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

NCT03769844 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: GRACE
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 8

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.

Conditions

Pediatric Sepsis-induced MODS

Keywords

sepsis; MODS; pediatric; immunoparalysis; GM-CSF

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Restoration of the TNF-alpha Response

  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

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

Study Arms (4)

IV GM-CSF 125 mcg/m2/dose

EXPERIMENTAL

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.

Drug: GM-CSF

SQ GM-CSF 125 mcg/m2/dose

EXPERIMENTAL

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.

Drug: GM-CSF

IV GM-CSF 250 mcg/m2/dose

EXPERIMENTAL

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.

Drug: GM-CSF

SQ GM-CSF 250 mcg/m2/dose

EXPERIMENTAL

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.

Drug: GM-CSF

Interventions

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.

Also known as: granulocyte macrophage colony-stimulating factor, Leukine

IV GM-CSF 125 mcg/m2/dose; IV GM-CSF 250 mcg/m2/dose; SQ GM-CSF 125 mcg/m2/dose; SQ GM-CSF 250 mcg/m2/dose

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \>= 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (8)

UCLA Mattel Children's Hospital

Los Angeles, California, 90095, United States

Location

Benioff Children's Hospital/UCSF

San Francisco, California, 94158, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Sepsis; Multiple Organ Failure

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; sargramostim

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Mark W. Hall, MD
• Organization: Nationwide Children's Hospital

mark.hall@nationwidechildrens.org

6147223438

Study Officials

• Mark W Hall, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Pediatrics

Model Details: 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

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 10, 2018
• Study Start: December 5, 2018
• Primary Completion: December 5, 2023
• Study Completion: December 5, 2023
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• Time Frame: After subject enrollment and follow up have been completed. Data will be available indefinitely.
• Access Criteria: The public use dataset will be available through the CPCCRN website

Locations

US (8)