Clinical trial NCT03769844: GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS Study
Official title: GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS (GRACE)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pediatric Sepsis-induced MODS
Keywords: sepsis
MODS
pediatric
immunoparalysis
GM-CSF
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2018-12-10
Enrollment: 120
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is an open-label, sequential, dose- and route of administration-finding study that will be conducted in sequential cohorts of children with sepsis-induced MODS
Primary purpose: TREATMENT

Brief summary: This study is an open-label, multi-center, interventional trial in which children with sepsis-induced MODS undergo surveillance immune function testing beginning on Day 2 of MODS. Those children who demonstrate immunoparalysis (TNF-alpha response \<200 pg/ml) will receive a 7-day course of GM-CSF at a dose of 125 or 250 mcg/m2/day by either the intravenous (IV) or subcutaneous (SQ) route.

The goal of the study is to establish the dose and route of delivery that results in resolution of immunoparalysis (TNF-alpha response \>=200 pg/ml) by the morning after the 3rd scheduled dose with persistent resolution of immunoparalysis on the morning after the 7th scheduled dose. Resolution of immunoparalysis in 8 out of the first 10 subjects in a study treatment arm represents a successful dose and route. The goal of this study will be achieved through the following Specific Aims:

Specific Aim 1. Establish the immunologic efficacy of GM-CSF administered by the IV and SQ routes in children with immunoparalysis in the setting of sepsis-induced MODS.

Specific Aim 2. Estimate the pharmacokinetic parameters by the IV and SQ GM-CSF administered in pediatric sepsis-induced MODS.

Specific Aim 3. Demonstrate the feasibility of screening, enrollment, drug delivery, and sample collection for a multi-center immunostimulation trial in children with sepsis-induced MODS.


Eligibility criteria: Inclusion Criteria:

* \>= 40 weeks gestational age to \<18 years; AND
* Onset of \>=2 new organ dysfunctions (compared to pre-sepsis baseline) as measured by the Proulx criteria; AND
* Documented or suspected infection as the MODS inciting event.

Exclusion Criteria:

* Unable to collect a cumulative total of 20.5 mL of blood for this study due to research blood draw limits; OR
* Limitation of care order at the time of screening; OR
* Patients at high risk for brain death; OR
* Active (or planned within 7 days) immunosuppressive treatment for oncologic, transplant, or rheumatologic disease; OR
* Known primary immunodeficiency disorder; OR
* Diagnosis of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia;OR
* Known allergy to GM-CSF; OR
* Documented hyperferritinemia (serum ferritin \>= 500 ng/ml) during current sepsis event; OR
* Contraindication to SQ injection (ECMO); OR
* Burns where \>5% of the total body surface area is affected; OR
* Renal replacement therapy at the time of screening; OR
* On ECMO or anticipated to require ECMO; OR
* Known pregnancy; OR
* Inability to collect and ship sample for immune testing on MODS Day 2; OR
* Previous enrollment in the GRACE study

Primary outcomes:
measure: TNF-alpha response
timeFrame: Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Mattel Children's Hospital
state: California
city: San Francisco
country: United States
facility: Benioff Children's Hospital/UCSF
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Nationwide Children's Hospital
name: Mark W Hall, MD
role: PRINCIPAL_INVESTIGATOR
References: