Description:
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.
Title
- Brief Title: Persistence of MR3 in Chronic Myeloid Leukemia (CML) After a 2nd Stop of TKI Treatment
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
DASTOP2
- NCT ID:
NCT03573596
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Dasatinib | | dasatinib |
Purpose
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
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).
Trial Arms
Name | Type | Description | Interventions |
---|
dasatinib | Other | 2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year | |
Eligibility Criteria
Inclusion Criteria:
1. 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.
2. Treated with TKI for at least one year after having failed a prior attempt to stop
TKI. Previous TKI can be any.
3. Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis
or later during the disease course.
4. 18 years or older.
Exclusion Criteria:
1. Previous hematological relapse after first stop of TKI.
2. Previous AP/BC at any time in the history of the disease.
3. Restart of TKI without loss of MMR after first stop
4. Current participation in another clinical study.
5. Previous or planned allogeneic stem cell transplantation.
6. Patients with contra-indications to dasatinib therapy due to comorbidities.
7. Subjects with acute hepatitis B virus (HBV) infections.
8. Uncontrolled or significant cardiovascular disease.
9. Pulmonary arterial hypertension.
10. Pleural or pericardial effusions of any grade at study entry are excluded
11. History of significant bleeding disorder unrelated to CML
12. Hypersensitivity to dasatinib and excipients of dasatinib tablets.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | successful MMR maintenance |
Time Frame: | one year |
Safety Issue: | |
Description: | 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). |
Secondary Outcome Measures
Measure: | correlates with succesful stop |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop. |
Measure: | reachievement of MR4 |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Number of patients who re-achieved stable MR4, and were offered study participation. |
Measure: | Time to reachievement of MR4 |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Time to reachievement of MR4 after second loss of MMR. |
Measure: | Adverse events after TKI withdrawal |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs. |
Measure: | Overall survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Overall survival |
Measure: | Progression-free survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Progression-free survival |
Measure: | TKI restart without prior molecular relapse |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Occurrence of a restart of TKI without prior molecular relapse. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | VU University Medical Center |
Trial Keywords
Last Updated
June 29, 2018