The program of developmental therapeutics addresses therapy for myeloma patients who have received prior treatment. Following 2 cycles of D.T. PACE, patients are randomized to either continuation with D.T. PACE or 2 cycles of high dose chemotherapy. In the event of failure to achieve complete response, patients are crossed-over. This project encompasses development of novel therapies along the lines of phase I and phase II evaluation. Arsenic trioxide, anti-TN receptor monoclonal antibody and other approaches are being evaluated.
Preliminary data are encouraging.
Preliminary data reveal that virtually all patients with myeloma exhibit at least a minor deletion of chromosome 13. Some have extensive deletions of not only one but both alleles. It is anticipated that critical regions on chromosome 13 can thus be defined, allowing for cloning of the postulated myeloma tumor suppressor genes and identification of their protein products. Extramural collaboration has been established with Dr. Malcolm Moore to determine the role of telomere length and telomerase activity both in myeloma progression and in the development of secondary myelodysplasia as a result of either chronic alkylating agent therapy or high dose therapy with acute stem cell renewal stress. Telomeres represent the distal parts of chromosomes, which require telomerase in the process of cell replication in order to conserve the integrity of chromosomes.