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

Phase 2

• Conditions: CML, Relapsed
• Interventions: Drug: Dasatinib

• Registration Number: NCT03573596
• Lead Sponsor: Amsterdam UMC, location VUmc

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).

Study Timeline

• Study Start: 2018-02-01
• Study First Submitted: 2018-05-22
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-19
• Last Update Submitted: 2018-06-19
• Study First Posted: 2018-06-29
• Last Update Posted: 2018-06-29
• Primary Completion: 2023-02-01
• Study Completion: 2024-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 134

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
dasatinib	Dasatinib	2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
correlates with succesful stop	1 year	Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop.
reachievement of MR4	1 year	Number of patients who re-achieved stable MR4, and were offered study participation.
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.
Overall survival	1 year	Overall survival
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.

Trial Locations

Locations (20)

Helsinki University Hospital; 🇫🇮 Helsinki, Finland

VU University medical center; 🇳🇱 Amsterdam, Netherlands

Radboud University medical center; 🇳🇱 Nijmegen, Netherlands

Albert Schweitzer Hospital; 🇳🇱 Dordrecht, Netherlands

Tromsø University Hospital; 🇳🇴 Tromsø, Norway

Odense University Hospital; 🇩🇰 Odense, Denmark

Sunderby Sjukhus; 🇸🇪 Luleå, Sweden

Lund University Hospital; 🇸🇪 Lund, Sweden

Karolinska Hospital; 🇸🇪 Stockholm, Sweden

Uppsala University Hospital (Akademiska); 🇸🇪 Uppsala, Sweden

University Hospital; 🇸🇪 Linköping, Sweden

Erasmus University medical center; 🇳🇱 Rotterdam, Netherlands

Oslo University Hospital; 🇳🇴 Oslo, Norway

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

Umeå University Hospital; 🇸🇪 Umeå, Sweden

Örebro University Hospital; 🇸🇪 Örebro, Sweden

Centre Hospitalo-Universitaire; 🇫🇷 Créteil, France

Haukeland, Bergen University Hospital; 🇳🇴 Bergen, Norway

St Olavs Hospital-Trondheim University Hospital; 🇳🇴 Trondheim, Norway

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark