Clinical Trials /

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

NCT03573596

Description:

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Persistence of MR3 in Chronic Myeloid Leukemia (CML) After a 2nd Stop of TKI 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

Clinical Trial IDs

  • ORG STUDY ID: DASTOP2
  • NCT ID: NCT03573596

Conditions

  • CML, Relapsed

Interventions

DrugSynonymsArms
Dasatinibdasatinib

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
dasatinibOther2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year
  • Dasatinib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:successful MMR maintenance
Time Frame:one year
Safety Issue:
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).

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:VU University Medical Center

Trial Keywords

  • CML
  • second stop
  • dasatinib

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