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

NCT03573596 | Unknown Phase 2

• 1 other identifier: DASTOP2
• Study Type: interventional
• Target: 134
• Locations: 7 countries
• Sites: 21

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.

Conditions

CML, Relapsed

Keywords

CML; second stop; dasatinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• correlates with succesful stop

  1 year

• reachievement of MR4

  1 year

• Time to reachievement of MR4

  1 year

• Adverse events after TKI withdrawal

  1 year

• Overall survival

  1 year

Study Arms (1)

dasatinib

OTHER

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

Drug: Dasatinib

Interventions

Dasatinib DRUG

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.

dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Treated with TKI for at least one year after having failed a prior attempt to stop TKI. Previous TKI can be any.
• Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course.
• years or older.

You may not qualify if:

• Previous hematological relapse after first stop of TKI.
• Previous AP/BC at any time in the history of the disease.
• Restart of TKI without loss of MMR after first stop
• Current participation in another clinical study.
• Previous or planned allogeneic stem cell transplantation.
• Patients with contra-indications to dasatinib therapy due to comorbidities.
• Subjects with acute hepatitis B virus (HBV) infections.
• Uncontrolled or significant cardiovascular disease.
• Pulmonary arterial hypertension.
• Pleural or pericardial effusions of any grade at study entry are excluded
• History of significant bleeding disorder unrelated to CML
• Hypersensitivity to dasatinib and excipients of dasatinib tablets.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Uppsala University Hospital: collaborator
• Skane University Hospital: collaborator
• Helsinki University Central Hospital: collaborator
• Odense University Hospital: collaborator
• Henri Mondor University Hospital: collaborator
• St. Olavs Hospital: collaborator
• Helse Stavanger HF: collaborator
• Aarhus University Hospital: collaborator
• University Hospital, Bonn: collaborator

Study Sites (21)

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Helsinki University Hospital

Helsinki, Finland

RECRUITING

Centre Hospitalo-Universitaire

Créteil, France

NOT YET RECRUITING

University Hospital

Bonn, Germany

RECRUITING

VU University medical center

Amsterdam, 1081HV, Netherlands

NOT YET RECRUITING

Albert Schweitzer Hospital

Dordrecht, Netherlands

NOT YET RECRUITING

Radboud University medical center

Nijmegen, Netherlands

NOT YET RECRUITING

Erasmus University medical center

Rotterdam, Netherlands

NOT YET RECRUITING

Haukeland, Bergen University Hospital

Bergen, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Stavanger University Hospital

Stavanger, Norway

RECRUITING

Tromsø University Hospital

Tromsø, Norway

RECRUITING

St Olavs Hospital-Trondheim University Hospital

Trondheim, Norway

RECRUITING

University Hospital

Linköping, Sweden

RECRUITING

Sunderby Sjukhus

Luleå, Sweden

RECRUITING

Lund University Hospital

Lund, Sweden

RECRUITING

Örebro University Hospital

Örebro, Sweden

RECRUITING

Karolinska Hospital

Stockholm, Sweden

RECRUITING

Umeå University Hospital

Umeå, Sweden

RECRUITING

Uppsala University Hospital (Akademiska)

Uppsala, Sweden

RECRUITING

Related Publications (1)

• Flygt H, Soderlund S, Richter J, Saussele S, Koskenvesa P, Stenke L, Mustjoki S, Dimitrijevic A, Stentoft J, Majeed W, Roy L, Wolf D, Dreimane A, Gjertsen BT, Gedde-Dahl T, Ahlstrand E, Markevarn B, Hjorth-Hansen H, Janssen J, Olsson-Stromberg U. Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial. Leukemia. 2024 Apr;38(4):781-787. doi: 10.1038/s41375-024-02145-6. Epub 2024 Jan 26.

  PMID: 38278960 DERIVED

MeSH Terms

Conditions

Recurrence

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Ulla Olsson-Strömberg, MD PhD

  Department of Hematology, Uppsala University Hospital, Uppsala, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ulla Olsson-Strömberg, MD PhD

CONTACT

+46 (0) 18-611 00 00; ulla.stromberg@talk21.com

Jeroen JW Janssen, MD PhD

CONTACT

+31204442230; jjwm.janssen@vumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Hematologist, Deputy Chief of Department of Hematology

Model Details: Phase 2, multicenter study, prospective, open label, uncontrolled.

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 29, 2018
• Study Start: February 1, 2018
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2024
• Last Updated: June 29, 2018

Record last verified: 2018-06

Locations

SE (7); DE (1); DK (2); FI (1); NL (4); NO (5); FR (1)