Clinical trial NCT03573596: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: CML, Relapsed
Keywords: CML
second stop
dasatinib
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
name: Skane University Hospital
name: Helsinki University Central Hospital
name: Odense University Hospital
name: Henri Mondor University Hospital
name: St. Olavs Hospital
name: Helse Stavanger HF
name: Aarhus University Hospital
name: University Hospital, Bonn
First posted: 2018-06-29
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 2, multicenter study, prospective, open label, uncontrolled.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: successful MMR maintenance
timeFrame: one year
Secondary outcomes:
measure: correlates with succesful stop
timeFrame: 1 year
measure: reachievement of MR4
timeFrame: 1 year
measure: Time to reachievement of MR4
timeFrame: 1 year
measure: Adverse events after TKI withdrawal
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Progression-free survival
timeFrame: 1 year
measure: TKI restart without prior molecular relapse
timeFrame: 1 year
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Créteil
country: France
facility: Centre Hospitalo-Universitaire
city: Bonn
country: Germany
facility: University Hospital
city: Amsterdam
country: Netherlands
facility: VU University medical center
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Nijmegen
country: Netherlands
facility: Radboud University medical center
city: Rotterdam
country: Netherlands
facility: Erasmus University medical center
city: Bergen
country: Norway
facility: Haukeland, Bergen University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: Tromsø University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital-Trondheim University Hospital
city: Linköping
country: Sweden
facility: University Hospital
city: Luleå
country: Sweden
facility: Sunderby Sjukhus
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital (Akademiska)
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Department of Hematology, Uppsala University Hospital, Uppsala, Sweden
name: Ulla Olsson-Strömberg, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: