Infusions of Mesenchymal Stromal Cells in Children With Multisystem Inflammatory Syndrome

NCT04549285 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00106044
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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) and/or steroids will be given intravenous infusions of hCT-MSCs. Doses of 2x10\^6 cells/kg (up to a maximum dose of 100x10\^6 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 (i.e., vital signs, physical examinations), laboratory tests (i.e., hematology, serum chemistries, and urinalysis), and cardiac function (i.e., echocardiogram, ECG) from the signing of informed consent and throughout the patient's participation in this treatment protocol.

Conditions

Multisystem Inflammatory Syndrome in Children

Outcome Measures

Primary Outcomes (3)

• Safety of the Investigational Product, hCT-MSCs, infusion reactions

  Incidence of infusion reactions

  2 days post infusion

• Safety of the Investigational Product, hCT-MSCs, related adverse events

  Incidence of later reactions attributed to the investigational product

  90 days post initial infusion

• Safety of the Investigational Product, hCT-MSCs, anti-HLA antibodies

  Incidence of formation of new anti-HLA antibodies post infusion as compared to pre-infusion levels.

  from first dose of MSCs to 28 days after first dose

Secondary Outcomes (5)

• Survival

  from first dose of MSCs to 28 days after first dose

• Inotrope support

  from first dose of MSCs to 90 days after first dose

• Hospital Discharge

  from first dose of MSCs to 90 days after first dose

• Duration of ICU stay

  from first dose of MSCs to 90 days after first dose

• cardiac abnormalities

  from first dose of MSCs to 28 days after first dose

Study Arms (1)

hCT-MSC infusion

EXPERIMENTAL

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.

Biological: Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs)

Interventions

Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs) BIOLOGICAL

Human Umbilical Cord Tissue-derived Mesenchymal Stromal Cells (hCT-MSC): hCT-MSCs is an allogeneic cell product manufactured from donated umbilical cord tissue that is digested and expanded in culture, cryopreserved and banked. Doses contain 2x10\^6 cells/kg (up to a maximum dose of 100x10\^6 cells) diluted in plasmalyte-A with 5% HSA to a volume of 20-40mL.

hCT-MSC infusion

Eligibility Criteria

• Age: 18 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 to \<21 years
• Diagnosis: must meet ALL below criteria for COVID-19 related MIS-C as defined by the CDC.
• Age \<21 years
• No alternative plausible diagnoses
• Positive for current or recent SARS-CoV-2 infection or COVID-19 exposure within the 4 weeks prior to the onset of symptoms. Exposure may be measure by RT-PCR, Serology, Antigen test, or History.
• ALL of the following clinical symptoms:
• Fever ≥38.0 degrees C for ≥24 hours or report of subjective fever lasting
• hours
• Laboratory evidence of inflammation, including, but not limited to, one or more of the following: an elevated CRP, ESR, fibrinogen, procalcitonin, d- dimer, ferritin, LDH, or IL-6; elevated neutrophils, reduced lymphocytes, low albumin
• Clinically severe disease that requires hospitalization
• Multisystem (≥2) organ involvement:
• I. Cardiovascular involvement (ANY of the listed criteria):
• Cardiac dysrhythmia or arrythmia (NOTE: patients with prolonged QT interval or unstable dys/arrythmias are not eligible)
• Ejection fraction 35%-\<55%
• Pulmonary edema due to left heart failure

You may not qualify if:

• Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy, HIV, previous treatment for cancer, etc.)
• History of cancer
• History of previous treatments with MSCs or other cell therapies
• Patient is enrolled in any other IND-sponsored clinical trials for COVID-19
• Evidence of pregnancy or lactation
• Moribund patient not expected to survive \> 24 hours
• Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)
• Patient received CPR for this condition
• Patients who have acquired thrombotic risk due to COVID, e.g., VTE, pulmonary embolism, stroke, intracranial hemorrhage, ischemia of an extremity, or prone to thrombotic conditions, e.g., Factor V Leiden mutations, lupus anti-coagulant, etc.
• Patients with history of DMSO allergies
• unstable supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation)
• Chest tube
• Concurrent dialysis
• Suspected CNS infection
• Severe bronchospasm requiring continuous bronchodilators

Sponsors & Collaborators

• Joanne Kurtzberg, MD: lead

Study Sites (3)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

New York Medical College, Westchester Medical Center (WMC)

Westchester, New York, 10595, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

pediatric multisystem inflammatory disease, COVID-19 related

Study Officials

• Joanne Kurtzberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Jerome Harris Distinguished Professor of Pediatrics, Professor of Pathology; Director, Marcus Center for Cellular Cures; Director, Pediatric Blood and Marrow Transplant Program;

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: March 12, 2021
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: September 14, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)