Myeloid Blast Phase Chronic Myeloid Leukemia
Conditions
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects with Ph+ (or BCR/ABL+) myeloid blast phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate. Subjects are considered to have myeloid blast phase CML if they meet at least one of the following criteria: • = 30% myeloid blasts in peripheral blood or in bone marrow • Extramedullary infiltrates of leukemic cells (other than in spleen or liver) with eripheral blood myeloid blast morphology 2) ECOG performance status score 0 - 2 (See Appendix 1) 3) 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 4) Adequate renal function defined as: • serum creatinine = 1.5 times the institutional upper normal limit 5) 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. 6) Men and women, 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 for at least 3 months after completion of the study medication. 3) Subjects who are eligible and willing to undergo transplantation during the screening period. 4) A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. 5) Uncontrolled or significant cardiovascular disease 6) Subjects who received: - imatinib mesylate within 7 days - interferon or cytarabine within 14 days - a targeted small molecule anti-cancer agent within 14 days, - any other investigational or antineoplastic agent other than hydroxyurea within 28 days before starting treatment with BMS-354825 7) Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes 8) Subjects taking medications that irreversibly inhibit platelet function 9) Prior therapy with BMS-354825.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to estimate the major and overall hematologic response rates to BMS-354825 in myeloid blast phase CML subjects with primary or acquired resistance to imatinib mesylate. The major hematologic response rate is defined as the proportion of all treated subjects with best response of complete hematologic response (CHR) or no evidence of leukemia (NEL). Overall hematologic response (OHR) rate is defined as the proportion of treated subjects with best response of major or minor hematologic response.;Secondary Objective: 1) To assess the durability of hematologic response and time to hematologic response (major and overall) in the imatinib resistant group. 2) To assess cytogenetic and molecular responses in the imatinib resistant group. 3) To measure the minor hematologic response rate in the imatinib resistant group. 4) To assess hematologic, cytogenetic and molecular responses in the imatinib intolerant group. Further, durability and time to hematologic response will be assessed. 5) To explore the role of BCR-ABL mRNA expression and point mutations in the BCR-ABL gene as predictors or surrogates of response. 6) To measure health-related quality of life (HRQOL) using the FACT-G. 7) To assess further the safety and tolerability of BMS-354825. 8) To assess the pharmacokinetics of BMS-354825 given every 12 hours on a continuous daily dosing schedule. 9) Population PK will be performed on samples from the initial 60 treated subjects.;Primary end point(s): Efficacy The co-primary endpoints in this study are the major hematologic response rate and the overall hematologic response (OHR) rate in the imatinib resistant group. The major hematologic response rate is defined as the proportion of all treated subjects with best response of major hematologic response. The OHR rate is defined as the proportion of all treated subjects with best response of major or minor hematologic response. The secondary efficacy endpoints include | — |
Countries
Denmark, Finland, Italy, Sweden, United Kingdom
Outcome results
None listed