New agent shows promise in treatment-resistant CML
People with chronic myeloid leukemia (CML) are being enrolled in a phase 1 clinical trial to evaluate a tyrosine kinase inhibitor (TKI) that killed malignant CML cells and prolonged survival in a mouse model, and tamped down a mutant enzyme in human cells that led to relapse in treatment-resistant patients.
Like other TKI agents, such as imatinib, DCC-2036 blocks the action of BCR-ABL1—the abnormal enzyme that promotes the growth of CML cells. Approximately one-third of patients using imatinib will eventually relapse due to mutations that render BCR-ABL1 resistant to the TKI.
According to a statement issued by Tufts Medical Center, where DCC-2036 senior study author Richard Van Etten, MD, PhD, serves as director of the cancer center, patients who relapse after imatinib therapy are left with few treatment options other than bone marrow transplantation. Based on the results seen in his group's mouse model and experiments with human cells, Dr. Van Etten contends that DDC-2036 is “an excellent candidate for clinical development as a treatment for resistant CML.”
The DDC-2036 phase 1 clinical trial is now actively enrolling patients who have failed therapy with two other TKIs at Tufts Medical Center, M. D. Anderson Cancer Center, and University of Michigan Cancer Center. More information is available from the Neely Center for Clinical Cancer Research at Tufts Medical Center (617-636-5558) or http://clinicaltrials.gov/ct2/show/NCT00827138.
The study is sponsored by Deciphera Pharmaceuticals LLC (Lawrence, Kansas), and scientists from that company as well as from Emerald Biostructures (Bainbridge Island, Washington) were among Dr. Van Etten's coauthors for the Cancer Cell report (2011;19:556-568) describing the DCC-2036 findings to date.