European Stop Tyrosine Kinase Inhibitor Study (EURO-SKI)

This study is currently recruiting participants.
Verified March 2014 by European LeukemiaNet
Sponsor:
Information provided by (Responsible Party):
European LeukemiaNet
ClinicalTrials.gov Identifier:
NCT01596114
First received: May 8, 2012
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Chronic Myeloid Leukemia
Other: Stopping treatment with TKI
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukemia After Stopping TKI

Resource links provided by NLM:


Further study details as provided by European LeukemiaNet:

Primary Outcome Measures:
  • molecular relapse-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Overall and progression-free survival and the probabilities of a restart of TKI without prior molecular relapse

  • Treatment costs [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Saved treatment costs / country from the time off TKI therapy considering also the more frequent PCR monitoring

  • QoL [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Patient reported QoL and symptom burden over time

  • Time to recovery [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Analysing the time to recovery of CMR4 after loss of MMR


Estimated Enrollment: 500
Study Start Date: June 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01596114

Contacts
Contact: Susanne Saussele, PD Dr. +496213836966 susanne.saussele@medma.uni-heidelberg.de
Contact: Francois X Mahon, Prof 33 (0)5 57 57 10 10 Francois-Xavier.Mahon@u-bordeaux2.fr

  Show 50 Study Locations
Sponsors and Collaborators
European LeukemiaNet
Investigators
Principal Investigator: Susanne Saussele, Dr. Universitätsmedizin Mannheim, Universität Heidelberg
  More Information

No publications provided

Responsible Party: European LeukemiaNet
ClinicalTrials.gov Identifier: NCT01596114     History of Changes
Other Study ID Numbers: ELN-001, 2011-000440-22
Study First Received: May 8, 2012
Last Updated: March 17, 2014
Health Authority: Sweden: Medical Products Agency

Keywords provided by European LeukemiaNet:
TKI
CML
Stopping
chronic phase
in remission

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Tin Fluorides
Cariostatic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014