SummaryThe Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi‐arm randomized phase II trial evaluating novel salvage therapies compared with R‐GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)‐eligible patients with relapsed/refractory diffuse large B‐cell lymphoma (RR‐DLBCL). This component of the LY.17 trial evaluated a dose‐intensive chemotherapy approach using a single cycle of inpatient R‐DICEP (rituximab, dose‐intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol‐specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R‐DICEP or to 3 cycles of R‐GDP. The overall response rate (ORR) was 65.6% for R‐DICEP and 48.6% for R‐GDP. The ASCT rate was 71.9% versus 54.3%, and 1‐year progression‐free survival rate was 42% versus 32%, respectively, for R‐DICEP versus R‐GDP. Although the improvement in ORR for R‐DICEP versus R‐GDP exceeded the pre‐specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3–5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents.