Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study).

Background: Even though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2-3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma. However, prospective randomized trials including allogeneic stem cell transplantation as second-line therapy do not exist to date and therefore urgently needed to demonstrate the value of this therapy in the overall setting of patients with multiple myeloma.

Methods: This clinical trial is a national, multicenter, randomized, open labeled phase III study conducted in 30 hospitals spread all over Germany. After study inclusion, all patients will receive 3 cycles of salvage therapy with one of the currently approved triplet regimens for first relapse. After 3 cycles of salvage therapy, remission status will be assessed. If the patient achieves at least stable disease, partial or complete remission and an HLA compatible stem cell donor could be identified, he/she will be randomized (1:1) to the control or interventional study arm. Approximately 400 patients will be enrolled to enable a randomization of 280 patients. The primary endpoint is overall survival at five years after randomization. The main secondary objectives and endpoints are progression-free survival rate, time-to first occurrence of an infection with CTCAE grade 3-5, non-relapse mortality rate and incidence of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation.

Discussion: The present clinical study is designed to evaluate the superiority of allogeneic stem cell transplantation compared to conventional therapy (triplet chemotherapy) for the difference in overall survival at 5 years, toxicity and quality of life in patients with multiple myeloma who have relapsed or progressed after first-line autologous stem cell therapy.

Trial Registration: ClinicalTrials.gov (NCT05675319) registered on January 9, 2023.