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CompletedNCT01804985DESTINYUpdated Mar 14, 2025

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

A Phase 2 interventional study of Imatinib and nilotinib in Chronic Myeloid Leukaemia, sponsored by University of Liverpool. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-14.

Sponsored by University of Liverpool · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
174
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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).

Read the detailed description

The next definitive United Kingdom (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.

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Conditions studied

  • Chronic Myeloid Leukaemia
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 637 are open to participants now.

This study's enrollment of 174 is above the median of 38 across 4,248 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

University of Liverpool is the lead sponsor of 99 studies on the registry; 10 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
174 participants (actual)

Study arms

  • Experimental
    De-escalated Treatment

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

    Drug: Imatinib · Drug: nilotinib · Drug: dasatinib

Interventions

  • DrugImatinib

    Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. If on imatinib, the dose should be decreased to 200mg daily;

    Also known as: Glivec or Gleevec

  • Drugnilotinib

    Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. if on nilotinib to 200mg twice daily (which is half the standard dose for second line use, since it is anticipated that the vast majority of nilotinib entrants will be receiving 400mg twice daily because of prior imatinib intolerance);

    Also known as: Tasigna

  • Drugdasatinib

    Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months. If on dasatinib then to 50 mg daily.

    Also known as: Sprycel

06

What researchers measure

Primary outcomes

  1. • 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.

    • 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

Secondary outcomes

  1. • 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

    • 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

  2. • Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI

    • Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI

    Time frame: 37 months

  3. • Quality of Life

    • Quality of Life

    Time frame: 37 months

  4. • Health Economic Assessment

    • Health Economic Assessment

    Time frame: 37 months

  5. • Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation.

    • Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation.

    Time frame: 37 months

07

Study locations

1 site
  • University of Liveprool
    Liverpool, L69 3GL, United Kingdom
08

References and documents

Publications

  • Clark RE, Polydoros F, Apperley JF, Milojkovic D, Rothwell K, Pocock C, Byrne J, de Lavallade H, Osborne W, Robinson L, O'Brien SG, Read L, Foroni L, Copland M. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematol. 2019 Jul;6(7):e375-e383. doi: 10.1016/S2352-3026(19)30094-8. Epub 2019 Jun 12. PubMed 31201085 ↗
  • Clark RE, Polydoros F, Apperley JF, Milojkovic D, Pocock C, Smith G, Byrne JL, de Lavallade H, O'Brien SG, Coffey T, Foroni L, Copland M. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 2017 Jul;4(7):e310-e316. doi: 10.1016/S2352-3026(17)30066-2. Epub 2017 May 26. PubMed 28566209 ↗

Related links

Study documents

  • Study protocol · May 24, 2018
  • Statistical analysis plan · Jul 17, 2019

Documents are hosted by the registry — open the source record to download them.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 14, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01804985
Lead sponsor
University of Liverpool
Collaborators
Newcastle University, Imperial College London, University of Glasgow
Responsible party
Sponsor
First posted
Mar 5, 2013
Start date
Dec 2013
Primary completion
Jun 2018
Completion
Jun 2018
Last update
Mar 14, 2025

Study contacts

Richard E Clark, MA MD
principal investigator · University of Liverpool

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.

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