SIGNIFICANT ONGOING CLINICAL TRIALS

Definitive, Late Phase Trials

Phase 3 Study of R-CHOP versus R-Dose-Adjusted-EPOCH with Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas

http://www.cancer.gov/clinicaltrials/CALGB-50303

This randomized trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL).

Specifically, this phase 3 trial, being led by the Cancer and Leukemia Group B (CALGB) and known as CALGB-50303, is testing R-CHOP (bolus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus R-DA-EPOCH (rituximab, dose-adjusted continuous infusion doxorubicin, vincristine, and etoposide with bolus cyclophosphamide and oral prednisone). R-CHOP is the standard of care in DLBCL but results in cure of 40 to 60 percent of patients. Evidence suggests that R-DA-EPOCH overcomes some of the biologically determined features of tumor resistance that limit R-CHOP effectiveness. This study has rigorous scientific endpoints that include acquisition of fresh tumor samples to conduct DNA microarray studies that have proven useful in determining lymphoma histogenetic origins associated with prognosis. In this manner, it may be possible to determine the subset of patients for whom R-DA-EPOCH confers superior treatment outcome so that patients at risk can be offered optimal therapy based on individual molecular diagnostic criteria. Additionally, this study is examining the use of positron emission tomography scanning with fluorodeoxyglucose (FDG-PET) as a biomarker of prognostic significance. Early FDG-PET normalization may indicate favorable outcome, whereas persistent FDG-PET abnormalities may indicate poor outcome. If confirmed, the advantage of a biomarker determination such as this would enable early treatment modifications for patients with suboptimal therapeutic effects, and this could potentially improve outcomes for these individuals. This study has important implications for further informing DLBC biology, treatment, and biomarker technology.