Chronic myelogenous leukemia (CML) MedDRA version: 17.0 Level: LLT Classification code 10009012 Term: Chronic myelogenous leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: BOSUTINIB
Product Code: SKI-606
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BOSUTINIB
Current Sponsor code: SKI-606
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Wyeth Pharmaceuticals Inc, a wholly owned subsidiary of Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 USA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cytogenetic diagnosis of chronic phase Ph+ CML diagnosed for = 6 months. 2. Diagnosis of chronic phase as defined (prior to any anti-cancer treatment) by all of the following: a. =65 years) yes F.1.3.1 Number of subjects for this age range 57
Exclusion criteria
Exclusion criteria: 1. Philadelphia chromosome negative CML. 2. Prior anti-leukemia treatment. Up to six months of prior hydroxyurea or anagrelide treatment is allowed. 3. Identified stem cell donor with transplant planned within 12 months of randomization. 4. Prior stem cell transplant 5. Central nervous system (CNS) leukemia. (Subjects with symptoms of CNS leukemia must have a negative lumbar puncture prior to randomization) 6. Extramedullary disease only 7. History of accelerated or blast phase CML. 8. Major surgery or radiotherapy within 14 days of randomization. 9. Concomitant use of or need for medications known to prolong the QT interval 10. History of clinically significant or uncontrolled cardiac disease including: • history of or active congestive heart failure • uncontrolled angina or hypertension within 3 months • myocardial infarction (within 12 months) • clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). • diagnosed or suspected congenital or acquired prolonged QT syhistory of or prolonged QTc • unexplained syncope 11. Prolonged QTc (> 0.45; average of triplicate readings at screening) 12. Recent or ongoing clinically significant gastrointestinal disorder. 13. Female subjects who are pregnant or breastfeeding. 14. Known seropositivity to HIV, current acute or chronic hepatitis B (hepatitis B surface antigen positive), hepatitis C, or cirrhosis. 15. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months. 16. Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the QT interval. 17. History of radiation therapy to greater than 25% of bone marrow. 18. Congenital or acquired cytopenia predating CML diagnosis (e.g. congenital neutropenia or immune thrombocytopenia). 19. Unstable or severe uncontrolled medical condition, evidence of serious active infection, significant psychiatric illness, or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk associated with the subject’s participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the rate of complete cytogenetic response (CCyR) at one year in chronic phase subjects receiving bosutinib alone versus chronic phase subjects receiving imatinib alone. ;Secondary Objective: Estimate the major molecular response (MMR) rate at one year. Estimate the duration of CCyR, CHR, and MMR. Estimate the time to transformation to accelerated phase (AP) and blast phase (BP). Assess the population PK of bosutinib. Assess comparative safety of bosutinib vs. imatinib;Primary end point(s): The primary efficacy endpoint is Complete Cytogenetic Response (CCyR) at one year (48 weeks). The CCyR will be assessed for subjects in both arms via cytogenetic analysis conducted by labs local at study sites. To ensure reliable estimation of cytogenetic response, the cytogenetic assessment must have 20 or more metaphases. For post-baseline cytogenetic assessments, if fewer than 20 metaphases are available, then FISH analysis of bone marrow or peripheral blood, for the presence of Bcr-Abl fusion product, will be used if at least 200 cells are analyzed. In this study, a CCyR at 1 year is counted only if the response is demonstrated at the one year visit (week 48); a CCyR gained and lost before the one year visit is deemed a non-response. Further details are outlined in the statistical analysis plan.;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Estimate the major molecular response (MMR) rate at one year. • Estimate the duration of CCyR, CHR, and MMR. • Estimate the time to transformation to accelerated and blast phases. • Assess the population PK of bosutinib. • Assess the comparative safety of bosutinib versus imatinib ;Timepoint(s) of evaluation of this end point: # 1 year (Estimate the major molecular response (MMR)) # End of Study (Estimate the duration of CCyR, CHR, and MMR) # End of Study (Estimate the time to transformation to accelerated and blast phases.) # 3 months(Assess the population PK of bosutinib) # 1 year and ongoing (Assess the comparative safety of bosutinib versus imatinib) | — |
Countries
Argentina, Belgium, Brazil, Canada, Chile, China, Colombia, France, Germany, Hong Kong, Hungary, India, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, Singapore, Slovenia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc
Outcome results
None listed