Chronic phase Philadelphia chromosome-positive chronic myeloid leukemia
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
Concentration numb
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Available for periodic follow-up 2) Life expectancy of at least approximately 3 months 3) ECOG performance status score 0-1 4) 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: • 600 mg/day AND developed progressive disease while receiving imatinib at that dose. B. CML with resistance to imatinib =600 mg/d with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib. C. Intolerant of imatinib at any dose. 6) Adequate hepatic function defined as: • total bilirubin = 2.0 times the institutional upper limit of normal • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times the institutional upper limit of normal 7) Adequate renal function defined as: • serum creatinine = 1.5 times the institutional upper normal limit 8) Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the lower limit of normal. 9) Men and women, ages 18 years of age or older. 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
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 of at least 1 month before and at least 3 months after completion of the study medication. 3) Previous diagnosis of accelerated phase or blast crisis CML 4) Subjects who are eligible and willing to undergo transplantation during the screening period 5) A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. 6) Uncontrolled or significant cardiovascular disease 7) History of significant bleeding disorder unrelated to CML, 8) Concurrent incurable malignancy other than CML. 9) Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy 10) 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, d) any other investigational or antineoplastic agent other than hydroxyurea or anagrelide within 4 weeks before starting treatment with BMS-354825 11) Subjects currently taking drugs that are generally accepted to have a risk of causing Torsade de Pointes. 12) Subjects taking medications that irreversibly inhibit platelet function 13) Subjects taking medications known to be potent CYP3A4 inhibitors or inducers 14) Prior therapy with BMS-354825.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to estimate the major cytogenetic response (MCyR) rate to BMS-354825 in subjects with Philadelphia chromosome positive chronic phase Ph+ CML who have disease that is resistant to high dose imatinib (primary resistance, acquired resistance or mutation highly associated with imatinib resistance).;Secondary Objective: 1) To estimate the MCyR rate in the imatinib-intolerant subjects. 2) To assess the durability of MCyR and time to MCyR in the imatinib-resistant and the imatinib-intolerant groups 3) To estimate complete hematologic response (CHR) rate, duration of CHR and time to CHR in the imatinib-resistant and the imatinib-intolerant groups 4) To estimate major molecular response rate in the imatinib-resistant and the imatinib-intolerant groups 5) To assess the health-related quality of life using the FACT-G 6) To assess further the safety and tolerability of BMS-354825 7) 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 of this Phase II study is to estimate MCyR rate to BMS- 354825 in treated subjects with chronic phase Ph+ CML who have resistance to high dose imatinib (primary resistance, acquired resistance or mutation highly associated with imatinib resistance). Secondary endpoints include duration of MCyR, time to MCyR, complete hematologic response (CHR) rate, duration of CHR, time to CHR, major molecular response rate and BCR/ABL mutational analysis, in addition to health-related quality of life, safety and collection of samples to contribute to population pharmacokinetic modeling. A separate calculation of response rates will be performed for the imatinib-intolerant group at the time of the primary analysis for the imatinib-resistant subjects. Safety: Evaluation of safety will be a secondary endpoint of this study. For safety evaluation, toxic effects will be a | — |
Countries
Austria, Denmark, Finland, Germany, Ireland, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed