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Chronic Myeloid LeukaemiaPhase 2DESTINYNCT01804985

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

A Phase 2 study testing Imatinib, nilotinib and dasatinib in people with Chronic Myeloid Leukaemia, run by University of Liverpool at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukaemia
What is being tested?
Imatinib, nilotinib and dasatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
174 participants
Where
1 siteUnited Kingdom
Study dates
Dec 2013to Jun 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • CML in first chronic phase.
  • Demonstration of BCR-ABL1 positivity at/shortly after original diagnosis.
  • Written Informed Consent
  • Must have received TKI treatment for at least 3 years.
  • 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.

Who cannot join

  • Age under 18
  • Life expectancy predicted to be less than 37 months because of intercurrent illness
  • Presence of serious concomitant illness (e.g. heart, renal, respiratory or active malignant disease) that might preclude completion of the trial
  • CML in accelerated phase or blast crisis at any time
  • Any molecular result during the preceding 12 months that is not in either MMR or MR4.
  • Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) twice or more because of intolerance
Show all 11Show fewer
  • 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.
  • 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.
  • 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.
  • Pregnant or lactating women
  • 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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • University of Liveprool

    Liverpool, L69 3GL

Other trials in United Kingdom

About this study

Official title: A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy

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.

Being tested
Imatinib, nilotinib, dasatinib
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ImatinibDrug

    Also called Glivec or Gleevec

    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;

  • nilotinibDrug

    Also called Tasigna

    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);

  • dasatinibDrug

    Also called Sprycel

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

Study groups in NCT01804985
Study groupRoleWhat they receive
De-escalated TreatmentExperimentalImatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months
Receives: Drug: Imatinib; Drug: nilotinib; Drug: dasatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 37months

Secondary outcomes (5)

  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

    Measured: 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

    Measured: 37 months

  3. • Quality of Life

    • Quality of Life

    Measured: 37 months

  4. • Health Economic Assessment

    • Health Economic Assessment

    Measured: 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.

    Measured: 37 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionJun 2018
  4. Study completionJun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
174 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01804985
Sponsor's protocol ID
4203
Acronym
DESTINY
Status last verified
Sep 2018
First submitted
3 Mar 2013
Last updated
14 Mar 2025
Results posted
No
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imatinib, nilotinib and dasatinib in people with Chronic Myeloid Leukaemia, run by University of Liverpool at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01804985, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.

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