EURO-SKI: European Stop Tyrosine Kinase Inhibitor Study

Sponsor

European LeukemiaNet (Other)

Overall Status

Completed

CT.gov ID

NCT01596114

Collaborator

(none)

868

Enrollment

Locations

Arm

Actual Duration (Months)

17.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Other: Stopping treatment with TKI	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

868 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 30, 2012

Actual Primary Completion Date :

Dec 3, 2014

Actual Study Completion Date :

Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Other: Stopping treatment with TKI stopping until loss of MMR

Arm

Intervention/Treatment

Experimental: 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

Other: Stopping treatment with TKI

stopping until loss of MMR

Outcome Measures

Primary Outcome Measures

molecular relapse-free survival [3 years]
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))

Secondary Outcome Measures

Overall and progression-free survival [3 years]
Overall and progression-free survival and the probabilities of a restart of TKI without prior molecular relapse
Treatment costs [3 years]
Saved treatment costs / country from the time off TKI therapy considering also the more frequent PCR monitoring
QoL [3 years]
Patient reported QoL and symptom burden over time
Time to recovery [3 years]
Analysing the time to recovery of CMR4 after loss of MMR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Fakultní nemocnice	Brno	Czechia	625 00
2	Fakultní nemocnice Hradec Králové	Hradec Kralove	Czechia	50005
3	University Hospital Olomouc	Olomouc	Czechia	775 20
4	University Hospital Plzen	Plzen	Czechia	30460
5	Fakultni nemocnice Kralovske Vinohrady	Prague	Czechia	100 34
6	Ústav hematologie a krevní transfuze	Prague	Czechia	12820
7	Odense University Hospital	Odense	Denmark	5000
8	Helsinki University Central Hospital	Helsinki	Finland	00029 HUCH
9	CHU d'Angers	Angers	France	49933
10	Institut Bergonié	Bordeaux	France	33000
11	Université Victor Segalen	Bordeaux	France	33076
12	Hôpital André Mignot	Chesnay cedex	France	78157
13	Chu Estaing	Clermont Ferrand	France	63003
14	Hôpital Claude Huriez	Lille	France	59037
15	Hôpital Édouard Herriot	Lyon	France	69437
16	Institut Paoli-Calmettes (IPC)	Marseille	France	13273
17	Centre Hospitalier Universitaire (CHU) de Nantes	Nantes	France	44093
18	Hôpital de l'Archet	Nice	France	06200
19	Hôpital Saint-Louis	Paris cedex 10	France	75475
20	Hôpital Necker-Enfants Malades	Paris Cedex 15	France	75743
21	Hopital de la Milétrie, Centre Hospitalier Universitaire (CHU) de Poitiers	Poitiers	France	86021
22	Hôpital Pontchaillou	Rennes	France	35033
23	Hôpital Purpan	Toulouse	France	31059
24	CHU de Tours	Tours	France	37044
25	Hôpital de Brabois	Vandoeuvre-lès-Nancy	France	54511
26	Uniklinik RWTH	Aachen	Germany	52074
27	Universitätsklinikum	Bonn	Germany	53105
28	Klinikum	Chemnitz	Germany	09113
29	Universitätsklinikum	Jena	Germany	07747
30	Klinikum Kempten-Oberallgäu	Kempten	Germany	87439
31	Universitätsmedizin Mannheim, Universität Heidelberg	Mannheim	Germany	68163
32	Universitätsklinikum Giessen und Marburg GmbH	Marburg	Germany	35033
33	MVZ Klinikum Straubing GmbH	Straubing	Germany	94315
34	University of Athens, Society of Hematology	Athens	Greece	11526
35	VU Academic Medical Center	Amsterdam	Netherlands	1007 MB
36	Albert Schweitzer Hospital	Dordrecht	Netherlands	3300
37	Oslo universitetssykehus HF Rikshospitalet	Oslo	Norway	0372
38	Stavanger University Hospital	Stavanger	Norway	4068
39	University Hospital of Northern Norway	Tromsø	Norway	9038
40	Norwegian University of Science and Technology	Trondheim	Norway	7489
41	Instituto Português de Oncologia Francisco Gentil	Lisboa	Portugal	1099-023
42	Karoliniska Univ hospital Huddinge	Huddinge	Sweden	141 86
43	Univ hospital Linköping	Linköping	Sweden	581 85
44	Sunderby hospital	Luleå	Sweden	971 80
45	Lunds Universitet	Lund	Sweden	221 85
46	Karoliniska Univ sjh Solna	Stockholm	Sweden	171 76
47	Länssj Sundsvall	Sundsvall	Sweden	851 86
48	Norrlands Univ hospital	Umeå	Sweden	901 85
49	Uppsala University hospital	Uppsala	Sweden	751 85
50	Univ hospital Örebro	Örebro	Sweden	701 85