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

NCT ID: NCT03769844

Last Updated: 2023-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-05

Study Completion Date

2023-12-05

Brief Summary

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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.

Detailed Description

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Conditions

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Pediatric Sepsis-induced MODS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

GM-CSF

Intervention Type 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.

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.

Group Type EXPERIMENTAL

GM-CSF

Intervention Type 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.

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.

Group Type EXPERIMENTAL

GM-CSF

Intervention Type 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.

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.

Group Type EXPERIMENTAL

GM-CSF

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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granulocyte macrophage colony-stimulating factor Leukine

Eligibility Criteria

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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
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nationwide Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Mark Hall

Professor, Department of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mark W Hall, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

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UCLA Mattel Children's Hospital

Los Angeles, California, United States

Site Status

Benioff Children's Hospital/UCSF

San Francisco, California, United States

Site Status

Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status

Children's National Medical Center

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

Site Status

Children's Hospital of Michigan

Detroit, Michigan, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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GRACE

Identifier Type: -

Identifier Source: org_study_id

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