CML, Relapsed
Conditions
Keywords
CML, second stop, dasatinib
Brief summary
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).
Interventions
DRUGDasatinib
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.
Sponsors
Uppsala University Hospital
Skane University Hospital
Helsinki University Central Hospital
Odense University Hospital
Henri Mondor University Hospital
St. Olavs Hospital
Helse Stavanger HF
Aarhus University Hospital
University Hospital, Bonn
Amsterdam UMC, location VUmc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 2, multicenter study, prospective, open label, uncontrolled.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| successful MMR maintenance | one year | 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
| Measure | Time frame | Description |
|---|---|---|
| correlates with succesful stop | 1 year | Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop. |
| Time to reachievement of MR4 | 1 year | Time to reachievement of MR4 after second loss of MMR. |
| Adverse events after TKI withdrawal | 1 year | Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs. |
| reachievement of MR4 | 1 year | Number of patients who re-achieved stable MR4, and were offered study participation. |
| Progression-free survival | 1 year | Progression-free survival |
| TKI restart without prior molecular relapse | 1 year | Occurrence of a restart of TKI without prior molecular relapse. |
| Overall survival | 1 year | Overall survival |
Countries
Denmark, Finland, France, Germany, Netherlands, Norway, Sweden
Contacts
Primary ContactUlla Olsson-Strömberg, MD PhD
Backup ContactJeroen JW Janssen, MD PhD
Outcome results
None listed