Prevention of Graft Rejection in Hematopoietic Stem Cell Transplant (HSCT) Recipients

Cincinnati Children's Hospital Medical Center

Status and phase: Enrolling; Early Phase 1

Conditions: Graft Failure; Hematopoietic Stem Cell Transplantation

Treatments: Drug: Emapalumab 3 mg/kg; Drug: Emapalumab 10 mg/kg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07244419

2024-0167

Details and patient eligibility

About

The investigators hypothesize that graft rejection after hematopoietic stem cell transplant (HSCT) is primarily driven by interferon gamma, and prophylactic interferon gamma inhibition in high-risk patients will prevent graft rejection. Additionally, knowledge of emapalumab PK/PD and in vitro mechanistic effects of emapalumab in this novel setting will guide optimization of dosing regimens and treatment approaches in future studies.

Full description

Graft rejection is a devastating and understudied complication of hematopoietic stem cell transplant (HSCT) due to the lack of available interventions outside of re-transplantation. Re-transplantation is challenging and is associated with increased morbidity and mortality.

The purpose of this study is to learn more about emapalumab and its ability to prevent graft rejection in hematopoietic stem cell transplant (HSCT) recipients. Specifically, the study doctors would like to learn more about the efficacy and treatment of emapalumab as a prophylactic intervention for graft rejection.

Enrollment: 20 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• All patients undergoing allogeneic HSCT at our institution will be evaluated for graft rejection risk factors. Patients deemed high risk for graft rejection will have 2 or more of the following: mismatched or haploidentical donor, ex vivo t-cell depleted graft, prior history of graft rejection.

Exclusion criteria

• Known hypersensitivity to any constituent of the study medication.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups

Emapalumab 3 mg/kg

Active Comparator group

Description:

Patients randomized to this arm will receive 3mg/kg of emapalumab intravenously (IV) once on day +1 after HSCT. Up to two additional, 10mg/kg rescue doses may be administered if patients developed signs and symptoms of acute graft rejection. Rescue dose administration decisions will be made in consultation with the lead study investigator. Emapalumab is a ligand-based therapy, which means high levels of circulating ligand (i.e. interferon gamma) will rapidly consume the drug. For these reasons, rescue doses may be given as early as 24 hours from the prior dose.

Treatment:

Drug: Emapalumab 3 mg/kg

Emapalumab 10 mg/kg

Active Comparator group

Description:

Patients randomized to this arm will receive 10mg/kg of emapalumab intravenously (IV) once on day +1 after HSCT. Up to two additional, 10mg/kg rescue doses may be administered if patients developed signs and symptoms of acute graft rejection. Rescue dose administration decisions will be made in consultation with the lead study investigator. Emapalumab is a ligand-based therapy, which means high levels of circulating ligand (i.e. interferon gamma) will rapidly consume the drug. For these reasons, rescue doses may be given as early as 24 hours from the prior dose.

Treatment:

Drug: Emapalumab 10 mg/kg