NCT04395222

Tocilizumab for the Prevention of Graft Failure and GVHD in Haplo-Cord Transplantation

A Prospective Study of Tocilizumab for the Prevention of Graft Failure and Graft-versus-Host Disease in Haplo-Cord Transplantation

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety of reducing and ultimately eliminating anti-thymocyte globulin (ATG) from the haplo-cord transplant conditioning regimen and replacing it with tocilizumab, an IL-6 receptor monoclonal antibody, to improve immune reconstitution and reduce relapse while preserving low rates of graft failure and graft versus host disease (GVHD).

Detailed description

This study is a prospective phase II non-inferiority study investigating tocilizumab as a potential alternative to anti-thymocyte globulin (ATG) in haplo-cord transplantation. It is a single-center study based at Weill Cornell Medicine/NewYork Presbyterian Hospital. The hypothesis is that tocilizumab is a safe and effective alternative to ATG in haplo-cord transplantation, facilitating transient engraftment of the haplo-identical stem cell graft without prolonged neutropenia or second nadir prior to durable cord engraftment while also preventing graft versus host disease (GVHD). This study plans to enroll patients with hematologic malignancies in need of alternate donor transplant. All subjects will be conditioned with fludarabine, melphalan and total body irradiation (TBI), followed by a single dose of tocilizumab 8 mg/kg on Day -1. Patients will be enrolled into 4 successive cohorts, initially administering the current standard 3 doses of ATG 1.5 mg/kg (total 4.5 mg/kg). In the absence of safety signals, we will drop one dose of ATG in successive cohorts until the drug ultimately has been eliminated. The primary endpoint of the study is successful haplo-derived neutrophil engraftment. Treatment will only be of interest if there is evidence that this rate is greater than 60%. If there are 4 or fewer successes, that dose group will be deemed unacceptable and the next higher ATG dose for which there were 5 or more success will be expanded.

Conditions

• Hematologic Malignancy
• Bone Marrow Transplant

Interventions

Type	Name	Description
DRUG	Tocilizumab	Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen
DRUG	Fludarabine	Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.
DRUG	Melphalan	Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.
DRUG	Anti-thymocyte globulin (rabbit)	Anti-thymocyte globulin (ATG) 1.5 mg/kg
RADIATION	Total Body Irradiation	Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

Timeline

• Start date: 2020-10-07
• Primary completion: 2022-09-28
• Completion: 2027-06-01
• First posted: 2020-05-20
• Last updated: 2026-01-06
• Results posted: 2023-10-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study