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| Name | Class |
|---|---|
| Sobi, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Emapalumab 3 mg/kg | Active Comparator | 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. |
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| Emapalumab 10 mg/kg | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emapalumab 3 mg/kg | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary efficacy of Emapalumab | Measured by the incidence of graft rejection in the treatment cohort. | 100 days |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of emapalumab after 10 mg/kg prophylactic dosing |
| Until day 42 or time of rescue dose, whichever is sooner |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jessica Anderson, BSN, RN, CCRC | Contact | 513-636-4200 | Jessica.Anderson@cchmc.org | |
| Manisha Pathak, MS | Contact | 513-636-4200 | Manisha.Pathak@cchmc.org |
| Name | Affiliation | Role |
|---|---|---|
| Anthony Sabulski, MD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital Medical Center | Recruiting | Cincinnati | Ohio | 45229 | United States |
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| ID | Term |
|---|---|
| C000644327 | Emapalumab |
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| Emapalumab 10 mg/kg | Drug | 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. |
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| Maximum plasma concentration of emapalumab after 3 mg/kg prophylactic dosing |
| Until day 42 or time of rescue dose, whichever is sooner |
| Maximum plasma concentration of emapalumab after rescue dosing |
| 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). |
| 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). |
| 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. |
| 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. |
| Until day 42 or 1 week after rescue dose, whichever is later |
| Emapalumab half-life after 10 mg/kg prophylactic dosing |
| Until day 42 or time of rescue dose, whichever is sooner |
| Emapalumab half-life after 3 mg/kg prophylactic dosing |
| Until day 42 or time of rescue dose, whichever is sooner |
| Emapalumab half-life after 10mg/kg rescue dosing |
| 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. |