NCT02799147

GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

Dose-escalation Study of Graft-versus-host Disease Prophylaxis With High-dose Post-transplantation Bendamustine in Patients With Refractory Acute Leukemia

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: St. Petersburg State Pavlov Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. Additional immunosuppression could be added for mismatched grafts.

Conditions

• Leukemia, Acute Lymphoblastic
• Acute Myeloid Leukemia
• Mixed-Lineage Acute Leukemias

Interventions

Type	Name	Description
PROCEDURE	Allogeneic stem cell transplantation
DRUG	Fludarabine monophosphate
DRUG	Busulfan
DRUG	Bendamustine

Timeline

• Start date: 2016-06-01
• Primary completion: 2020-11-01
• Completion: 2020-11-01
• First posted: 2016-06-14
• Last updated: 2020-11-23

Locations

1 site across 1 country: Russia