Persistence of MR3 in Chronic Myeloid Leukemia (CML) After a 2nd Stop of TKI Treatment

Study Overview
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Brief Summary
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This study will enroll CML patients who have failed a first TKI stopping attempt. After failure and at least a year of TKI treatment, patients will proceed to dasatinib treatment for another 2 years. If MR4 or better is re-achieved and maintained for at least one year, patients will be eligible for a second stop. After verification of MR4, TKI treatment will be stopped and patients followed in the same manner as after first stop. If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted.

Detailed Description
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The DASTOP2 study aims to retreat patients who relapse in the Euro-SKI study (or who stopped TKI treatment outside trials but according to EURO-SKI procedures), with TKI for at least another 3 years, out of last two years with dasatinib. If MR4 or better is re-achieved and maintained for at least one year, patients will be eligible for a second stop. After verification of MR4, TKI treatment will be stopped and patients followed in the same manner as after first stop. If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted. Patients exhibiting hematological relapse after first stop attempt will not be offered a second stop within this study. The same applies to patients in whom TKI was restarted prematurely (without loss of MMR).

Official Title
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Persistence Of Major Molecular Remission In Chronic Myeloid Leukemia After A Second Stop Of Tki Treatment In Patients Who Failed An Initial Stop Attempt: A Multicenter Prospective Trial

Conditions
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CML, Relapsed

Intervention / Treatment
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* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CML in chronical phase (CP) under TKI treatment after failing a prior attempt to stop treatment within EURO-SKI or outside the study but according to EURO-SKI trial procedures. For the latter group this requires at least 3 years of TKI treatment (first line or second line due to intolerance to first line) before first stop, and MR4 for at least one year before stopping. Treated with TKI for at least one year after having failed a prior attempt to stop TKI. Previous TKI can be any. Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course. 18 years or older. Exclusion Criteria: Previous hematological relapse after first stop of TKI. Previous AP/BC at any time in the history of the disease. Restart of TKI without loss of MMR after first stop Current participation in another clinical study. Previous or planned allogeneic stem cell transplantation. Patients with contra-indications to dasatinib therapy due to comorbidities. Subjects with acute hepatitis B virus (HBV) infections. Uncontrolled or significant cardiovascular disease. Pulmonary arterial hypertension. Pleural or pericardial effusions of any grade at study entry are excluded History of significant bleeding disorder unrelated to CML Hypersensitivity to dasatinib and excipients of dasatinib tablets.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 2, multicenter study, prospective, open label, uncontrolled.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: dasatinib<br>2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year | Drug: Dasatinib<br>* CML patients who have failed a first stopping attempt and have used any TKI for one year will switch to dasatinib 100 mg qd for an additional 2 years before second stop attempt.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| successful MMR maintenance | The proportion of patients maintaining MMR at 12 months after discontinuing TKI a second time (survival without loss of major molecular response, MMR, defined as BCR-ABL1 > 0.1% on IS at one time point). | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| correlates with succesful stop | Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop. | 1 year | 
| reachievement of MR4 | Number of patients who re-achieved stable MR4, and were offered study participation. | 1 year | 
| Time to reachievement of MR4 | Time to reachievement of MR4 after second loss of MMR. | 1 year | 
| Adverse events after TKI withdrawal | Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs. | 1 year | 
| Overall survival | Overall survival | 1 year | 
| Progression-free survival | Progression-free survival | 1 year | 
| TKI restart without prior molecular relapse | Occurrence of a restart of TKI without prior molecular relapse. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML, second stop, dasatinib