A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
- Conditions
- Adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)MedDRA version: 20.0 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.1 Level: PT Classification code 10009013 Term: Chronic myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2007-000208-34-FI
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 771
•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:
- < 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
•Adequate end organ function as defined by:
- total bilirubin < 1.5 x ULN
- SGOT and SGPT < 2.5 x ULN
- creatinine < 1.5 x ULN
- Serum amylase and lipase = 1.5 x ULN
- Alkaline phosphatase = 2.5 x ULN unless considered tumor related.
•Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug.
•Patients must have the following laboratory values (= LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication.):
•Potassium = LLN
•Magnesium = LLN
•Phosphorus = LLN
•Total calcium (corrected for serum albumin) = LLN
•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 747
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 99
•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 < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by locally read echocardiogram
- Inability to determine the QT interval on ECG
- Complete left bundle branch block
- Use of a ventricular-paced pacemaker
- Congenital long QT syndrome or a known family history of long QT syndrome.
- History of or presence of clinically significant ventricular or atrial tachyarrhythmias
- Clinically significant resting brachycardia (<50 beats per minute)
- QTc > 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 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 Appendix 14 for complete a list of these medications (this list may not be comprehensive). Novartis must be contacted if a patient needs to be started on any of these drugs during study treatment.
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