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

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.

Study Overview

• Status: Completed
• Conditions: Pediatric Sepsis-induced MODS
• Intervention / Treatment: Drug: GM-CSF

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Mattel Children's Hospital
    • San Francisco, California, United States, 94158
      • Benioff Children's Hospital/UCSF
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV GM-CSF 125 mcg/m2/dose; 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; 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: Leukine; granulocyte macrophage colony-stimulating factor
Experimental: SQ GM-CSF 125 mcg/m2/dose; 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; 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: Leukine; granulocyte macrophage colony-stimulating factor
Experimental: IV GM-CSF 250 mcg/m2/dose; 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; 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: Leukine; granulocyte macrophage colony-stimulating factor
Experimental: SQ GM-CSF 250 mcg/m2/dose; 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; 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: Leukine; granulocyte macrophage colony-stimulating factor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Investigators: Principal Investigator: Mark W Hall, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Actual): December 5, 2023
• Study Completion (Actual): December 5, 2023

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; sepsis; GM-CSF; MODS; immunoparalysis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Multiple Organ Failure; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors
• Other Study ID Numbers: GRACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After subject enrollment and follow up have been completed, the DCC will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers.
• IPD Sharing Time Frame: After subject enrollment and follow up have been completed. Data will be available indefinitely.
• IPD Sharing Access Criteria: The public use dataset will be available through the CPCCRN website
• IPD Sharing Supporting Information Type: ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No