2nd or 3rd TKI-stop After 2 Years Nilotinib Pre-treatment in CML-patients

• Status: Active, not recruiting
• Trial end date: 2027-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The main goal of the study is the assessment of duration of major molecular response (MMR) or better at 12 and 36 months after stopping tyrosine kinase inhibitors (TKI) therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 (BCR-ABL ratio <0,01% on international Scale (IS) for at least one year and MR4.5 (BCR-ABL ratio <0,0032% on IS) for at least 6 months:

• who failed a first stop in the EURO-SKI study (standardized criteria)

• who failed a first or second stop outside the EURO-SKI study but would have had fulfilled same eligible criteria and were stopped according to EURO-SKI rules

• who failed a first or second stop outside the EURO-SKI study without fulfilling EURO-SKI rules

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European LeukemiaNet
• Collaborators: Heidelberg University; Ludwig-Maximilians - University of Munich

Criteria

Inclusion Criteria:

• Age ≥ 18 years

• Patients with Ph chromosome and/or the BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML

• CML in CP having failed a prior attempt to stop imatinib or other TKIs therapy either within EURO-SKI or not

• Pretreatment at least one year with any TKI after 1st stop

• Written informed consent

Exclusion Criteria:

• Previous hematological relapse after first stop of TKI.

• Failure to any TKI at any time during CML treatment according to current 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 (≥ 10 Points)

• Impaired cardiac function including any of the following:

• 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