E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed Philadelphia chromosome and/or BCR-ABL positive CML in chronic phase in adult patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052065 |
E.1.2 | Term | Chronic phase chronic myeloid leukaemia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the rate of CMR after 18 months of nilotinib treatment |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the rate of annual progression and annual events at 12 and 24 months of treatment • To evaluate the rate of major molecular response at 12 and 24 months of treatment • To evaluate the rate of complete cytogenetic response at 12 and 24 months of treatment • To evaluate the rate of CMR at 12 and 24 months of treatment • To evaluate the annual rate of events in patients achieving a CMR at 12 months of treatment • To evaluate the Event-Free Survival (EFS) and Overall Survival (OS) at 12 months and at 24 months of treatment • To evaluate the safety and tolerability profile of nilotinib Exploratory objectives: • To identify the dynamics of molecular response and potential patterns • To evaluate the kinetics of MMR at 3, 6, 9, 12, 15, 18, 21 and 24 months of treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all inclusion criteria and none of the exclusion criteria to enter the study. Patients must meet all inclusion criteria within 4 weeks of enrollment (bone marrow examinations may be within 8 weeks) to enter the study. • Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome [t(9;22) translocation] (if the bone marrow sample is taken within 8 weeks of study start but before the patient consents, the bone marrow should not be repeated after the patient formally consents to the study) • Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR (Cross et al 1994) are eligible as well • Pretreatment with Hydroxyurea for a duration of up to 6 months is permitted as is treatment with Imatinib for up to 3 months The investigator should notify the DMC requesting review of any patient who has received prior imatinib treatment for 6 or more weeks to ensure that the patient is not failing on imatinib. • Age ≥ 18 years old (no upper age limit) • WHO performance status 0-2 • Normal serum levels ≥ LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin or phosphorus, or corrected to within normal limits with supplements, prior to the first dose of study medication • AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia • Total bilirubin ≤ 1.5 x ULN, except know Mb. Gilbert • Serum lipase and amylase ≤ 1.5 x ULN • Serum creatinine ≤ 1.5 x ULN • Written informed consent prior to any study procedures being performed |
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E.4 | Principal exclusion criteria |
• Known impaired cardiac function, including any of the following: • LVEF < 45% - Complete left bundle branch block - Right bundle branch block plus left anterior hemiblock, bifascicular block - Use of a ventricular-paced pacemaker - Congenital long QT syndrome - History of or presence of clinically significant ventricular or atrial tachyarrhythmias - Clinically significant resting bradycardia (<50 beats per minute) - QTc>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before Nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion. - Myocardial infarction with 12 months prior to starting Nilotinib - Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension) • History of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis • Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery) • Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/druglists/ printable-drug-list.cfm) • Concomitant medications known to be strong inducers or inhibitors of CYP450 isoenzyme CYP3A4: see link for complete list (http://medicine.iupui.edu/flockhart/table.htm) • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy • Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug • Treatment with any haematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 1 week prior to starting study drug • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention • Patients unwilling or unable to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate the rate of CMR after 18 months of study treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 331 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV. for details please refer to the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |