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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Stem Cell Transplantation; Graft Failure
• Intervention / Treatment: Drug: Emapalumab 3 mg/kg; Drug: Emapalumab 10 mg/kg

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jessica Anderson, BSN, RN, CCRC; Phone Number: 513-636-4200; Email: Jessica.Anderson@cchmc.org
• Study Contact Backup: Name: Manisha Pathak, MS; Phone Number: 513-636-4200; Email: Manisha.Pathak@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Jessica Anderson, BSN, RN, CCRC; Phone Number: 513-636-4200; Email: Jessica.Anderson@cchmc.org
      • Contact: Manisha Pathak, MS; Phone Number: 513-636-4200; Email: Manisha.Pathak@cchmc.org
      • Principal Investigator: Anthony Sabulski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Emapalumab 3 mg/kg; 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.	Drug: Emapalumab 3 mg/kg; Subjects will be randomized to either receive a 3mg/kg or 10mg/kg intravenous dose of emapalumab once and may receive up to two additional doses if clinical concern for impending graft rejection develops.
Active Comparator: Emapalumab 10 mg/kg; 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.	Drug: Emapalumab 10 mg/kg; Subjects will be randomized to either receive a 3mg/kg or 10mg/kg intravenous dose of emapalumab once and may receive up to two additional doses if clinical concern for impending graft rejection develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy of Emapalumab	Measured by the incidence of graft rejection in the treatment cohort.	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of emapalumab after 10 mg/kg prophylactic dosing	Measured by the Cmax (ng/mL) of emapalumab after 10mg/kg dose; Cmax values will be calculated using every 48 hour blood collections beginning at the time of emapalumab administration (day 1 after HSCT) until day 21.	Until day 42 or time of rescue dose, whichever is sooner
Maximum plasma concentration of emapalumab after 3 mg/kg prophylactic dosing	Measured by the Cmax (ng/mL) of emapalumab after 3 mg/kg dose; Cmax values will be calculated using every 48 hour blood collections beginning at the time of emapalumab administration (day 1 after HSCT) until day 21.	Until day 42 or time of rescue dose, whichever is sooner
Maximum plasma concentration of emapalumab after rescue dosing	Measured by the Cmax (ng/mL) of emapalumab after 10mg/kg rescue dose(s).; Cmax values will be calculated using every 48 hour blood collections beginning at the time of emapalumab rescue dose administration and continuing for 1 week after the rescue dose.	Until day 42 or 1 week after rescue dose, whichever is later
Number of patients in 10 mg/kg prophylactic dosing arm who maintain CXCL9 levels below the upper limit of normal for the test (</= 647 pg/mL).	Measured by plasma CXCL9 levels (pg/mL); CXCL9 levels will be measured every 48 hours beginning at the time of prophylactic emapalumab administration (day 1 after HSCT) and until day 21 after HSCT. Additionally, weekly CXCL9 levels will be obtained from day 21 until day 42 after HSCT.	Until day 42 or 1 week after rescue dose, whichever is later
Number of patients in 3 mg/kg prophylactic dosing arm who maintain CXCL9 levels below the upper limit of normal for the test (</= 647 pg/mL).	Measured by plasma CXCL9 levels (pg/mL); CXCL9 levels will be measured every 48 hours beginning at the time of prophylactic emapalumab administration (day 1 after HSCT) and until day 21 after HSCT. Additionally, weekly CXCL9 levels will be obtained from day 21 until day 42 after HSCT.	Until day 42 or 1 week after rescue dose, whichever is later
Number of patients in 10 mg/kg prophylactic dosing arm who maintain CXCL9 levels below 2.6x the upper limit of normal for the test.	Measured by plasma CXCL9 levels (pg/mL). This cutoff was chosen based on our prior publication which showed CXCL9 levels above this threshold were associated with graft rejection.; CXCL9 levels will be measured every 48 hours beginning at the time of prophylactic emapalumab administration (day 1 after HSCT) and until day 21 after HSCT. Additionally, weekly CXCL9 levels will be obtained from day 21 until day 42 after HSCT.	Until day 42 or 1 week after rescue dose, whichever is later
Number of patients in 3 mg/kg prophylactic dosing arm who maintain CXCL9 levels below 2.6x the upper limit of normal for the test.	Measured by plasma CXCL9 levels (pg/mL). This cutoff was chosen based on our prior publication which showed CXCL9 levels above this threshold were associated with graft rejection.; CXCL9 levels will be measured every 48 hours beginning at the time of prophylactic emapalumab administration (day 1 after HSCT) and until day 21 after HSCT. Additionally, weekly CXCL9 levels will be obtained from day 21 until day 42 after HSCT.	Until day 42 or 1 week after rescue dose, whichever is later
Emapalumab half-life after 10 mg/kg prophylactic dosing	Measured using the volume of distribution (L) and clearance (L/h) of emapalumab after 10mg/kg prophylactic dose; Half-life will be calculated using every 48 hour sample collections beginning at the time of emapalumab administration (day 1 after HSCT) until day 21. Additionally, weekly blood samples will be obtained from day 21 until day 42 after HSCT.	Until day 42 or time of rescue dose, whichever is sooner
Emapalumab half-life after 3 mg/kg prophylactic dosing	Measured using the volume of distribution (L) and clearance (L/h) of emapalumab after 3mg/kg prophylactic dose; Half-life will be calculated using every 48 hour sample collections beginning at the time of emapalumab administration (day 1 after HSCT) until day 21. Additionally, weekly blood samples will be obtained from day 21 until day 42 after HSCT.	Until day 42 or time of rescue dose, whichever is sooner
Emapalumab half-life after 10mg/kg rescue dosing	Measured using the volume of distribution (L) and clearance (L/h) of emapalumab after 10mg/kg dose(s); Half-life will be calculated using every 48 hour blood collections beginning at the time of emapalumab rescue dose administration and continuing for 1 week after the rescue dose.	Until day 42 or time of rescue dose, whichever is sooner
Overall survival	• Measured by overall survival of patients who receive prophylactic emapalumab.	100 days after HSCT.
Number of patients who develop infections	Measured by the incidence of infection in patients who receive prophylactic emapalumab.	100 days after HSCT.
Number of patients who develop mixed chimerism.	Measured by the incidence of mixed chimerism in patients who receive prophylactic emapalumab.	100 days after HSCT.

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Sobi, Inc.
• Investigators: Principal Investigator: Anthony Sabulski, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Emapalumab
• Other Study ID Numbers: 2024-0167

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No