AUT study: Multicenter prospective trial after first or second unsuccessful treatment discontinuation in chronic myeloid leukemia estimating the efficacy of nilotinib in inducing the persistence of molecular remission after stopping TKI 2nd time or 3rd time
- Conditions
- chronic myeloid leukemia10024324
- Registration Number
- NL-OMON52992
- Lead Sponsor
- niversiteit van Heidelberg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
· Age >= 18 years
· Patients with Ph -chromosome and/or the BCR-ABL fusion gene (either b3a2
and/or b2a2) positive CML
· CML in CP having failed prior attempt(s) to stop imatinib or other TKIs
therapy either within EURO-SKI or not
· Pretreatment at least one year with any TKI after 1st or 2nd stop
· Written informed consent
· Previous hematological relapse after first or second stop of TKI.
· Failure to any TKI at any time during CML treatment TKI according to actual
ELN criteria
· Previous planned or performed allo SCT
· Previous AP/BC at any time in the history of the disease
· High cardiac risk according to ESC Score
· Contraindication against nilotinib (see following)
· Impaired cardiac function including any of the following:
o Use of a ventricular paced pacemaker; congenital long QT syndrome or
family history of; history or presence of significant ventricular or atrial
tachyarrhythmias; clinically significant resting bradycardia (<50 bpm); QTcF
>450 msec at baseline, myocardial infarction before baseline; other clinically
significant heart disease (e.g., unstable angina, congestive heart failure, or
uncontrolled hypertension).
· Treatment with inhibitors of CYP3A4 or medications that have been well
documented
to prolong the QT interval is contraindicated.
· History of acute pancreatitis within one year of study entry or medical
history of chronic pancreatitis.
· Positive hepatitis B virus serology test or HBV infection.
· Any other malignancy except if neither clinically significant nor requires
active intervention.
· Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, acute
or chronic liver disease, pancreatic, or severe renal disease unrelated to
tumor, active or uncontrolled infection).
· Women who are pregnant, breast feeding, or of childbearing potential without
a negative serum pregnancy test at baseline.
Male or female patients of childbearing potential unwilling to use an effective
barrier contraceptive method.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is molecular relapse-free survival, measured at 12 months<br /><br>and 36 months after 2nd stop or 3rd stop.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- number of patients who re-achieved stable MR4.5, and were proposed a 2nd stop<br /><br>or 3rd stop<br /><br>- number of patients who accepted/refused 2nd stop or 3rd stop 2 and 3 years<br /><br>after study entry; whereas stable MR4.5 is defined as two PCRs during 6 months<br /><br>before stopping demonstrating MR4.5<br /><br>- safety profile, tolerability and AEs under nilotinib treatment<br /><br>- QoL profiles under nilotinib treatment and comparison with previous TKI<br /><br>therapy before switch and after stopping<br /><br>- overall and progression-free survival, and probabilities of a restart of TKI<br /><br>treatment without prior molecular relapse<br /><br>- Time to re-achievement of MR4.5 after restart of therapy<br /><br>- incidence of any AEs (e.g. from musculoskeletal system) that arise after<br /><br>stopping TKI treatment a second time</p><br>