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Persistence of MR3 in Chronic Myeloid Leukemia (CML) After a 2nd Stop of TKI Treatment (DASTOP2)

Primary Purpose

CML, Relapsed

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CML, Relapsed focused on measuring CML, second stop, dasatinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Aarhus University HospitalRecruiting
  • Odense University HospitalRecruiting
  • Helsinki University HospitalRecruiting
  • Centre Hospitalo-Universitaire
  • University HospitalRecruiting
  • VU University medical center
  • Albert Schweitzer Hospital
  • Radboud University medical center
  • Erasmus University medical center
  • Haukeland, Bergen University HospitalRecruiting
  • Oslo University HospitalRecruiting
  • Stavanger University HospitalRecruiting
  • Tromsø University HospitalRecruiting
  • St Olavs Hospital-Trondheim University HospitalRecruiting
  • University HospitalRecruiting
  • Sunderby SjukhusRecruiting
  • Lund University HospitalRecruiting
  • Karolinska HospitalRecruiting
  • Umeå University HospitalRecruiting
  • Uppsala University Hospital (Akademiska)Recruiting
  • Örebro University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

dasatinib

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

correlates with succesful stop
Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop.
reachievement of MR4
Number of patients who re-achieved stable MR4, and were offered study participation.
Time to reachievement of MR4
Time to reachievement of MR4 after second loss of MMR.
Adverse events after TKI withdrawal
Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs.
Overall survival
Overall survival
Progression-free survival
Progression-free survival
TKI restart without prior molecular relapse
Occurrence of a restart of TKI without prior molecular relapse.

Full Information

First Posted
May 22, 2018
Last Updated
June 19, 2018
Sponsor
Amsterdam UMC, location VUmc
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT03573596
Brief Title
Persistence of MR3 in Chronic Myeloid Leukemia (CML) After a 2nd Stop of TKI Treatment
Acronym
DASTOP2
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

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2018 (Actual)
Primary Completion Date
February 1, 2023 (Anticipated)
Study Completion Date
February 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CML, Relapsed
Keywords
CML, second stop, dasatinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 2, multicenter study, prospective, open label, uncontrolled.
Masking
None (Open Label)
Allocation
N/A
Enrollment
134 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
dasatinib
Arm Type
Other
Arm Description
2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Intervention Description
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.
Primary Outcome Measure Information:
Title
successful MMR maintenance
Description
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).
Time Frame
one year
Secondary Outcome Measure Information:
Title
correlates with succesful stop
Description
Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop.
Time Frame
1 year
Title
reachievement of MR4
Description
Number of patients who re-achieved stable MR4, and were offered study participation.
Time Frame
1 year
Title
Time to reachievement of MR4
Description
Time to reachievement of MR4 after second loss of MMR.
Time Frame
1 year
Title
Adverse events after TKI withdrawal
Description
Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs.
Time Frame
1 year
Title
Overall survival
Description
Overall survival
Time Frame
1 year
Title
Progression-free survival
Description
Progression-free survival
Time Frame
1 year
Title
TKI restart without prior molecular relapse
Description
Occurrence of a restart of TKI without prior molecular relapse.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 18 years or older. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ulla Olsson-Strömberg, MD PhD
Phone
+46 (0) 18-611 00 00
Email
ulla.stromberg@talk21.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jeroen JW Janssen, MD PhD
Phone
+31204442230
Email
jjwm.janssen@vumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulla Olsson-Strömberg, MD PhD
Organizational Affiliation
Department of Hematology, Uppsala University Hospital, Uppsala, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesper Stentoft, MD PhD
Phone
+45 78 45 00 00
Email
jespsten@rm.dk
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreja Dimitrijevic, MD PhD
Phone
+45 66 11 33 33
Email
Andreja.Dimitrijevic@rsyd.dk
Facility Name
Helsinki University Hospital
City
Helsinki
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Satu Mustjoki, MD PhD
Phone
+358-9-47171898
First Name & Middle Initial & Last Name & Degree
Perttu Koskenvesa, MD PhD
Email
perttu.koskenvesa@helsinki.fi
Facility Name
Centre Hospitalo-Universitaire
City
Créteil
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lydia Roy, MD PhD
Phone
+33 1 49 81 21 11
Email
lydia.roy@aphp.fr
Facility Name
University Hospital
City
Bonn
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominik Wolf, MD PhD
Phone
+49 228 2870
Email
dominik.wolf@ukbonn.de
Facility Name
VU University medical center
City
Amsterdam
ZIP/Postal Code
1081HV
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeroen JW Janssen, MD PhD
Phone
+31204442230
Email
jjwm.janssen@vumc.nl
First Name & Middle Initial & Last Name & Degree
Gert J Ossenkoppele, MD PhD
Phone
+31204442230
Email
g.ossenkoppele@vumc.nl
Facility Name
Albert Schweitzer Hospital
City
Dordrecht
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter E Westerweel, MD PhD
Phone
+3178654 11 11
Email
p.e.westerweel@asz.nl
Facility Name
Radboud University medical center
City
Nijmegen
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole Blijlevens, MD PhD
Phone
+3124366 82 06
Email
Nicole.Blijlevens@radboudumc.nl
Facility Name
Erasmus University medical center
City
Rotterdam
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter AW te Boekhorst, MD PhD
Phone
+3110 703 49 11
Email
p.teboekhorst@erasmusmc.nl
Facility Name
Haukeland, Bergen University Hospital
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bjørn Tore Gjertsen, MD PhD
Phone
+47 55 97 50 00
Email
bjorn.gjertsen@uib.no
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Gedde Dahl, MD PhD
Phone
+47 915 02770
Email
tobias.gedde-dahl@rikshospitalet.no
Facility Name
Stavanger University Hospital
City
Stavanger
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Waleed Majeed, MD PhD
Phone
+47 51 51 80 00
Email
waleed.majeed.mohammed@sus.no
Facility Name
Tromsø University Hospital
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anders Vik, MD PhD
Phone
+47 77 62 60 00
Email
anders.vik@uit.no
Facility Name
St Olavs Hospital-Trondheim University Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik Hjorth Hansen, MD PhD
Phone
+47 72 57 30 00
Email
henrik.hjorth-hansen@ntnu.no
Facility Name
University Hospital
City
Linköping
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kourosh Lofti, MD PhD
Phone
+46 10 103 00 00
Email
Kourosh.Lotfi@regionostergotland.se
First Name & Middle Initial & Last Name & Degree
Arta Dreimane, MDPhD
Email
Arta.Dreimane@regionostergotland.se
Facility Name
Sunderby Sjukhus
City
Luleå
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anneli Enblom-Larsson, MD PhD
Phone
+46 920 28 20 00
Email
anneli.enblom-larsson@nll.se
Facility Name
Lund University Hospital
City
Lund
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan Richter, MD PhD
Phone
+46 46 17 10 00
Email
johan.richter@med.lu.se
Facility Name
Karolinska Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leif Stenke, MD PhD
Phone
+46 8 517 700 00
Email
leif.stenke@ki.se
First Name & Middle Initial & Last Name & Degree
Lotta Ohm, MD PhD
Email
lotta.ohm@swipnet.se
Facility Name
Umeå University Hospital
City
Umeå
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Berit Markevärn, MD PhD
Phone
+46 90 785 00 00
Email
berit.markevarn@vll.se
Facility Name
Uppsala University Hospital (Akademiska)
City
Uppsala
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulla Olsson-Strömberg, MD PhD
Phone
+46 (0) 18-611 00 00
Email
ulla.stromberg@talk21.com
First Name & Middle Initial & Last Name & Degree
Stina Söderlund, MD PhD
Email
stina.soderlund@akademiska.se
Facility Name
Örebro University Hospital
City
Örebro
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mats Björeman, MD PhD
Phone
+46 19 602 10 00
Email
mats.bjoreman@regionorebrolan.se

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Study results will be published as soon as possible. Steering committee will decide on sharing IPD. This is still pending.

Learn more about this trial

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

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