Chronic Myeloid Leukemia (CML) MedDRA version: 20.0 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Bosulif 100mg film coated tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Bosutinib
CAS Number: 380843-75-4
Current Sponsor code: PF-05208763
SKI-606
Other descriptive name: SKI-606 monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Trade Name: Glivec
Pharmaceutical Form: Film-coated tablet
Sponsors
Pfizer Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Inclusion Criteria: 1. Molecular diagnosis of CP CML of = 6 months (from initial diagnosis). • Diagnosis of CP CML with molecular confirmation by detection of BCR-ABL rearrangement at screening (cytogenetic assessment for Philadelphia chromosome is not required for enrollment); diagnosis of CP CML will be defined as all of the following per ELN criteria: (a) =65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: Main Exclusion Criteria: 1. Any prior medical treatment for CML including tyrosine kinase inhibitors (TKIs) with the exception of hydroxyurea and/or anagrelide treatment which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject’s region. 2. Any past or current CNS involvement, including leptomeningeal leukemia. 3. Hypersensitivity to the active substance or to any of the following excipients: Microcrystalline cellulose (E460), croscarmellose sodium (E468), poloxamer 188, povidone (E1201), magnesium stearate (E470b), polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, Talc (E553b), iron oxide yellow (E172). 4. Extramedullary disease only. 5. Major surgery or radiotherapy within 14 days of randomization. 6. Concomitant use of or need for medications known to prolong the QT interval. 7. 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 history or prolonged QTc. (QTcF should not exceed 500 msec). • Unexplained syncope. 8.Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included. 9. Recent or ongoing clinically significant gastrointestinal (GI) disorder e.g. Crohn's Disease, Ulcerative Colitis or prior total or partial gastrectomy. 10. 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 12 months. 11. Uncontrolled hypomagnesemia or uncorrected hypokalemia, due to potential effects on the QT interval. 12. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial. 13. Women who are pregnant, planning to become pregnant during the study or are breastfeeding a child, or men who are planning to father a child during their participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of patients demonstrating Major Molecular Response (MMR) at 12 months (48 weeks) in the bosutinib arm with that of the imatinib arm in newly diagnosed Philadelphia chromosome positive (Ph+) chronic phase (CP) chronic myelogenous leukemia (CML) patients harbouring b2a2 and/or b3a2 transcripts.;Secondary Objective: Secondary: •To evaluate MMR by 18 months in the bosutinib treatment group compared with the imatinib treatment group. •To evaluate the duration of MMR in the bosutinib treatment group compared with the imatinib treatment group. •To estimate the proportion of patients demonstrating a cytogenic response (CCyR) by 12 months in both treatment groups. •To evaluate the duration of CCyR in both treatment groups. •To evaluate event free survival (EFS) in both treatment groups. •To evaluate overall survival (OS) in both treatment groups. •To assess the population pharmacokinetics (PK) of bosutinib administered once daily. •To assess correlations between trough concentrations of bosutinib and key efficacy and safety parameters. •To evaluate the safety profile of bosutinib and imatinib treatments. Please see protocol for exploratory endpoints;Primary end point(s): Efficacy: Primary Efficacy Endpoint: The primary efficacy endpoint is MMR at 12 months (48 weeks) in Ph+ CML patients harbouring b2a2 and/or b3a2 transcripts. • MMR is defined as =0.1% BCR-ABL on the international scale (IS) by real-time quantitative polymerase chain reaction (RQ-PCR). Safety: Safety will be assessed on an ongoing basis by physical examination including measurement of vital signs, laboratory assessments, standard safety evaluations (electrocardiograms [ECGs] for monitoring of QTc interval changes and echocardiograms/MUGA scans for monitoring ventricular function) and recording of adverse events (AEs) and serious adverse events (SAEs). Adverse events will be graded according to the NCI CTC version 4. Discontinuations due to AEs will be considered | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • MMR by 18 months. • Duration of MMR. • CCyR by 12 months . • Duration of CCyR. • EFS • OS Pharmacokinetic Endpoints • Population PK of bosutinib. • Correlations between trough concentrations of bosutinib and key efficacy and safety parameters.;Timepoint(s) of evaluation of this end point: Efficacy data: •MMR by 3, 6 and 9 months, MMR at 18 months and beyond 12 months. •Both = 4 and = 4.5 log reduction in BCR-ABL transcripts in bosutinib treatment group with imatinib at 3, 6, 9, 12 months and beyond 12 months. Pharmacokinetic Data (bosutinib treatment group only): A total of 4 PK samples per patient will be drawn. All patients will provide pre-dose blood samples on Day 1, Day 28, Day 56, and Day 84. | — |
Countries
Australia, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc
Outcome results
None listed