Chronic phase Philadelphia-Chromosome Positive (Ph+) Chronic Myeloid leukemia (CML)
Conditions
Interventions
Product Name: BMS-354825-03
Product Code: BMS-354825-03
Pharmaceutical Form: Tablet
Current Sponsor code: BMS-354825-03
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- ECOG performance status score 0 - 1 (See Appendix 1) 2- Life expectancy of at least approximately 3 months 3-Subjects with chronic phase Ph+ CML, defined as a myeloproliferative disorder with evidence of a Philadelphia chromosome on cytogenetic analysis. Subjects meeting all of the following criteria will be classified as having chronic phase CML: • =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1- Women who are pregnant or breastfeeding 2- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period for at least 1 month before and for at least 3 months after completion of the study medication. 3- Prior treatment with imatinib at a dose > 600 mg 4- Subjects who have previously identified BCR-ABL mutation in the following list will be excluded (L248V, G250E, Q252H/R, Y253H/F, E255K/V, T3151/D, F317L, H369P/R). 5- Previous diagnosis of accelerated phase or blast crisis CML. 6- Intolerance to imatinib at any dose. 7- Subjects who are eligible and willing to undergo transplantation during the screening period 8- A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy. 9- Uncontrolled or significant cardiovascular disease. 10-Uncontrolled hypertension 11- History of significant bleeding disorder unrelated to CML. 12- Subjects who received a) imatinib within 7 days b) interferon or cytarabine within 14 days c) a targeted small molecule anti-cancer agent within 14 days, any other investigational or antineoplastic agent other than hydroxyurea or anagrelide within 28 days before starting treatment with BMS-354825 13- Subjects currently taking the drugs that are generally accepted to have a risk of causing Torsade de Pointes 14- Subjects taking medications that irreversibly inhibit platelet function. 15- Prior therapy with BMS-354825. 16- Subjects taking medications known to be potent CYP3A4 inhibitors or inducers 17-Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations unrelated to CML that, in the judgment of the Investigator, would jeopardize subject safety during participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1) To estimate the MCyR at any time (prior to crossover) in both treatment arms 2) To assess the durability of major cytogenetic response and time to MCyR prior to cross over in both treatment arms 3) To estimate complete hematologic response (CHR) rate prior to crossover in both treatment arms. 4) To assess the durability of CHR and time to CHR prior to crossover in both treatment arms 5) To estimate major molecular response rates by measuring BCR-ABL transcripts in blood during treatment using quantitative RT-PCR prior to crossover 6) To estimate post-crossover efficacy endpoints in subjects who cross over 7) To assess the health-related quality of life in both treatment arms prior to crossover using the FACT-G 8) To assess further the safety and tolerability of BMS-354825 9) To collect blood samples for pharmacokinetic analysis of BMS-354825 given BID that will contribute to population pharmacokinetic modeling.;Primary end point(s): Efficacy The primary endpoint in this study is MCyR rates, at 12 weeks, to BMS-354825 and to imatinib at 800 mg daily. MCyR rate at 12 weeks is defined as the proportion of all randomized subjects at 12 weeks with best response of complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). The secondary efficacy endpoints include MCyR rate at any time prior to cross over, CHR rates, duration of MCyR and CHR, time to MCyR and CHR prior to crossover for both arms. Safety/Toxicity Analysis of safety will be performed on the dataset of all treated patients, by arm as treated for events that have occurred prior to crossover. In addition, safety analyses will be conducted for events that have occurred after crossover on the dataset of subjects that have crossed-over to Imatinib and, separately, on the dataset of subjects that have crossed over to BMS-354825. Descriptive statistics will be employed in the analysis of all safety and laboratory observations in this study. Other secondary endpoints incl | — |
Countries
Austria, Denmark, Estonia, Finland, Germany, Hungary, Ireland, Spain, Sweden, United Kingdom
Outcome results
None listed