Condition category
Cancer
Date applied
12/06/2013
Date assigned
12/06/2013
Last edited
23/01/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The purpose of this study is to investigate whether some patients, with excellent responses to treatment of white blood cell cancer [chronic myeloid leukaemia (CML)], are being over-treated and can remain well on either a lower dose of treatment or without treatment at all. The dose of drugs, imatinib (Glivec), nilotinib (Tasigna) or dasatinib (Sprycel), will initially be cut to half the standard dose for 12 months and then treatment will be stopped completely for a further two years. This study will also help to develop a treatment decrease and stopping strategy for future patients.

Who can participate?
Patients are eligible for DESTINY if, in the first phase, have been treated with imatinib, dasatinib or nilotinib for at least 3 years from original diagnosis and whose BCR-ABL1 levels (measure of a gene fusion product) have been at or below 0.1% on all tests for the past 12 months.

What does the study involve?
Two groups will be studied. Those in whom BCR-ABL1 has been undetectable for at least 12 months in at least 3 samples (molecular remission at the 4-log level, abbreviated as the MR4 group) and those in whom BCR-ABL1 is detectable on some or all tests in the past 12 months, but always below a level of 0.1% (major molecular response, abbreviated to the MMR group). Both MR4 and MMR groups will be treated identically though analysed separately, by initially decreasing treatment to half of the standard dose for 12 months. If the BCR-ABL1 level remains at or below 0.1%, treatment is then completely stopped and observation continues for a further 24 months.

What are the possible benefits and risks of participating?
It is estimated that DESTINY will bring substantial savings to the NHS. Dose decrease or discontinuation of treatment might improve quality of life. Imatinib has several mild but persistent side effects such as rash, oedema and stomach upset. Similarly, dasatinib may cause fluid accumulation in lungs and hypertension and nilotinib may be associated with an increased late risk heart diseases.

Where is the study run from?
1. The Royal Liverpool University Hospital, UK. (lead centre)
2. Cancer Research UK Liverpool Cancer Trials Unit (coordinating centre)

When is study starting and how long is it expected to run for?
Study Start Date: July 2013
Expected Recruitment End Date: July 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017

Who is funding the study?
Leukaemia & Lymphoma Research (UK)

Who is the main contact?
Tony Coffey
tony.coffey@liverpool.ac.uk

Trial website

http://www.lctu.org.uk/trial/trial_info.asp?id=101&tgcode=5&menuid=30

Contact information

Type

Scientific

Primary contact

Mr Tony Coffey

ORCID ID

Contact details

University of Liverpool Cancer Research Centre
200 London Road
Liverpool
L3 9TA
United Kingdom
-
tony.coffey@liverpool.ac.uk

Additional identifiers

EudraCT number

2012-004025-24

ClinicalTrials.gov number

NCT01804985

Protocol/serial number

14492

Study information

Scientific title

A trial of de-escalation and stopping treatment in chronic myeloid leukaemia patients with excellent responses to tyrosine kinase inhibitor therapy (De-Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in chronic myeloid leukaemia) (DESTINY)

Acronym

DESTINY

Study hypothesis

The DESTINY trial will evaluate the feasibility of de-escalation and then stopping treatment in chronic myeloid leukaemia patients with excellent responses to prior treatment. DESTINY is conceived as a pilot for including this strategy in the next phase III study for the UK (to be known as SPIRIT3). Patients are eligible if in first chronic phase; have been treated with imatinib, dasatinib or nilotinib for at least 3 years from original diagnosis; and whose BCR-ABL1 levels have been at or below 0.1% on all tests for the past 12 months. Two groups will be studied; those in whom BCR-ABL1 has been undetectable for at least 12 months in at least 3 samples, all of which have at least 104 control transcripts (molecular remission at the 4-log level, abbreviated as the ‘MR4’ group), and those in whom BCR-ABL1 is detectable on some or all tests in the past 12 months, but always below a level of 0.1% (major molecular response, abbreviated to the ‘MMR’ group). Both MR4 and MMR groups will be treated identically though analysed separately, by initially de-escalating treatment to 50% of the standard dose for 12 months. If the BCR-ABL1 level remains at or below 0.1%, treatment is then completely stopped, and observation continues for a further 24 months.

The objective of DESTINY is to determine the safety and efficacy of initially de-escalating and then stopping tyrosine-kinase inhibitor (TKI) treatment, in CML patients with either undetectable disease or with stable MMR.

Ethics approval

13/NW/0265; First MREC approval date 20/05/2013

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)

Intervention

Dasatinib, imatinib or nilotinib; de-escalated to half the standard dose for 12 months. If on imatinib, the dose should be decreased to 200mg daily, 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) and if on dasatinib then to 50 mg daily. Follow Up Length: 37 month(s).

Added 08/01/2014:
The study is co-sponsored between The University of Liverpool (see sponsor field below) and The Royal Liverpool and Broadgreen University Hospitals NHS Trust.

The Royal Liverpool and Broadgreen University Hospitals NHS Trust
Prescot Street
Liverpool
L7 8XP
UK
http://www.rlbuht.nhs.uk

Intervention type

Drug

Phase

Phase II

Drug names

Imatinib, nilotinib and sprycel

Primary outcome measures

Proportion of patients who can de-escalate and stop TKI without losing MMR. Timepoint(s): The proportion of patients who can first de-escalate their treatment (to half the standard dose)

Secondary outcome measures

1. Lab studies to define subsets of patients who are more likely to relapse on de-escalation/cessation; Timepoint(s): End of follow-up
2. Proportion of patients who can de-escalate but lose MMR on TKI cessation; Timepoint(s)
3. Proportion of patients who can successfully de-escalate their treatment (to half the standard dose o; Proportion of patients who lose MMR on de-escalation/stopping TKI but regain MMR on TKI resumption; Timepoint(s):
4. Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of Quality of Life; Timepoint(s): Baseline 1,2,3,6,9,12,13,14,16,19,22,25,29,33 & 37 months after trial entry

Overall trial start date

01/08/2013

Overall trial end date

01/08/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. CML in first chronic phase
2. Demonstration of BCR-ABL1 positivity at or 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):
5.1. (MR4 group) all the available BCR-ABL1 molecular results over the preceding 12 months are in MR4 (MR4 is defined as a BCRABL1/ABL1 ratio of zero, with at least 10,000 ABL1 control transcripts)
5.2. (MMR group) some or all BCR-ABL1 molecular results are in MMR (BCRABL1/ ABL1 ratio of 0.1% or less, 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.
* Patients who are Philadelphia chromosome (Ph) negative (or whose Ph status is not known) are eligible. Patients who do not have a standard BCR-ABL1 fusion transcript (i.e. other than e13a2 or e14a2, also known as b2a2 and b3a2) are eligible, but before screening the patient, contact should be made with Prof Foroni at Imperial College (see contacts) since specialised quantitative molecular assessment will be required.
Target Gender: Male & Female ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 168; UK Sample Size: 168; Description: 84 patients will be recruited from both the 'MR4' and 'MMR' groups of patients.

Participant exclusion criteria

1. Age under 18
2. Life expectancy is 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 study
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. Treatment with higher than standard TKI doses (‘standard’ is defined as imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily)
7. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) twice or more because of intolerance
8. Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) because of resistance
9. Patients treated with lower than standard TKI doses (imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily) 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
10. 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.
11. Pregnant or lactating women
12. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, 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.

Recruitment start date

01/08/2013

Recruitment end date

01/07/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Liverpool Cancer Research Centre
Liverpool
L3 9TA
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

Research and Business Services
The Forsight Centre
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Sponsor type

University/education

Website

http://www.liv.ac.uk

Funders

Funder type

Charity

Funder name

Leukaemia & Lymphoma Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes