Subjects with Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia who are resistant or intolerant to Imatinib Mesylate
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects with a myeloproliferative disorder defined as Ph+ (or BCR/ABL+) CP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate are eligible. Subjects can be pretreated with IFN, standard chemotherapy or high-dose chemotherapy and stem-cell transplantation. Subjects considered to have Ph+ (or BCR/ABL+) CP CML must meet all the following criteria: • =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 one month before and for at least 3 months after completion of the study medication. 3) Women with a positive pregnancy test on enrollment or prior to study drug administration. 4) Subjects eligible for immediate autologous or allogeneic stem cell transplantation. 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 (see Protocol section 5.2 for details) 7) History of significant bleeding disorder unrelated to CML 8) Clinically significant bleeding from the GI tract within 6 months 9) Concurrent incurable malignancy other than CML 10) Dementia or altered mental status that would prohibit the understanding or rendering of informed consent 11) Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy 12) Subjects who received any of the following: • imatinib mesylate within 7 days • interferon or cytarabine within 7 days • a targeted small molecule anti-cancer agent within 7 days • any other investigational or any antineoplastic agent other than hydroxyurea (HU) within 28 days 13) Subjects currently taking the following drugs that are generally accepted to have a risk of causing Torsades de Pointe (see Protocol section 5.2 for details) 14) Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of BMS-354825. 15) Subjects taking medications that irreversibly inhibit platelet function or anticoagulants Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of BMS-354825 as defined by MCyR when administered QD relative to BMS-354825 administered BID in the treatment of CP CML imatinib-resistant subjects. The QD schedule will be considered efficacious if it can be demonstrated that the true 6-month MCyR rate is no more than 15% less than that of the BID schedule.;Secondary Objective: The main secondary objective is to estimate the difference of MCyR rates between the two TDD levels (MCyRR100 mg TDD minus MCyRR140 mg TDD) in the imatinib-resistant subjects. Other secondary objectives are: 1) In the imatinib-resistant subjects, by TDD, schedule and arm • To estimate the rate of MCyR and CHR • To estimate the time to, and duration of MCyR and CHR • To evaluate PFS and OS 2) In the imatinib-intolerant subjects • To assess efficacy (MCyR and CHR) 3) In all treated subjects • To assess the safety of BMS-354825 by TDD, schedule and arm • To compare the rates of specific adverse events (e.g. fluid retention, pleural/pericardial effusion, myelosuppression, and dose reduction due to toxicity) between the two schedules and two TDD • To collect PK data and Heath Utility measurements by arm • To describe the spectrum of mutation and to explore the level of expression of the BCR-ABL gene;Primary end point(s): Efficacy: The primary efficacy endpoint is the rate 6-month of MCyR. Secondary efficacy endpoints include the rate of CHR, time to, and duration of MCyR and CHR, PFS and OS. Definitions of response and progression are detailed in Section 3.3 of the Protocol. Safety/Toxicity: Toxic effects will be assessed continuously. Safety and tolerability of BMS-354825 will be reported for all randomized subjects. Adverse events and other symptoms will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Other Endpoints: Additional secondary endpoints include the collection of pharmacokinetics (PK) data and Health Utility measurements, and the explora | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Germany, Hungary, Ireland, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed