Ignite Creation Date:
2024-05-06 @ 3:11 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04549285
Status:
WITHDRAWN
Last Update Posted:
2021-09-14
First Post:
2020-09-08
Brief Title:
Infusions of Mesenchymal Stromal Cells in Children With Multisystem Inflammatory Syndrome
Sponsor:
Joanne Kurtzberg MD
Organization:
Duke University
Study Overview
Official Title:
A Phase I Pilot Study of the Safety of Infusions of Allogeneic Human Cord Tissue Mesenchymal Stromal Cells in Children With Multisystem Inflammatory Syndrome in Children MIS-C
Status:
WITHDRAWN
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MISTIC
Brief Summary:
The purpose of this multi-site pilot study is to test whether infusions of human cord tissue mesenchymal stromal cells hCT-MSC are safe in children with multi system inflammatory syndrome MIS-C We will also describe the symptom course and duration of this hyper-inflammatory syndrome in these patients Six patients less than 21 years old with MIS-C that is refractory to intravenous immune globulin IVIG andor steroids will be given intravenous infusions of hCT-MSCs Doses of 2x106 cellskg up to a maximum dose of 100x106 cells will be given on days 1 2 3 -7 day 7 is optional Participants will be followed up to 90 days after administration for severe adverse events and survival Safety will be evaluated through adverse event monitoring clinical evaluations ie vital signs physical examinations laboratory tests ie hematology serum chemistries and urinalysis and cardiac function ie echocardiogram ECG from the signing of informed consent and throughout the patients participation in this treatment protocol
Detailed Description:
This phase I multisite pilot study will test whether infusions of human cord tissue derived MSCs hCT-MSC are safe in children with multisystem inflammatory syndrome MIS-C
The study population will consist of six patients 18 to 21 years old with a life expectancy 72 hours and COVID-19 related MIS-C that is refractory to treatment with intravenous immune globulin IVIG
Multisystem inflammatory syndrome in children MIS-C is a newly recognized serious hyper-inflammatory syndrome that is occurring in small numbers of children many of whom are within a month or so of recovering from a COVID-19 infection While the clinical presentation varies affected patients are typically previously healthy individuals who are less than 21 years of age The diagnostic criteria include fever laboratory evidence of inflammation and multisystem involvement requiring hospitalization Up to 75 of patients present with an element of cardiogenic shock requiring inotropic support with some also requiring intubation with mechanical ventilation Reported supportive treatments have included intravenous immune globulin IVIG tocilizumab methylprednisolone and aspirin In the limited cases reported up to 50 of children with MIS-C have antibodies to COVID-19 in their blood and may or may not be PCR positive on a nasal swab or throat culture The disease is incompletely understood but currently believed at least in part to be a hyper-immune response to a recent COVID-19 infection
In laboratory experiments MSCs have been shown to inhibit T-cell proliferation and decrease production of pro-inflammatory cytokines In animal models up to 70 of infused cells are engulfed by lung macrophages leading to secretion of anti-inflammatory molecules by these macrophages These observations have led to the hypothesis that MSCs may work through both anti-inflammatory immune-modulatory and regenerative mechanisms
Over the past several months MSCs have been tested in small cohorts of adult patients with COVID-19 Acute Respiratory Distress Syndrome to determine if the cytokine storm hypothesized to cause this complication could be suppressed by MSCs Early results are encouraging and formal clinical trials are underway Extending this work into the pediatric population the hypothesis of this study is that infusion of hCT-MSC can reverse the pro-inflammatory state in children with MIS-C
This is a 6 patient multisite pilot study to test whether infusions of hCT-MSC are safe in pediatric patients with MIS-C Information will also be gathered about the duration and severity of the participants multisystem inflammatory syndrome hCT-MSCs will be manufactured at Duke University Medical Center in the Robertson GMP Cell Manufacturing Laboratory and shipped frozen to the treatment site where they will remain stored in the vapor phase of liquid nitrogen until the day of dosing
The baseline evaluation will include vital signs heart rate blood pressure temperature respiratory rate echocardiogram ECG or telemetry strip HLA typing Panel Reactive Antibody anti-HLA antibody inflammatory markers blood counts blood chemistry coagulation and COVID-19 PCR and antibody testsPatients will be dosed with 2x106 hCT-MSCskg Doses will be given on days 1 2 3 and a fourth optional dose may be given on day 7 at the discretion of the investigator and the treating physician Prior to the infusion premedications Benadryl Hydrocortisone 05mgkg each will be administered The hCT-MSCs will be administered intravenously over 30-60 minutes via a syringe pump Pulse oximetry will be monitored continuously throughout the infusion and IV fluids will be managed by the care team Afterwards the participant will continue to be monitored in their care setting per institutional standards Participants will be evaluated by study staff the day after the infusion to assess for any infusion-related adverse reactions or complications
The participant will be monitored by study staff to assess for any infusion related adverse reactions or complications until discharge Additional follow-up will occur on days 14 28 and 90 Follow up testing will include assessment for adverse events as well as the tests done at baseline with the exception of HLA typing and COVID PCR
The study population will consist of six patients 18 to 21 years old with a life expectancy 72 hours and COVID-19 related MIS-C that is refractory to treatment with intravenous immune globulin IVIG
Multisystem inflammatory syndrome in children MIS-C is a newly recognized serious hyper-inflammatory syndrome that is occurring in small numbers of children many of whom are within a month or so of recovering from a COVID-19 infection While the clinical presentation varies affected patients are typically previously healthy individuals who are less than 21 years of age The diagnostic criteria include fever laboratory evidence of inflammation and multisystem involvement requiring hospitalization Up to 75 of patients present with an element of cardiogenic shock requiring inotropic support with some also requiring intubation with mechanical ventilation Reported supportive treatments have included intravenous immune globulin IVIG tocilizumab methylprednisolone and aspirin In the limited cases reported up to 50 of children with MIS-C have antibodies to COVID-19 in their blood and may or may not be PCR positive on a nasal swab or throat culture The disease is incompletely understood but currently believed at least in part to be a hyper-immune response to a recent COVID-19 infection
In laboratory experiments MSCs have been shown to inhibit T-cell proliferation and decrease production of pro-inflammatory cytokines In animal models up to 70 of infused cells are engulfed by lung macrophages leading to secretion of anti-inflammatory molecules by these macrophages These observations have led to the hypothesis that MSCs may work through both anti-inflammatory immune-modulatory and regenerative mechanisms
Over the past several months MSCs have been tested in small cohorts of adult patients with COVID-19 Acute Respiratory Distress Syndrome to determine if the cytokine storm hypothesized to cause this complication could be suppressed by MSCs Early results are encouraging and formal clinical trials are underway Extending this work into the pediatric population the hypothesis of this study is that infusion of hCT-MSC can reverse the pro-inflammatory state in children with MIS-C
This is a 6 patient multisite pilot study to test whether infusions of hCT-MSC are safe in pediatric patients with MIS-C Information will also be gathered about the duration and severity of the participants multisystem inflammatory syndrome hCT-MSCs will be manufactured at Duke University Medical Center in the Robertson GMP Cell Manufacturing Laboratory and shipped frozen to the treatment site where they will remain stored in the vapor phase of liquid nitrogen until the day of dosing
The baseline evaluation will include vital signs heart rate blood pressure temperature respiratory rate echocardiogram ECG or telemetry strip HLA typing Panel Reactive Antibody anti-HLA antibody inflammatory markers blood counts blood chemistry coagulation and COVID-19 PCR and antibody testsPatients will be dosed with 2x106 hCT-MSCskg Doses will be given on days 1 2 3 and a fourth optional dose may be given on day 7 at the discretion of the investigator and the treating physician Prior to the infusion premedications Benadryl Hydrocortisone 05mgkg each will be administered The hCT-MSCs will be administered intravenously over 30-60 minutes via a syringe pump Pulse oximetry will be monitored continuously throughout the infusion and IV fluids will be managed by the care team Afterwards the participant will continue to be monitored in their care setting per institutional standards Participants will be evaluated by study staff the day after the infusion to assess for any infusion-related adverse reactions or complications
The participant will be monitored by study staff to assess for any infusion related adverse reactions or complications until discharge Additional follow-up will occur on days 14 28 and 90 Follow up testing will include assessment for adverse events as well as the tests done at baseline with the exception of HLA typing and COVID PCR
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None