European Stop Tyrosine Kinase Inhibitor Study

Study Overview
=================
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

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

Conditions
-----------------
Chronic Myeloid Leukemia

Intervention / Treatment
-----------------
* Other: Stopping treatment with TKI


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stop treatment<br>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<br>* stopping until loss of MMR<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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)) | 3 years | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TKI, CML, Stopping, chronic phase, in remission