one time point (loss of major molecular response, MMR))

    Measured: 3 years

Secondary outcomes (4)

  1. Overall and progression-free survival

    Overall and progression-free survival and the probabilities of a restart of TKI without prior molecular relapse

    Measured: 3 years

  2. Treatment costs

    Saved treatment costs / country from the time off TKI therapy considering also the more frequent PCR monitoring

    Measured: 3 years

  3. QoL

    Patient reported QoL and symptom burden over time

    Measured: 3 years

  4. Time to recovery

    Analysing the time to recovery of CMR4 after loss of MMR

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2012 (estimated)
  2. Study start30 May 2012
  3. Primary completion3 Dec 2014
  4. Study completion31 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
868 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01596114
Sponsor's protocol ID
ELN-001
Other IDs
2011-000440-22
Acronym
EURO-SKI
Status last verified
Oct 2021
First submitted
8 May 2012
Last updated
5 Nov 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Richter J, Lubking A, Soderlund S, Lotfi K, Markevarn B, Sjalander A, Stenke L, Deneberg S, Ahlstrand E, Myhr-Eriksson K, Panayiotidis P, Gedde-Dahl T, Zackova D, Mayer J, Olsson-Stromberg U, Mahon FX, Saussele S, Hjorth-Hansen H, Koskenvesa P. Molecular status 36 months after TKI discontinuation in CML is highly predictive for subsequent loss of MMR-final report from AFTER-SKI. Leukemia. 2021 Aug;35(8):2416-2418. doi: 10.1038/s41375-021-01173-w. Epub 2021 Feb 15. No abstract available.

    PubMed 33589755

  • Soderlund S, Persson I, Ilander M, Guilhot J, Hjorth-Hansen H, Koskenvesa P, Richter J, Saussele S, Mustjoki S, Olsson-Stromberg U. Plasma proteomics of biomarkers for inflammation or cancer cannot predict relapse in chronic myeloid leukaemia patients stopping tyrosine kinase inhibitor therapy. Leuk Res. 2020 Mar;90:106310. doi: 10.1016/j.leukres.2020.106310. Epub 2020 Jan 23.

    PubMed 32058176

  • Bouillon AS, Ventura Ferreira MS, Awad SA, Richter J, Hochhaus A, Kunzmann V, Dengler J, Janssen J, Ossenkoppele G, Westerweel PE, Te Boekhorst PAW, Mahon FX, Hjorth-Hansen H, Isfort S, Fioretos T, Hummel S, Schemionek M, Wilop S, Koschmieder S, Saussele S, Mustjoki S, Beier F, Brummendorf TH. Telomere shortening correlates with leukemic stem cell burden at diagnosis of chronic myeloid leukemia. Blood Adv. 2018 Jul 10;2(13):1572-1579. doi: 10.1182/bloodadvances.2018017772.

    PubMed 29980572

  • Schutz C, Inselmann S, Saussele S, Dietz CT, Mu Ller MC, Eigendorff E, Brendel CA, Metzelder SK, Bru Mmendorf TH, Waller C, Dengler J, Goebeler ME, Herbst R, Freunek G, Hanzel S, Illmer T, Wang Y, Lange T, Finkernagel F, Hehlmann R, Huber M, Neubauer A, Hochhaus A, Guilhot J, Xavier Mahon F, Pfirrmann M, Burchert A. Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML. Leukemia. 2017 Apr;31(4):829-836. doi: 10.1038/leu.2017.9. Epub 2017 Jan 11.

    PubMed 28074067

  • 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.

    PubMed 29735299

  • Ilander M, Olsson-Stromberg U, Schlums H, Guilhot J, Bruck O, Lahteenmaki H, Kasanen T, Koskenvesa P, Soderlund S, Hoglund M, Markevarn B, Sjalander A, Lotfi K, Dreimane A, Lubking A, Holm E, Bjoreman M, Lehmann S, Stenke L, Ohm L, Gedde-Dahl T, Majeed W, Ehrencrona H, Koskela S, Saussele S, Mahon FX, Porkka K, Hjorth-Hansen H, Bryceson YT, Richter J, Mustjoki S. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia. Leukemia. 2017 May;31(5):1108-1116. doi: 10.1038/leu.2016.360. Epub 2016 Nov 28.

    PubMed 27890936

  • Rinaldetti S, Pfirrmann M, Manz K, Guilhot J, Dietz C, Panagiotidis P, Spiess B, Seifarth W, Fabarius A, Muller M, Pagoni M, Dimou M, Dengler J, Waller CF, Brummendorf TH, Herbst R, Burchert A, Janbetaen C, Goebeler ME, Jost PJ, Hanzel S, Schafhausen P, Prange-Krex G, Illmer T, Janzen V, Klausmann M, Eckert R, Buschel G, Kiani A, Hofmann WK, Mahon FX, Saussele S. Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial. Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):266-271. doi: 10.1016/j.clml.2018.02.004. Epub 2018 Feb 8.

    PubMed 29510895

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Stopping treatment with TKI in people with Chronic Myeloid Leukemia, run by European LeukemiaNet at 50 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in France, Sweden, Germany, Czechia, Norway and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

molecular relapse-free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01596114, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.

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