GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS Study

Status:	Recruiting
Conditions:	Hospital
Therapuetic Areas:	Other
Healthy:	No
Age Range:	Any - 17
Updated:	12/12/2018
Start Date:	December 5, 2018
End Date:	December 5, 2021
Contact:	Mark W Hall, MD
Email:	mark.hall@nationwidechildrens.org
Phone:	614-722-3438

GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS (GRACE)

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.

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

We found this trial at

sites

Children's Hospital Colorado

13123 E 16th Ave
Aurora, Colorado 80045

(720) 777-1234