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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03573596
Recruitment Status : Recruiting
First Posted : June 29, 2018
Last Update Posted : June 29, 2018
Sponsor:
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
Information provided by (Responsible Party):
J.J.W.M. Janssen, 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.

Condition or disease Intervention/treatment Phase
CML, Relapsed Drug: Dasatinib Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Phase 2, multicenter study, prospective, open label, uncontrolled.
Masking: None (Open Label)
Primary Purpose: 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
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : February 1, 2024


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. successful MMR maintenance [ Time Frame: 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 :
  1. correlates with succesful stop [ Time Frame: 1 year ]
    Assessment of clinical and biological factors correlating with persistence of MMR or better after second TKI stop.

  2. reachievement of MR4 [ Time Frame: 1 year ]
    Number of patients who re-achieved stable MR4, and were offered study participation.

  3. Time to reachievement of MR4 [ Time Frame: 1 year ]
    Time to reachievement of MR4 after second loss of MMR.

  4. Adverse events after TKI withdrawal [ Time Frame: 1 year ]
    Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs.

  5. Overall survival [ Time Frame: 1 year ]
    Overall survival

  6. Progression-free survival [ Time Frame: 1 year ]
    Progression-free survival

  7. TKI restart without prior molecular relapse [ Time Frame: 1 year ]
    Occurrence of a restart of TKI without prior molecular relapse.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03573596


Contacts
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Contact: Ulla Olsson-Strömberg, MD PhD +46 (0) 18-611 00 00 ulla.stromberg@talk21.com
Contact: Jeroen JW Janssen, MD PhD +31204442230 jjwm.janssen@vumc.nl

Locations
Show Show 21 study locations
Sponsors and Collaborators
Amsterdam UMC, location VUmc
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
Investigators
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Principal Investigator: Ulla Olsson-Strömberg, MD PhD Department of Hematology, Uppsala University Hospital, Uppsala, Sweden
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Responsible Party: J.J.W.M. Janssen, Clinical Hematologist, Deputy Chief of Department of Hematology, Amsterdam UMC, location VUmc
ClinicalTrials.gov Identifier: NCT03573596    
Other Study ID Numbers: DASTOP2
First Posted: June 29, 2018    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Study results will be published as soon as possible. Steering committee will decide on sharing IPD. This is still pending.

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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
Keywords provided by J.J.W.M. Janssen, Amsterdam UMC, location VUmc:
CML
second stop
dasatinib
Additional relevant MeSH terms:
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action