A Randomized Multi-center Open Label Study of BMS-354825 vs.Imatinib Mesylate (Gleevec) 800 mg/d in Subjects with Chronic Phase PhiladelphiaChromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistantto Imatinib at a Dose at 400 - 600 mg/dProtocol version 3.0 dated 18-Nov-04, andCountry-specific Amendment 01 version 2.0 dated 28-Apr-05
- Conditions
- Chronic phase Philadelphia-Chromosome Positive (Ph+) Chronic Myeloid leukemia (CML)
- Registration Number
- EUCTR2004-004450-96-ES
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
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:
• < 15% blasts in peripheral blood and in bone marrow
• < 20% basophils in peripheral blood
• < 30% blasts + promyelocytes in peripheral blood and in bone marrow
• Platelets = 100,000/mm3 unless thrombocytopenia is due to recent therapy
• No extramedullary involvement (other than liver or spleen)
4- Subjects must fulfill all of the following criteria relating to prior treatment with
imatinib:
A. Has not previously been treated with imatinib at a dose greater than 600 mg/day
B. Developed resistance to disease while receiving an imatinib dose 400-600 mg/day
C. Able to tolerate chronic administration of imatinib at the highest dose the subject
has received in the past
5- 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
6- Adequate renal function defined as:
• serum creatinine = 1.5 times the institutional upper normal limit
7- 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.
8- 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
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 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method