DESTINY

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).

This study is active but no longer recruiting

Verified: January 2014 by University of Liverpool

Sponsor: University of Liverpool

Collaborators

• Newcastle University
• Imperial College London
• University of Glasgow

Information provided by (Responsible Party): Professor Richard E Clark, University of Liverpool

• First received: March 3, 2013
• Last updated: January 9, 2014
• Last verified: January 2014

Primary Outcome Measures

• 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: 37 months ] [ Designated as safety issue: No ]
• 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

• 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 ] [ Designated as safety issue: No ]
• 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 lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI [ Time Frame: 37 months ] [ Designated as safety issue: No ]
• Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI

Estimated Enrollment: 168

Detailed Description

The next definitive UK phase III trial in chronic myeloid leukaemia (CML) will be SPIRIT3, which will open in Summer 2014. 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.

Inclusion Criteria

• 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, 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, 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.

Contact

• Tony Coffey tony.coffey@liverpool.ac.uk
• Julie Perry julie.perry@liverpool.ac.uk

SPIRIT 3

The next definitive UK phase III trial in chronic myeloid leukaemia (CML) will be SPIRIT3, which will open in the first quater of 2015. 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.