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.
- Conditions
- ilotinib will be evaluated in patients having showed a suboptimal cytogenetic response to imatinib
- Registration Number
- EUCTR2005-005047-26-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 608
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 400 mg imatinib (1st line therapy) 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 rquired on a min. of 20 metaphases. FISh analysis is not allowed.
The following laboratory results must be present:
Total bilirubin <1.5XULN; SGOT and SGPT <2.5XULN; Creatinine < 1.5XULN, Serum potassium, phosphorus, magnesium and calcium = LLN or correctable with supplements prior to the first doese of study drug. 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
Prior accelerated phase or blast phase CML.
Previously documented T315I mutation.
Achieved prior PCyR or CCyR on imatinib and lost that response prior to entering the study.
• Prior treatment with > 400 mg/day of imatinib.
• 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 400 mg daily for the previous 3 months.
• Previous treatment with any other tyrosine kinase inhibitor except imatinib.
• Patients who had any other treatment for CML (e.g. interferon, transplant) except
hydroxyurea and/or anagrelide.
•Impaired cardiac function including any one of the following:
• LVEF < 45% by echocardiography
• Complete left bundle branch block
• 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 screening ECG (using the QTcF formula). If QTc > 450 and
electrolytes are not with normal ranges, electrolytes should be corrected and then the patient rescreened for QTc
• Use of a ventricular-paced pacemaker
• Myocardial infarction within one year of the first dose of study drug
• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled
hypertension, unstable angina).
• Treatment with strong inducers (e.g., dexamethasone, phenytoin, carbamazepine,
rifampin, rifabutin, rifapentin, phenobarbitol, St John’s Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See link in Section 6.6.4 for complete list of these medications.
• Treatment with strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See link in Section 6.6.4 for complete list of these medications.
• Treatment with medications that have been well documented to prolong the QT interval is contraindicated. 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 pancreatitis.
• 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 chronic liver disease, pancreatic, or severe renal disease unrelated to tumor, active or uncontrolled infection).
• History of significant congenital or acquired bleeding disorder unrelated to cancer.
• Previous radiotherapy to = 25% of the bone marrow.
• Patients who have had major surgery within 4 weeks prior to the first dose of study drug or who have not recovered from prior surgery.
• Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon).
• Treatment with other investigational agents within 28 days of Day 0 (first dose of
study drug).
• History of non-compliance to medical regimens or inability to grant consent.
• Wo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method