A phase II multi-center, open-label, study of Nilotinib at a dose of 300mg twice daily in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) - ICORG 08-02
- Conditions
- Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)MedDRA version: 14.1 Level: LLT Classification code 10058246 Term: Chronic myelogenous leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2008-004551-30-GB
- Lead Sponsor
- ICORG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 40
• Male or female patients = 18 years of age
• ECOG performance status 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:
1. <15% blasts in peripheral blood and bone marrow
2. <30% blasts plus promyelocytes in peripheral blood and bone marrow,
3. <20% basophils in the peripheral blood,
4. =100 x 109/L (=100,000/mm3) platelets
5. No evidence of extramedullary leukemic involvement, with the exception of
hepatosplenomegaly.
• Adequate end organ function as defined by:
1. total bilirubin <1.5xULN
2. AST and ALT <2.5xULN
3. estimated GFR of = 30 ml/min
4. Serum amylase and lipase =1.5xULN
5. Aklaline phosphatase = 2.5 xULN 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 (=(lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication:-
1. Potassium =LLN
2. Magnesium = LLN
3. Phosphorous = LLN
4. 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
• Patients who are considered Ph- because they do not have a confirmed cytogenetic diagnosis of Philadelphia Chromosome with (9,22) translocation
• Previously documented T315I mutations
• Any previous exposure to dasatinib or any other medical treatment for CML. Exceptions are imatinib which will be allowed for up to 2 weeks and Hydroxyurea and Anagrelide which will be allowed for up to 4 weeks.
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 echocardiogram
*Inability to determine the QT interval on ECG
*Complete left bundle branch block
*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 three serial baseline ECG (using the QTcF formula). If QTcF>450msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-scanned for QTc.
*History of clinically documented myocardial infarction within past 12 months
*History of unstable angina (during the last 12 months)
*Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
• History of significant congenital or acquired bleeding disorder unrelated to cancer.
• Major surgery within 4weeks 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
• Patients with other primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
• 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. The Principal Investigator 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 inducers, (e.g. Dexamethasone, 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. The Principal Investigator must be contacted if a patient needs to be started on any of these drugs during study treatment.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ul
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