Clinical trial NCT02897245: A Study for Tyrosine Kinase Inhibitors Discontinuation
Official title: An Observational Study for CML Patients Who Discontinued Tyrosine Kinase Inhibitors Intentionally After Achieving a Deep Molecular Response
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Leukemia
Keywords: Myelogenous
Chronic
BCR-ABL Positive
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2016-09-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: These are patients with chronic myeloid leukemia treated with a tyrosine kinase inhibitor for which an intentional discontinuation was made since 2007 outside the framework of a prospective study

Brief summary: Treatment of Chronic Myeloid Leukemia (CML) has been revolutionized by the use of tyrosine kinase inhibitors including imatinib mesylate (Gleevec, Novartis Laboratories). Two other inhibitors of the BCR-ABL kinase are currently on the market in France, nilotinib (Tasigna®, Novartis Laboratories) in the first and second-line treatment and dasatinib (SPRYCEL®, Bristol-Myers Squibb Laboratories) in second line. Achieving a complete molecular response (CMR) in patients with Chronic Myeloid Leukemia (CML) treated with tyrosine kinase inhibitors may be currently regarded as the ultimate level of reduction of residual disease. The pilot Stop Imatinib study has opened the way for a french prospective study of stopping imatinib, the STIM study. The results of the STIM study showed that almost 60% of patients exhibited molecular relapse, most frequently within the first 6 months after discontinuation. The parameters that are statistically associated with the loss of complete molecular response are the Sokal score at diagnosis and the total duration of treatment with imatinib. Criteria to define molecular relapse in treatment free remission patients are not well defined and validated. The aim of the study is to validate the loss of major molecular response as a robust criteria for TKI resumption. The patient's population will be CML patients who are offered to discontinue therapy outside the STIM strial.


Eligibility criteria: Inclusion Criteria:

* Patient with Chronic Myelogenous leukemia
* mors than 18 years old
* intentionally stop treatment by tyrosine kinase inhibitor

Exclusion Criteria:

* inclusion in a prospective study
* non intentionally stop (adverse event)
* Stop for disease progression
* Death patients

Primary outcomes:
measure: Survival without loss of molecular response major (RMM BCR-ABL / ABL IS ≤ 0.1%)
timeFrame: 2 years
Secondary outcomes:
measure: Treatment free survival molecular evolution in treatment discontinuation
timeFrame: 2 years
measure: Progression free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: The rate of deep molecular response after restarting TKIs kinase
timeFrame: 2 years
measure: Withdrawal syndrome
timeFrame: 2 years
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: CH Versailles
Study officials:
References:
citation: Rousselot P, Loiseau C, Delord M, Cayuela JM, Spentchian M. Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission. Blood Adv. 2020 Jul 14;4(13):3034-3040. doi: 10.1182/bloodadvances.2020001772.