NCT06235398

Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 50 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Three recent prospective "transplant/no transplant" studies concluded to an advantage of OS with transplantation in patients with high or intermediate-2 IPSS risk (not significant in Kröger's study). No prospective randomized trial has assessed the pre-transplant therapy in MDS patients yet but some information can be extracted from these 3 recent studies. In the French study (n=162), 72% patients with a donor received HSCT, previously treated by hypomethylating agent (HMA) in 71% of them. There was a trend to a better survival in patients achieving a complete remission with pre-graft therapy (HR: 0.55, p=0.088) and higher risk of death in unresponsiveness patients transformed into AML (HR: 2.36, p=0.008). In Nakamura's study (n=384), 83% of patients with a donor were transplanted, previously treated by HMA in 68%2. The multivariable Cox model for Overall Survival (OS) and Leukemia-free survival showed an excess risk in patients treated by HMA. Moreover, responders still have a higher risk of mortality as compared to patients who did not receive any pre-graft therapy (HR: 2.417, p=0.0054). In the German study, the aim was to initiate azacytidine at inclusion and to transplant patients after 4 cycles if a donor was identified1. Among 170 registered patients, 162 initiated 5-aza but 36% of them were "lost during this pre-graft therapy" before allocation to "donor" or "no-donor" arm, for different reasons including death (n=12). After 4 cycles of 5-aza, 79/81 patients "donor arm" were transplanted. The multivariable analysis showed remission status did not influence OS. Those 3 previous clinical trials thus suggest that a substantial number of patients planned for transplantation are not transplanted nowadays while no evidence of HMA benefit before HSCT has been clearly identified. This phase 2 study aim to assess the feasibility of upfront HSCT in patients with high risk MDS in order to increase the probability to be transplanted and to achieve a subsequent remission and better survival.

Conditions

• Myelodysplastic Syndromes

Interventions

Type	Name	Description
BIOLOGICAL	Hematopoietic stem-cell transplantation	Upfront related donor transplantation

Timeline

• Start date: 2024-02-01
• Primary completion: 2028-02-01
• Completion: 2028-02-01
• First posted: 2024-01-31
• Last updated: 2024-01-31