Adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) MedDRA version: 19.0 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification co
Conditions
Interventions
Trade Name: TASIGNA
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients ? 18 years of age • ECOG 0, 1, or 2. • Patients with CML-CP within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). Standard conventional cytogenetic analysis must be done on bone marrow. FISH cannot be used) • Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations (presence of BCR-ABL a review of a minimum 20 metaphases is required) • Documented chronic phase CML will meet all the criteria defined by: • =65 years) F.1.3.1 Number of subjects for this age range 99
Exclusion criteria
Exclusion criteria: •Patients who are considered Ph negative because they do not have a confirmed cytogenetic diagnosis of Philadelphia chromosome of (9,22) translocation. •Previously documented T315I mutations.•Treatment with tyrosine kinase inhibitor(s) prior to study entry is not allowed, except in the following situation: in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of Gleevec/Glivec at any dose may be prescribed to the patient but for no longer than 2 weeks in duration.•Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide•Impaired cardiac function including any one of the following:•LVEF 450 msec on the average of 3 serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc •History of clinically documented myocardial infarction•History of unstable angina (during the last 122 months)•Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).•Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).•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.•Treatment with other investigational agents within 30 days of Day 1.•History of non-compliance to medical regimens or inability to grant consent.•Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)•Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention • Patients actively receiving therapy with strong CYP3A4 inducers (e.g, dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John’s Wort) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm.Novartis must be contacted if a patient needs to be started on any of these drugs during study treatment. •Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the efficacy (MMR rate at 12 months) of nilotinib at 400mg BID with that of Gleevec/Glivec 400 mg QD in newly diagnosed, previously untreated Philadelphia chromosome-positive CML-CP patients. • To compare the efficacy (MMR rate at 12 months) of nilotinib at 300 mg BID with that of Gleevec/Glivec 400 mg QD in newly diagnosed, previously untreated Philadelphia chromosome-positive CML-CP patients. ; Secondary Objective: •To compare the rate of durable MMR at 24 months, which is defined as the proportion of patients who are in MMR at both 12 and 24 months and who have no confirmed loss of MMR in between those 2 time points, of nilotinib at 400 mg BID with that of Gleevec/Glivec 400 mg QD in newly diagnosed, previously untreated Philadelphia chromosome-positive CMLCP patients. •To compare the rate of durable MMR at 24 months of nilotinib at 300 mg BID with that of Gleevec/Glivec 400 mg QD in newly diagnosed, previously untreated Philadelphia chromosone-positive CML-CP patients. •To compare the rate of complete cytogenetic response (CCyR) in nilotinib treatment arms to Gleevec/Glivec in adult patients with Ph+ CML in CP at 12 months and beyond 12 months. •To evaluate the rate of MMR at 12 months between two nilotinib arms. • To evaluate the rate of MMR at 6 months and beyond 12 months in all three treatment arms. ;Primary end point(s): The primary efficacy endpoint is the rate of major molecular response (MMR) at 12 months after the start of first study medication as defined by = 3 log reduction of BCR-ABL transcript from standardized baseline or = 0.1% BCR-ABL/ABL% by international scale, measured by RQ-PCR. | — |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Colombia, Czech Republic, Denmark, Egypt, Finland, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Venezuela, Bolivarian Republic of
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed