A phase III multi-center, open-label, randomized study of the efficacy 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. - CAMN107A2302

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005047-26-BE
• Date of registration: 24/08/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services
• Public title: A phase III multi-center, open-label, randomized study of the efficacy 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. - CAMN107A2302
• Scientific title: A phase III multi-center, open-label, randomized study of the efficacy 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. - CAMN107A2302
• Date of first enrolment: 15/10/2007
• Target sample size: 586
• 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: yes 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 and female patients = 18 years of age.
ECOG performance status of 0,1, or 2.
Diagnosis of Ph+ CML-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
=100 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.
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.

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 mutation.
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 dosing of 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 of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; ST depression > 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; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant resting brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock, bifascicular block; myocardial infarction = 3 months; uncontrolled angina; 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 (see Concomitant Therapy section in protocol).



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

Health Condition(s) or Problem(s) studied

Nilotinib will be evaluated in patients having showed a suboptimal cytogenetic response to imatinib

Intervention(s)

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

Trade Name: Glivec 400 mg
Product Name: Glivec
Pharmaceutical Form: Film-coated tablet
Other descriptive name: Glivec
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Glivec 100 mg
Product Name: Glivec
Pharmaceutical Form: Film-coated tablet
Other descriptive name: Glivec
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: To evaluate the rate of major molecular response (MMR) of nilotinib compared to imatinib in adult patients with Ph+ CML in CP at 12 months.

To evaluate the rate of complete molecular response (CMR) of nilotinib compared to imatinib in adult patients with Ph+ CML in CP at 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.

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

Main Objective: To evaluate the complete cytogenetic response (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.

Secondary ID(s)

CAMN107A2302