GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS Study (GRACE)
Pediatric Sepsis-induced MODS
About this trial
This is an interventional treatment trial for Pediatric Sepsis-induced MODS focused on measuring sepsis, MODS, pediatric, immunoparalysis, GM-CSF
Eligibility Criteria
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
Sites / Locations
- UCLA Mattel Children's Hospital
- Benioff Children's Hospital/UCSF
- Children's Hospital of Colorado
- Children's National Medical Center
- Children's Hospital of Michigan
- Nationwide Children's Hospital
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
IV GM-CSF 125 mcg/m2/dose
SQ GM-CSF 125 mcg/m2/dose
IV GM-CSF 250 mcg/m2/dose
SQ GM-CSF 250 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.
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.
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.
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.