A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy
18 Years
N/A
Both
Chronic Myeloid Leukaemia
Trial Information
A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy
The next definitive UK phase III trial in chronic myeloid leukaemia (CML) will be SPIRIT3,
which will open in Summer 2013. 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.
Exclusion Criteria:
- Age under 18
- Life expectancy predicted to be less than 37 months because of intercurrent illness
(e.g. heart, renal, respiratory or active malignant disease) that might preclude
completion of the study
- 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.
- Treatment with higher than standard TKI doses ('standard' is defined as imatinib
400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily)
- Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
dasatinib) twice or more because of intolerance.
- Patients who switched previous licensed TKI treatment (imatinib, nilotinib or
dasatinib) because of resistance.
- 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.
- 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Outcome 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.
Outcome Time Frame:
37months
Safety Issue:
No
Principal Investigator
Richard E Clark
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Liverpool
Authority:
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study ID:
4203
NCT ID:
NCT01804985
Start Date:
July 2013
Completion Date:
July 2017
Related Keywords:
- Chronic Myeloid Leukaemia
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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