Description:
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).
Title
- Brief Title: De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia
- Official Title: A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy
Clinical Trial IDs
- ORG STUDY ID:
4203
- NCT ID:
NCT01804985
Conditions
- Chronic Myeloid Leukaemia
Interventions
Drug | Synonyms | Arms |
---|
Imatinib | Glivec or Gleevec | De-escalated Treatment |
nilotinib | Tasigna | De-escalated Treatment |
dasatinib | Sprycel | De-escalated Treatment |
Purpose
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).
Detailed Description
The next definitive 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.
Trial Arms
Name | Type | Description | Interventions |
---|
De-escalated Treatment | Experimental | Imatinib, nilotinib or dasatinib; de-escalated to half the standard dose for 12 months | - Imatinib
- nilotinib
- dasatinib
|
Eligibility Criteria
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:
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
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 |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | • 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 |
Safety Issue: | |
Description: | • 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 |
Measure: | • Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI |
Time Frame: | 37 months |
Safety Issue: | |
Description: | • Proportion of patients who lose their MMR on de-escalation/stopping and regain MMR on resumption of their TKI |
Measure: | • Quality of Life |
Time Frame: | 37 months |
Safety Issue: | |
Description: | • Quality of Life |
Measure: | • Health Economic Assessment |
Time Frame: | 37 months |
Safety Issue: | |
Description: | • Health Economic Assessment |
Measure: | • Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation. |
Time Frame: | 37 months |
Safety Issue: | |
Description: | • Lab studies to define subsets of patients who are more likely to relapse on de-escalation / cessation. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | University of Liverpool |
Last Updated
May 4, 2017