Nilotinib for Chronic myeloid leukaemia (in remission)|Chronic myeloid leukaemia

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Patients with Ph chromosome and/or the BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML"}
• {"criterion_text":"- CML in CP having failed prior attempt(s) to stop imatinib or other TKIs therapy either within EURO-SKI or not"}
• {"criterion_text":"- Pretreatment at least one year with any TKI after 1st or 2nd stop, respectively"}
• {"criterion_text":"- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Previous hematological relapse after first or second stop of TKI"}
• {"criterion_text":"- Any other malignancy except if neither clinically significant nor requires active intervention"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Failure to any TKI at any time during CML treatment according to current ELN criteria"}
• {"criterion_text":"- Previous planned or performed allo SCT"}
• {"criterion_text":"- Previous AP/BC at any time in the history of the disease"}
• {"criterion_text":"- High cardiac risk according to ESC score (≥ 10 points)"}
• {"criterion_text":"- 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 tachyarrhythmia; • 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)."}
• {"criterion_text":"- Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval is contraindicated"}
• {"criterion_text":"- History of acute pancreatitis within one year of study entry or medical history of chronic pancreatitis"}
• {"criterion_text":"- Positive hepatitis B virus serology test or HBV infection"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is molecular relapse-free survival, measured at 12 months and 36 months after 2nd or 3rd stop.","definition_or_measurement_approach":"Molecular relapse-free survival measured at 12 months and 36 months after the 2nd or 3rd TKI stop (time-to-event assessment at those time points)."}

Secondary endpoints

• {"endpoint_text":"- overall survival and progression-free survival probabilities","definition_or_measurement_approach":"Overall survival and progression-free survival probabilities (time-to-event analyses)."}
• {"endpoint_text":"- Estimation of the number of patients in MR4.5 who would be eligible for stopping TKI therapy","definition_or_measurement_approach":"Estimation/count of patients in MR4.5 eligible for stopping TKI."}
• {"endpoint_text":"- The number of patients who regain MR4 and MR4.5 and the time to MR4 recovery","definition_or_measurement_approach":"Count of patients regaining MR4 and MR4.5 and time-to-recovery measurements."}
• {"endpoint_text":"- Outcome of molecular relapse-free survival at 12, 18, 24 and 36 months after TKI discontinuation","definition_or_measurement_approach":"Molecular relapse-free survival assessed at 12, 18, 24 and 36 months after discontinuation (time-point analyses)."}

Other endpoints

• {"endpoint_text":"- Explorative objective: of clinical and biological factors correlating with reaching MR4.5 or better on nilotinib treatment after 1st or 2nd unsuccessful stopping;","definition_or_measurement_approach":"Exploratory analysis of clinical and biological correlates with achievement of MR4.5 on nilotinib."}
• {"endpoint_text":"- Explorative objective: Evaluation of medico-economic impact of stopping TKI a second or third time.","definition_or_measurement_approach":"Exploratory medico-economic evaluation of stopping TKI a second or third time."}

Germany

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

27-11-2024

Processing Time Days

9

Number Of Sites

5

Number Of Participants

75

Primary sponsor

Full Name

Heidelberg University

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Novartis Pharma GmbH","duties_or_roles":"Source of monetary support","organisation_type":""}