Trial Title:
Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System
NCT ID:
NCT05753384
Condition:
Tyrosine Kinase Inhibitors
Chronic Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Conditions: Keywords:
Characteristics of innate T cells
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
treatment of TKI in CML
Description:
continued treatment with TKI at randomization a then stopped treatment 12 months after
randomization
Arm group label:
continuation of TKI treatment without dose change
Arm group label:
continued treatment with TKI at 50% dose reduction
Summary:
Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of
chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack
of cure, is frequently associated with moderate, chronic and sometimes severe adverse
effects. The ability to permanently stop treatment with TKI has thus become a major goal
in CML to prevent the occurrence of adverse events, improve quality of life and reduce
the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now
remains to be demonstrated in a comparative prospective study that a strategy of
de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR
results. At the same time, it is possible to reduce adverse reactions and improve the
quality of life of patients. In this context, the investigator propose to conduct a
randomized clinical trial including CML patients, allowing to compare the results of TFR
at 24 months between a sudden stop of treatment after a maintenance phase of dosage for
12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before
stopping. A secondary immunological translational objective of this project will be to
compare the quantitative and qualitative evolution of innate CD8 T cells between the 2
arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a
predictive innate CD8 T cells blood signature at the time of stopping treatment of a
successful TFR in both arms.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient ≥ 18 year-old.
- Diagnosis of chronic phase CML according to WHO 2016 criteria with a typical
BCR::ABL1 rearrangement (e13a2 or e14a2)
- Duration of treatment by Imatinib ≥ 4 years / ITK2G ≥ 3 years /Imatinib and ITK2G ≥
4 years and no change of TKI or decrease in dosage in the last 6 months prior to
inclusion
- Deep Molecular Response (DMR) duration ≥ 1 year
- Absence of contraindication to the continuation of the same TKI for 12 months at the
same dosage according to international recommendations nd the PCR of each TKI:
Imatinib (≥ 300 mg/j) Dasatinib (≥ 50 mg/j) Nilotinib (≥ 300 mg/j) Bosutinib (≥ 200 mg/j)
- Patient not participating in another interventional study for the duration of the
interventional study
- Sexually active men should use effective contraception when taking Dasatinib
- Having an health insurance
- Having signed the consent form
Non-Inclusion Criteria:
- Patients with progressive severe pathology of poor prognosis immediately
compromising participation in the entire study and/or with uncontrolled chronic
pathology
- ECOG ≥ 3
- Prior resistance to TKI
- Patients who have already experienced an attempt of TKI cessation
- Patients with a malignant tumour that has been treated with chemotherapy within 2
months of inclusion or undergoing chemotherapy or that will be treated with
post-inclusion chemotherapy
- Protected person
- Pregnant women or women of childbearing age without appropriate contraceptive
measures
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Chu Angers
Address:
City:
Angers
Country:
France
Status:
Recruiting
Contact:
Last name:
Corentin ORVAIN, Dr
Investigator:
Last name:
Corentin ORVAIN, Dr
Email:
Principal Investigator
Facility:
Name:
Ch Annecy
Address:
City:
Annecy
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Ch Bayonne
Address:
City:
Bayonne
Country:
France
Status:
Recruiting
Contact:
Last name:
Fréderic BAUDUER, Dr
Investigator:
Last name:
Fréderic BAUDUER, Dr
Email:
Principal Investigator
Facility:
Name:
Chu Brest
Address:
City:
Brest
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean Christophe IANOTTO, Dr
Investigator:
Last name:
Jean christophe IANOTTO, Dr
Email:
Principal Investigator
Facility:
Name:
CH Brive la Gaillarde
Address:
City:
Brive-la-Gaillarde
Country:
France
Status:
Recruiting
Contact:
Last name:
Stéphane Girault, Dr
Investigator:
Last name:
Stéphane Girault, Dr
Email:
Principal Investigator
Facility:
Name:
Ch Chambery
Address:
City:
Chambéry
Country:
France
Status:
Active, not recruiting
Facility:
Name:
CHI Creteil
Address:
City:
Créteil
Country:
France
Status:
Recruiting
Contact:
Last name:
Lydia ROY, Dr
Investigator:
Last name:
Lydia ROY, Dr
Email:
Principal Investigator
Facility:
Name:
Ch La Rochelle
Address:
City:
La Rochelle
Country:
France
Status:
Recruiting
Contact:
Last name:
Emmanuel FLECK, Dr
Investigator:
Last name:
Emmanuel FLECK, Dr
Email:
Principal Investigator
Facility:
Name:
Chu Lille
Address:
City:
Lille
Country:
France
Status:
Recruiting
Contact:
Last name:
Valerie COITEUX, Dr
Investigator:
Last name:
Valérie COITEUX, Dr
Email:
Principal Investigator
Facility:
Name:
CHU Limoges
Address:
City:
Limoges
Country:
France
Status:
Recruiting
Contact:
Last name:
Amélie PENOT, Dr
Investigator:
Last name:
Amélie PENOT, Dr
Email:
Principal Investigator
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Franck NICOLINI, Dr
Investigator:
Last name:
Franck NICOLINI, Dr
Email:
Principal Investigator
Facility:
Name:
Ch Mont de Marsan
Address:
City:
Mont-de-Marsan
Country:
France
Status:
Recruiting
Contact:
Last name:
Samia MADENE HAROUNE, Dr
Investigator:
Last name:
Samia MADENE HAROUNE, Dr
Email:
Principal Investigator
Facility:
Name:
Chu Nancy
Address:
City:
Nancy
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Chu Nantes
Address:
City:
Nantes
Country:
France
Status:
Recruiting
Contact:
Last name:
Viviane DUBRUILLE, Dr
Investigator:
Last name:
Viviane DUBRUILLE, Dr
Email:
Principal Investigator
Facility:
Name:
Hopital Prive Du Confluent
Address:
City:
Nantes
Country:
France
Status:
Active, not recruiting
Facility:
Name:
Chu Poitiers
Address:
City:
Poitiers
Country:
France
Status:
Recruiting
Contact:
Last name:
José Miguel TORREGROSA DIAZ, Dr
Investigator:
Last name:
José Miguel TORREGROSA DIAZ, Dr
Email:
Principal Investigator
Facility:
Name:
Ch Perigueux
Address:
City:
Périgueux
Country:
France
Status:
Recruiting
Contact:
Last name:
Claire CALMETTE, Dr
Investigator:
Last name:
Claire CALMETTE, Dr
Email:
Principal Investigator
Facility:
Name:
Oncopole Toulouse
Address:
City:
Toulouse
Country:
France
Status:
Recruiting
Contact:
Last name:
Francoise HUGUET, Dr
Investigator:
Last name:
Francoise HUGUET, Dr
Email:
Principal Investigator
Facility:
Name:
Chu Tours
Address:
City:
Tours
Country:
France
Status:
Recruiting
Contact:
Last name:
Antoine MACHET, Dr
Investigator:
Last name:
Antoine MACHET, Dr
Email:
Principal Investigator
Facility:
Name:
CH Versailles
Address:
City:
Versailles
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe ROUSSELOT, Dr
Investigator:
Last name:
Philippe ROUSSELOT, Dr
Email:
Principal Investigator
Start date:
December 1, 2023
Completion date:
December 1, 2029
Lead sponsor:
Agency:
Poitiers University Hospital
Agency class:
Other
Source:
Poitiers University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05753384
