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

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.

Study Overview

• Status: Recruiting
• Conditions: CML, Relapsed
• Intervention / Treatment: Drug: Dasatinib

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 Type: Interventional
• Enrollment (Anticipated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ulla Olsson-Strömberg, MD PhD; Phone Number: +46 (0) 18-611 00 00; Email: ulla.stromberg@talk21.com
• Study Contact Backup: Name: Jeroen JW Janssen, MD PhD; Phone Number: +31204442230; Email: jjwm.janssen@vumc.nl

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: dasatinib; 2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year	Drug: Dasatinib; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	1 year
correlates with succesful stop	Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop.	1 year
reachievement of MR4	Number of patients who re-achieved stable MR4, and were offered study participation.	1 year
Time to reachievement of MR4	Time to reachievement of MR4 after second loss of MMR.	1 year
Adverse events after TKI withdrawal	Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs.	1 year
Progression-free survival	Progression-free survival	1 year
TKI restart without prior molecular relapse	Occurrence of a restart of TKI without prior molecular relapse.	1 year

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Odense University Hospital; Helsinki University Central Hospital; Aarhus University Hospital; Helse Stavanger HF; St. Olavs Hospital; University Hospital, Bonn; Skane University Hospital; Henri Mondor University Hospital; Uppsala University Hospital
• Investigators: Principal Investigator: Ulla Olsson-Strömberg, MD PhD, Department of Hematology, Uppsala University Hospital, Uppsala, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 29, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: CML; dasatinib; second stop
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: DASTOP2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Study results will be published as soon as possible. Steering committee will decide on sharing IPD. This is still pending.

Drug and device information, study documents

• 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