An observational study in Chronic Myeloid Leukemia, sponsored by University of Milano Bicocca. Completed at 26 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-29.
Sponsored by University of Milano Bicocca · Observational
The purpose of this study is to investigate the safety profile of TKI discontinuation in clinical practice, with particular regard on the risk of progression after treatment discontinuation.
This study will enroll approximately 3000 CP-CML patients that must have a history of at least 4 years of TKI treatment and at least 18 months of DMR. Events developing in patients after the end of discontinuation and TKI resumption will be considered as linked to the discontinuation if they will develop within 36 months from the end of discontinuation. This rule will apply also to subsequent TD attempts. In case of a second or subsequent discontinuation attempt after the failure of a previous one (for molecular relapse), patients must have re-achieved a DMR with TKI therapy resumption and must keep DMR for at least 18 months before another TD.
Collection of data will be retrospective and prospective, as each center will collect the data for 24 months. Patients who discontinued before the opening of this study will contribute to the retrospective cohort, while those who will discontinue after it will contribute to the prospective cohort. Patients who discontinued before the opening of this study but will continue their discontinuation after it, will contribute to both cohorts. For patients prospectively recruited, monitoring of disease status will be performed to assess the maintenance of the molecular remission during the study period.
Patients with an atypical BCR-ABL1 fusion gene, which does not allow the use of Q-RT-PCR, will be monitored by qualitative PCR and will be analyzed separately. For these patients, negativity of nested qualitative RT-PCR will be considered a surrogate of DMR of patients monitored by Q-RT-PCR, while loss of negativity of first-round qualitative PCR will be considered a surrogate of loss of MMR (i.e. molecular relapse). Accordingly, for patients monitored by qualitative PCR, TKI resumption after TD will be provided in case of a new positivity of first-round PCR.
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964 studies on the registry are indexed under Leukemia, Myelogenous, Chronic, BCR-ABL Positive; 109 are open to participants now.
This study's enrollment of 260 is above the median of 141 across 149 observational studies indexed under Leukemia, Myelogenous, Chronic, BCR-ABL Positive.
Browse Leukemia, Myelogenous, Chronic, BCR-ABL Positive studies →University of Milano Bicocca is the lead sponsor of 124 studies on the registry; 48 are open to participants now.
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The target population will include all CML patients presently eligible for treatment discontinuation independently of whether they discontinued or not. For the time they did not discontinue they will contribute to the reference cohort, while after TD they will contribute data to the discontinuation cohort. In case of treatment resumption, the patient will still contribute to the discontinuation cohort for 36 months after treatment resumption, while he/she will contribute to the reference cohort thereafter, assuming a new TD did not occur.
Exclusion Criteria:
Patients who discontinued before the opening of this study will contribute to the retrospective cohort.
Patients who will discontinue after it will contribute to the prospective cohort.
Patients who discontinued before the opening of this study but will continue their discontinuation after it, will contribute to both cohorts.
The quantification of the risk of progression
To quantify the risk of progression to accelerated phase (AP) or blast phase (BP), expressed as time adjusted rate (TAR), after TKI discontinuation in CML patients who undergo a first or subsequent TKI discontinuation attempt
Time frame: 36 Month
To compare the time adjusted rate (TAR) of progression from Chronic phase-Chronic Myeloid Leukemia to Accelerated phase (AP) or Blastic phase (BP) by using the percentage of blasts, promyelocytes, basophils or platelet in blood or bone marrow
To compare the TAR (time adjusted rate) of progression to AP or BP that is obtained in the target population to that obtained in a similar population of patients with the same characteristics who do not discontinue TKI treatment
Time frame: 36 Month
Progression free survival (PFS) after TKI discontinuation.
PFS will be defined as time between discontinuation and progression to AP or BP.
Time frame: 36 Month
Rate of molecular relapse (loss of MR3 or MMR)
Rate of molecular relapse (loss of MR3 or MMR) at 12 and 24 months after TKI discontinuation.
Time frame: 36 Month
Relapse free survival (RFS) after TKI discontinuation.
Relapse free survival (RFS) after TKI discontinuation. RFS will be defined as time between discontinuation and loss of MMR (i.e. molecular relapse).
Time frame: 36 Month
Percentage of relapsed patients who obtain a new deep molecular response (DMR) within 6-12 months of treatment resumption among all patients who restart TKI treatment because of a molecular relapse after TKI discontinuation.
The following criteria will be used to define DMR (43): * MR4 = either (i) detectable disease with \<0.01% BCR-ABL1IS or (ii) undetectable disease in cDNA with \>10 000 ABL1 transcripts. * MR4.5 = either (i) detectable disease with \<0.0032% BCR-ABL1IS or (ii) undetectable disease in cDNA with \>32 000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1. * MR5 = either (i) detectable disease with \<0.001% BCR-ABL1IS or (ii) undetectable disease in cDNA with \>100 000 ABL1 transcripts in the same volume of cDNA used to test for BCR-ABL1.
Time frame: 36 Month
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive→
University of Milano Bicocca