European Stop Tyrosine Kinase Inhibitor Study

NCT ID: NCT01596114

Last Updated: 2021-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

868 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-30

Study Completion Date

2019-12-31

Brief Summary

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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

Detailed Description

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Conditions

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Chronic Myeloid Leukemia

Keywords

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TKI CML Stopping chronic phase in remission

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stop treatment

TKI treatment will be stopped in CML patients with very deep molecular responses for at least one year and at least 3 years TKI treatment

Group Type EXPERIMENTAL

Stopping treatment with TKI

Intervention Type OTHER

stopping until loss of MMR

Interventions

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Stopping treatment with TKI

stopping until loss of MMR

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European LeukemiaNet

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanne Saussele, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitätsmedizin Mannheim, Universität Heidelberg

Locations

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Fakultní nemocnice

Brno, , Czechia

Site Status

Fakultní nemocnice Hradec Králové

Hradec Králové, , Czechia

Site Status

University Hospital Olomouc

Olomouc, , Czechia

Site Status

University Hospital Plzen

Pilsen, , Czechia

Site Status

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

Site Status

Ústav hematologie a krevní transfuze

Prague, , Czechia

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

CHU d'Angers

Angers, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

Université Victor Segalen

Bordeaux, , France

Site Status

Hôpital André Mignot

Chesnay, , France

Site Status

Chu Estaing

Clermont-Ferrand, , France

Site Status

Hôpital Claude Huriez

Lille, , France

Site Status

Hôpital Édouard Herriot

Lyon, , France

Site Status

Institut Paoli-Calmettes (IPC)

Marseille, , France

Site Status

Centre Hospitalier Universitaire (CHU) de Nantes

Nantes, , France

Site Status

Hôpital de l'Archet

Nice, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Necker-Enfants Malades

Paris, , France

Site Status

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

Poitiers, , France

Site Status

Hôpital Pontchaillou

Rennes, , France

Site Status

Hôpital Purpan

Toulouse, , France

Site Status

CHU de Tours

Tours, , France

Site Status

Hôpital de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Uniklinik RWTH

Aachen, , Germany

Site Status

Universitätsklinikum

Bonn, , Germany

Site Status

Klinikum

Chemnitz, , Germany

Site Status

Universitätsklinikum

Jena, , Germany

Site Status

Klinikum Kempten-Oberallgäu

Kempten, , Germany

Site Status

Universitätsmedizin Mannheim, Universität Heidelberg

Mannheim, , Germany

Site Status

Universitätsklinikum Giessen und Marburg GmbH

Marburg, , Germany

Site Status

MVZ Klinikum Straubing GmbH

Straubing, , Germany

Site Status

University of Athens, Society of Hematology

Athens, , Greece

Site Status

VU Academic Medical Center

Amsterdam, , Netherlands

Site Status

Albert Schweitzer Hospital

Dordrecht, , Netherlands

Site Status

Oslo universitetssykehus HF Rikshospitalet

Oslo, , Norway

Site Status

Stavanger University Hospital

Stavanger, , Norway

Site Status

University Hospital of Northern Norway

Tromsø, , Norway

Site Status

Norwegian University of Science and Technology

Trondheim, , Norway

Site Status

Instituto Português de Oncologia Francisco Gentil

Lisbon, , Portugal

Site Status

Karoliniska Univ hospital Huddinge

Huddinge, , Sweden

Site Status

Univ hospital Linköping

Linköping, , Sweden

Site Status

Sunderby hospital

Luleå, , Sweden

Site Status

Lunds Universitet

Lund, , Sweden

Site Status

Univ hospital Örebro

Örebro, , Sweden

Site Status

Karoliniska Univ sjh Solna

Stockholm, , Sweden

Site Status

Länssj Sundsvall

Sundsvall, , Sweden

Site Status

Norrlands Univ hospital

Umeå, , Sweden

Site Status

Uppsala University hospital

Uppsala, , Sweden

Site Status

Countries

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Czechia Denmark Finland France Germany Greece Netherlands Norway Portugal Sweden

References

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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.

Reference Type BACKGROUND
PMID: 33589755 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32058176 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29980572 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28074067 (View on PubMed)

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.

Reference Type RESULT
PMID: 29735299 (View on PubMed)

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.

Reference Type RESULT
PMID: 27890936 (View on PubMed)

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.

Reference Type RESULT
PMID: 29510895 (View on PubMed)

Other Identifiers

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2011-000440-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ELN-001

Identifier Type: -

Identifier Source: org_study_id