A phase III randomized, open-label, multi-center study of nilotinib versus imatinib in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have suboptimal cytogenetic response (CyR) on imatinib - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005047-26-IT
• Date of registration: 15/10/2007
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A phase III randomized, open-label, multi-center study of nilotinib versus imatinib in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have suboptimal cytogenetic response (CyR) on imatinib - ND
• Scientific title: A phase III randomized, open-label, multi-center study of nilotinib versus imatinib in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have suboptimal cytogenetic response (CyR) on imatinib - ND
• Date of first enrolment: 25/09/2007
• Target sample size: 608
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005047-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Greece, Hungary, Italy, Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female patients >= 18 years of age. ECOG performance status of 0, 1, or 2. Diagnosis of Ph+ CML in CP defined as: <15% blasts in peripheral blood and bone marrow < 30% blasts plus promyelocytes in peripheral blood and bone marrow < 20% basophils in the peripheral blood >=x 109 /L (>= 100,000 /mm3) platelets No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly Patients with suboptimal cytogenetic response to a dose of at least 400 mg imatinib defined as >= 6 to < 12 months of treatment and have 36 - 95% Ph+ metaphases, or >=12 to <=18 months of treatment and have 1 - 35% Ph+ metaphases. Bone marrow karyotyping is required. FISH analysis is not allowed. Total bilirubin <1.5XULN; SGOT and SGPT <2.5XULN; creatinine < 1.5XULN, potassium and magnesium >=LLN or correctable with supplements. Serum amylase and lipase <= 1.5xULN, alkaline phosphatase <= 2.5XULN unless considered tumor related. Ability to provide written informed consent prior to any study related screening procedures being performed.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Prior accelerated phase or blast phase CML. Previously documented T315I mutations. Achieved prior PCyR or CCyR and lost that response prior to entering the study. Presence of chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+. Patients who have received more than 18 months of imatinib therapy. Intolerance to imatinib 400 mg/day defined as the inability to maintain at least 400 mg daily for the previous 3 months. Previous treatment with any other tyrosine kinase inhibitor except imatinib. Impaired cardiac function including any one of the following: LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) by echocardiography Complete left bundle branch block ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads Congenital long QT syndrome or family history of long QT syndrome History of or presence of significant ventricular or atrial tachyarrhythmias Clinically significant resting brachycardia (<50 bpm) QTcF > 450 msec on baseline ECG Right bundle branch block plus left anterior hemiblock, bifascicular block Myocardial infarction within one year of baseline visit Unstable angina diagnosed or treated within the past 12 months Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with antihypertensives). Treatment with strong inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval is contraindicated (please see Section 6.6.4 for further guidance). Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery). History of acute pancreatitis within one year of study entry or medical history of chronic pancreaitis. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). Any other malignancy that is clinically significant or requires active intervention. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). History of significant congenital or acquired bleeding disorder unrelated to cancer. Previous radiotherapy to >= 25% of the bone marrow. Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery. Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon). Treatment with other investigational agents within 30 days of Day 1 (first dose of study drug). History of non-compliance to medical regimens or inability to grant consent. 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 effective barrier contraceptives throughout the trial and for 3 months following discontinuation of study drug. Post-menopausal women must be ammenorrheic for at least 12 months to be considered of non-childbearing potential.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Myelogenous Leukemia (CML) Ph+ chronic phase
MedDRA version: 6.1 Level: PT Classification code 10009013

Intervention(s)

Product Name: imatinib
Product Code: STI571
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: IMATINIB
Product Code: STI571
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To evaluate the CCyR rate at 12 months of nilotinib compared to imatinib in adult patients with Ph+ CML in CP who have a suboptimal cytogenetic response to imatinib.

Primary end point(s): CCyR rate at 12 months (CCyR is defined as 0% Ph+ metaphases)

Secondary Objective: To evaluate the rate of major molecular response (MMR) of nilotinib compared to imatinib in adult patients with Ph+ CML in CP after 12 months. To evaluate the rate of complete molecular response (CMR) of nilotinib compared to imatinib in adult patients with Ph+ CML in CP after 12 months. To evaluate the time to and duration of CCyR of nilotinib compared to imatinib in adult patients with Ph+ CML in CP. To evaluate the time to and duration of MMR of nilotinib compared to imatinib in adult patients with Ph+ CML in CP. To evaluate the time to and duration of CMR of nilotinib compared to imatinib in adult patients with Ph+ CML in CP. To describe overall survival and progression-free survival up to 5 years in adult patients with Ph+ CML in CP. To evaluate the safety profile of nilotinib compared to imatinib in adult patients with Ph+ CML in CP.

Secondary ID(s)

2005-005047-26-BE

CAMN107A2302