A phase III multi-center, open label, randomised study of optimised imatinib versus nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)
- Conditions
- Chronic myeloid leukemia (CML)10024324
- Registration Number
- NL-OMON45211
- Lead Sponsor
- ovartis Pharma BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
* 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.
*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 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 complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm. Novartis must be cont
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the MMR, rate at 12 months of nilotinib at two different strengths<br /><br>with that of Gleevec. Efficacy measurements will be done on peripheral blood<br /><br>samples by quantitative RT-PCR.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Rate, time to and duration of MMR (* 4 log reduction/* 4.5 log reduction in<br /><br>BCR-ABL transcript levels), complete cytogenetic response (CCyR), hematologic<br /><br>response, pharmacokinetics, overall survival, PFS and EFS will be calculated<br /><br>for efficacy.<br /><br><br /><br>Safety will be evaluated using assessments of (serious) adverse events (using<br /><br>CTCAE grading), laboratory parameters, physical examinations, echocardiograms<br /><br>and ECG monitoring.</p><br>