A Randomized Multi-Center Open Label Study of BMS-354825 vs Imatinib Mesylate (Gleevec®) 800 mg/d in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to Iamtinib at a Dose of 400-600 mg/d
OBJECTIVES:
Primary
- Determine the 12-week major cytogenetic response (MCyR) rate in patients with imatinib
mesylate-resistant Philadelphia chromosome-positive chronic phase chronic myelogenous
leukemia treated with BMS-354825 vs imatinib mesylate.
Secondary
- Determine the MCyR rate prior to crossover in patients treated with these drugs.
- Determine the durability of MCyR and time to MCyR prior to crossover in patients
treated with these drugs.
- Determine the complete hematologic response (CHR) rate prior to crossover in patients
treated with these drugs.
- Determine the durability of CHR and time to CHR prior to crossover in patients treated
with these drugs.
- Determine the major molecular response rate prior to crossover, as determined by
BCR-ABL transcripts in blood during treatment using quantitative reverse transcriptase
polymerase chain reaction, in patients treated with these drugs.
- Determine post-crossover efficacy endpoints in patients treated with these drugs who
crossover.
- Assess health-related quality of life prior to crossover in patients treated with these
drugs.
- Determine the safety and tolerability of BMS-354825 in these patients.
- Determine the pharmacokinetics of BMS-354825 in these patients.
OUTLINE: This is an open-label, multicenter, randomized, crossover study. Patients are
stratified according to study site and cytogenetic response to prior imatinib mesylate (yes
vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral BMS-354825 twice daily in the absence of disease
progression or unacceptable toxicity. Patients experiencing disease progression or
persistent intolerance to BMS-354825 cross over to arm II after a 2-day washout period.
After crossover, patients receive oral imatinib mesylate twice daily in the absence of
further disease progression or unacceptable toxicity.
- Arm II: Patients receive oral imatinib mesylate twice daily in the absence of disease
progression or unacceptable toxicity. Patients experiencing disease progression,
intolerance to imatinib mesylate, lack of major cytogenetic response at 12 weeks, or <
30% absolute reduction in Philadelphia chromosome-positive metaphases at 12 weeks cross
over to arm I after a 1-week washout period. After crossover, patients receive oral
BMS-354825 twice daily in the absence of further disease progression or unacceptable
toxicity.
Quality of life is assessed at baseline, at day 29, every 4 weeks for 24 weeks, every 12
weeks for the remainder of study treatment, and then at the completion of study treatment.
After the completion of study treatment, patients are followed for at least 30 days.
PROJECTED ACCRUAL: A minimum of 150 patients (100 in arm I and 50 in arm II) will be accrued
for this study within 6-12 months.
Interventional
Masking: Open Label, Primary Purpose: Treatment
Major cytogenic response (MCyR) rate at 12 weeks
No
Ronald Paquette, MD
Principal Investigator
Jonsson Comprehensive Cancer Center
United States: Federal Government
CDR0000428457
NCT00112775
March 2005
Name | Location |
---|---|
Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |