Clinical Trials /

De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia

NCT01804985

Description:

The purpose of this study is to investigate whether some patients with excellent responses to chronic myeloid leukaemia (CML) treatment are being overtreated, and can remain well on either a lower dose of treatment or without treatment at all. The dose of imatinib (Glivec), nilotinib (Tasigna) or dasatinib (Sprycel) treatment will initially be cut to half the standard dose for 12 months, and then treatment will be stopped completely for a further two years. The trial information will also help to develop a de-escalation and stopping strategy for future newly diagnosed CML patients in the next British national CML study (to be known as SPIRIT3).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia
  • Official Title: A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy

Clinical Trial IDs

  • ORG STUDY ID: 4203
  • NCT ID: NCT01804985

Conditions

  • Chronic Myeloid Leukaemia

Interventions

DrugSynonymsArms
ImatinibGlivec or GleevecDe-escalated Treatment
nilotinibTasignaDe-escalated Treatment
dasatinibSprycelDe-escalated Treatment

Purpose

The purpose of this study is to investigate whether some patients with excellent responses to chronic myeloid leukaemia (CML) treatment are being overtreated, and can remain well on either a lower dose of treatment or without treatment at all. The dose of imatinib (Glivec), nilotinib (Tasigna) or dasatinib (Sprycel) treatment will initially be cut to half the standard dose for 12 months, and then treatment will be stopped completely for a further two years. The trial information will also help to develop a de-escalation and stopping strategy for future newly diagnosed CML patients in the next British national CML study (to be known as SPIRIT3).

Detailed Description

      The next definitive UK phase III trial in chronic myeloid leukaemia (CML) will be SPIRIT3,
      which will open shortly. This will incorporate a de-escalation and stopping strategy for
      patients who achieve excellent responses after at least 3 years of treatment with a tyrosine
      kinase inhibitor (TKI).

      DESTINY is to act as a pilot for this strategy in SPIRIT3, by defining the proportion of
      patients that relapse during 12 months of TKI de-escalation followed by 24 months of
      cessation. DESTINY also includes scientific bolt-on studies, quality of life assessments and
      health economic evaluation.
    

Trial Arms

NameTypeDescriptionInterventions
De-escalated TreatmentExperimentalImatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months
  • Imatinib
  • nilotinib
  • dasatinib

Eligibility Criteria

        Inclusion Criteria:

          1. CML in first chronic phase.

          2. Demonstration of BCR-ABL1 positivity at/shortly after original diagnosis.

          3. Written Informed Consent

          4. Must have received TKI treatment for at least 3 years.

          5. At least 3 molecular results over the preceding 12 months, that fit either of the
             following groups (results from any UK lab are acceptable):

               -  (MR4 group) all the available BCR-ABL1 molecular results over the preceding 12
                  months are in MR4 (MR4 is defined as a BCR-ABL1/ABL1 ratio of zero, (reported to
                  International Standards (IS) where possible; with at least 10,000 ABL1 control
                  transcripts).

               -  (MMR group) some or all BCR-ABL1 molecular results are in major molecular
                  response (MMR), defined here as a BCR-ABL1/ABL1 ratio of 0.1% or less, (reported
                  to International Standard (IS) where possible), but not zero, with at least
                  10,000 ABL1 control transcripts. If the results over the preceding 12 months are
                  a mix of MMR and undetectable BCR-ABL1, then the patient is eligible for the MMR
                  but not the MR4 group.

        Exclusion Criteria:

          1. Age under 18

          2. Life expectancy predicted to be less than 37 months because of intercurrent illness

          3. Presence of serious concomitant illness (e.g. heart, renal, respiratory or active
             malignant disease) that might preclude completion of the trial

          4. CML in accelerated phase or blast crisis at any time

          5. Any molecular result during the preceding 12 months that is not in either MMR or MR4.

          6. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
             dasatinib) twice or more because of intolerance

          7. Treatment with higher than standard TKI doses ('standard' is defined as imatinib 400mg
             daily, nilotinib 400mg twice daily or dasatinib 100mg daily). However, an exception is
             made for patients who at original diagnosis commenced on either 800mg of imatinib on
             the SPIRIT1 study, or 140mg (or 70mg b.d) of dasatinib in the Bristol-Myers Squibb 034
             study. In each case these latter patients ARE eligible provided they fulfil other
             molecular criteria, since they do not demonstrate resistant disease.

          8. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
             dasatinib) because of resistance. Patients treated with lower (but at least 50%) than
             the standard TKI doses (as defined in previous criterion) for tolerance reasons may be
             included, but will de-escalate to the same doses as for standard dose patients and
             will be analysed separately, as they could be seen as undertreated.

          9. Previous treatment with ponatinib or bosutinib. Patients who received interferon prior
             to commencing TKI (even if resistant to their interferon) are eligible, provided their
             response to TKI fits the entry criteria.

         10. Pregnant or lactating women

         11. Women of childbearing potential (including women whose last menstrual period was less
             than one year prior to screening) who are unable or unwilling to use adequate
             contraception from study start to one year after the last dose of protocol therapy.
             Adequate contraception is defined as hormonal birth control, intrauterine device,
             double barrier method or total abstinence.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:• The proportion of patients who can first de-escalate their treatment (to half the standard dose of their TKI) for 12 months, and then stop treatment completely for a further 2 years, without losing MMR.
Time Frame:37months
Safety Issue:
Description:• The proportion of patients who can first de-escalate their treatment (to half the standard dose of their TKI) for 12 months, and then stop treatment completely for a further 2 years, without losing MMR.

Secondary Outcome Measures

Measure:• Proportion of patients who can successfully de-escalate their treatment (to half the standard dose of their TKI), but who then lose MMR on complete TKI cessation
Time Frame:37 months
Safety Issue:
Description:• Proportion of patients who can successfully de-escalate their treatment (to half the standard dose of their TKI), but who then lose MMR on complete TKI cessation
Measure:• Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI
Time Frame:37 months
Safety Issue:
Description:• Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI
Measure:• Quality of Life
Time Frame:37 months
Safety Issue:
Description:• Quality of Life
Measure:• Health Economic Assessment
Time Frame:37 months
Safety Issue:
Description:• Health Economic Assessment
Measure:• Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation.
Time Frame:37 months
Safety Issue:
Description:• Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:University of Liverpool

Last Updated

May 4, 2017