In a study to be presented today at the 46th Annual Meeting of the American Society of Hematology in San Diego, Howard Hughes Medical Institute (HHMI) researchers at the University of California, Los Angeles, and colleagues at M.D. Anderson Cancer Center and Bristol-Myers Squibb in Princeton, NJ, report the first data from human clinical trials of the new compound, BMS-354825. Their studies indicate that the drug can successfully overcome Gleevec resistance in patients in the early stages of chronic myeloid leukemia. Patients enrolled in the study had experienced a worsening of the disease or intolerance when treated with Gleevec.
Study leader, HHMI investigator Charles L. Sawyers, Neil P. Shah, and colleagues at UCLA's Jonsson Comprehensive Cancer Center, report that BMS-354825 successfully circumvented Gleevec (imatinib) resistance in 85 percent of the 36 patients treated with the drug during phase I clinical trials at UCLA and M.D. Anderson Cancer Center. Resistance to Gleevec develops when patients acquire mutations in an enzyme that is targeted by Gleevec. Phase I clinical trials evaluate drug safety and toxicity at different dose levels in a small number of volunteers.
"Our study examined patients in all phases of CML, including the chronic phase, the accelerated phase, and blast crisis. The patients responded quite well to this new compound, and we observed no side effects," said Sawyers. "In fact, the results of this clinical trial match very closely with what we would have predicted the outcome to be based on our earlier studies of this drug in mice."