CML, Relapsed Clinical Trial
— DASTOP2Official 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
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.
| Status | Recruiting |
| Enrollment | 134 |
| Est. completion date | February 1, 2024 |
| Est. primary completion date | February 1, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Denmark | Aarhus University Hospital | Aarhus | |
| Denmark | Odense University Hospital | Odense | |
| Finland | Helsinki University Hospital | Helsinki | |
| France | Centre Hospitalo-Universitaire | Créteil | |
| Germany | University Hospital | Bonn | |
| Netherlands | VU University medical center | Amsterdam | |
| Netherlands | Albert Schweitzer Hospital | Dordrecht | |
| Netherlands | Radboud University medical center | Nijmegen | |
| Netherlands | Erasmus University medical center | Rotterdam | |
| Norway | Haukeland, Bergen University Hospital | Bergen | |
| Norway | Oslo University Hospital | Oslo | |
| Norway | Stavanger University Hospital | Stavanger | |
| Norway | Tromsø University Hospital | Tromsø | |
| Norway | St Olavs Hospital-Trondheim University Hospital | Trondheim | |
| Sweden | University Hospital | Linköping | |
| Sweden | Sunderby Sjukhus | Luleå | |
| Sweden | Lund University Hospital | Lund | |
| Sweden | Örebro University Hospital | Örebro | |
| Sweden | Karolinska Hospital | Stockholm | |
| Sweden | Umeå University Hospital | Umeå | |
| Sweden | Uppsala University Hospital (Akademiska) | Uppsala |
| Lead Sponsor | Collaborator |
|---|---|
| VU University Medical Center | Aarhus University Hospital, Helse Stavanger HF, Helsinki University Central Hospital, Henri Mondor University Hospital, Odense University Hospital, Skane University Hospital, St. Olavs Hospital, University Hospital, Bonn, Uppsala University Hospital |
Denmark, Finland, France, Germany, Netherlands, Norway, Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | correlates with succesful stop | Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop. | 1 year | |
| Secondary | reachievement of MR4 | Number of patients who re-achieved stable MR4, and were offered study participation. | 1 year | |
| Secondary | Time to reachievement of MR4 | Time to reachievement of MR4 after second loss of MMR. | 1 year | |
| Secondary | Adverse events after TKI withdrawal | Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs. | 1 year | |
| Secondary | Overall survival | Overall survival | 1 year | |
| Secondary | Progression-free survival | Progression-free survival | 1 year | |
| Secondary | TKI restart without prior molecular relapse | Occurrence of a restart of TKI without prior molecular relapse. | 1 year |