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

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.

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Key information

Conditions

Pediatric Sepsis-induced MODS Infections Inflammation Multiple Organ Failure Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Shock Systemic Inflammatory Response Syndrome

Age range

Up to 17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

UCLA Mattel Children's Hospital, Los Angeles, California, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

GM-CSF

Drug

Subjects demonstrating immunoparalysis (defined by a whole blood ex vivo LP-induced TNF-alpha production capacity < 200 pg/ml) will receive 7 days of GM-CSF treatment by either the IV or SQ route at a dose of either 125 or 250 mcg/m2/day for 7 days.

Other names: granulocyte macrophage colony-stimulating factor, Leukine

Primary outcomes

Number of Subjects With Restoration of the TNF-alpha Response

Time frame: Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS

Success in a cohort is defined as improvement in the whole blood ex vivo LPS-induced TNF-alpha production capacity (TNF response) to >= 200 pg/ml by the morning after the 3rd dose and persisting to the morning after the 7th dose in at least 8 out of 10 treated subjects within a cohort

Sponsors and collaborators

Lead sponsor

Nationwide Children's Hospital

Other

Registry information

Official study title

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

Acronym: GRACE

Important dates

Study start: 2018
Primary completion: 2023
Study completion: 2023
First posted: Dec 10, 2018
Registry last updated: May 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed