GM-CSF for MODS (GRACE Trial)

Palo Alto (17 mi)

Overseen byMark W Hall, MD

Age: < 18

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Waitlist Available

Sponsor: Nationwide Children's Hospital

No Placebo Group

Prior Safety Data

Approved in 3 jurisdictions

Trial Summary

What is the purpose of this trial?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

Treatment Details

4Treatment groups

Experimental Treatment

Group I: SQ GM-CSF 250 mcg/m2/doseExperimental Treatment1 Intervention

If the SQ 125 mcg/m2/dose arm is not successful in a cohort of subjects (or if the IV dose had to be escalated to 250 mcg/m2/dose), we will transition to 250 mcg/m2/day via the SQ route for 7 consecutive days in a subsequent cohort.

Group II: SQ GM-CSF 125 mcg/m2/doseExperimental Treatment1 Intervention

Subjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the subcutaneous (SQ) route at a dose of 125 mcg/m2/day for 7 consecutive days.

Group III: IV GM-CSF 250 mcg/m2/doseExperimental Treatment1 Intervention

If the IV 125 mcg/m2/dose arm is not successful in the first cohort of subjects, we will transition to 250 mcg/m2/day via the IV route for 7 consecutive days in a subsequent cohort.

Group IV: IV GM-CSF 125 mcg/m2/doseExperimental Treatment1 Intervention

Subjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the intravenous (IV) route at a dose of 125 mcg/m2/day for 7 consecutive days.

GM-CSF is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Leukine for: