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Infusions of Mesenchymal Stromal Cells in Children With Multisystem Inflammatory Syndrome (MISTIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04549285
Recruitment Status : Not yet recruiting
First Posted : September 16, 2020
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

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.

Condition or disease Intervention/treatment Phase
Multisystem Inflammatory Syndrome in Children Biological: Human Cord Tissue Mesenchymal Stromal Cells (hCT-MSCs) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2021

Arm Intervention/treatment
Experimental: hCT-MSC infusion
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)

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.





Primary Outcome Measures :
  1. Safety of the Investigational Product, hCT-MSCs, infusion reactions [ Time Frame: 2 days post infusion ]
    Incidence of infusion reactions

  2. Safety of the Investigational Product, hCT-MSCs, related adverse events [ Time Frame: 90 days post initial infusion ]
    Incidence of later reactions attributed to the investigational product

  3. Safety of the Investigational Product, hCT-MSCs, anti-HLA antibodies [ Time Frame: from first dose of MSCs to 28 days after first dose ]
    Incidence of formation of new anti-HLA antibodies post infusion as compared to pre-infusion levels.


Secondary Outcome Measures :
  1. Survival [ Time Frame: from first dose of MSCs to 28 days after first dose ]
    Survival rate at 28 days after the first dose of MSCs

  2. Inotrope support [ Time Frame: from first dose of MSCs to 90 days after first dose ]
    Description of duration of inotrope support after the first dose of MSCs

  3. Hospital Discharge [ Time Frame: from first dose of MSCs to 90 days after first dose ]
    Description of number of days to hospital discharge to home

  4. Duration of ICU stay [ Time Frame: from first dose of MSCs to 90 days after first dose ]
    Description of Duration of ICU stay

  5. cardiac abnormalities [ Time Frame: from first dose of MSCs to 28 days after first dose ]
    Incidence of cardiac abnormalities at day 28, defined as persistent abnormalities in ECG, Echo, or biochemical markers (pro-BNP, troponin).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 20 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 18 to <21 years
  2. Diagnosis: must meet ALL below criteria for COVID-19 related MIS-C as defined by the CDC.

    1. Age <21 years
    2. No alternative plausible diagnoses
    3. 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.
    4. ALL of the following clinical symptoms:

      • Fever ≥38.0 degrees C for ≥24 hours or report of subjective fever lasting

        • 24 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
      • Pericarditis or pericardial effusion (not requiring drainage)
      • B-type natriuretic peptide (BNP) >400 pg/mL
      • Elevated troponin (based on the upper limit of normal for the laboratory running the assay)
      • Receipt of vasopressor or vasoactive support

      II. Respiratory Involvement (includes ANY of the listed criteria)

      • Receipt of mechanical ventilation or any type of supplemental oxygen (or increased support for patients receiving respiratory support at baseline)
      • Pulmonary infiltrates on chest radiograph
      • Lower respiratory infection
      • Pleural effusion (not requiring chest tube)
      • Pneumothorax (not requiring chest tube)

      III. Ophthalmologic involvement

      • Iritis or uveitis

      IV. Gastrointestinal involvement (includes ANY of the listed criteria)

      • Nausea/vomiting
      • Diarrhea
      • Abdominal pain
      • Pancreatitis (amylase and/or lipase >200 U/L or radiologic findings)
      • Hepatitis (AST and/or ALT >500 U/L)
      • Gallbladder hydrops or edema

      V. Hematologic involvement (includes ANY of the listed criteria)

      • Total white blood cell <4 x10^3/μL
      • Anemia (hemoglobin <9 g/dL)
      • Platelet count <150,000 /μL
      • Hemolysis VI. Mucocutaneous involvement (includes ANY of the listed criteria)
      • Bilateral conjunctival injection
      • Oral mucosal changes
      • Peripheral extremity changes
      • Rash or skin ulcers
      • 'COVID' toes
      • Swollen red cracked lips
      • Erythema of palms or soles
      • Edema of hands or feet
      • Periungual (nails) desquamation
      • Conjunctivitis
      • Peripheral gangrene

      VII. Musculoskeletal involvement (includes ANY of the listed criteria)

      • Arthritis or arthralgia involvement
      • Myositis or myalgia
  3. Prior therapy: must have been treated with IVIG (maximum cumulative dose of 5g/kg) 1-7 days prior to enrollment. Patients will be eligible if they have progressive symptoms ≥24 hours after initiation of IVIG or lack of response ≥48 hours after initiation of IVIG. Lack of response is defined as inability wean off of supportive care measures (ie. vasopressors, mechanical ventilation, oxygen support) or lack of improvement in inflammatory markers.
  4. Prior treatment with immunomodulators (e.g. tocilizumab, etc) is allowed if there was no response or progressive disease 2 days (48 hours) or more after initiation of this therapy.
  5. Life expectancy ≥ 72 hours
  6. Legal authorized representative consent

Exclusion Criteria:

  1. Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy, HIV, previous treatment for cancer, etc.)
  2. History of cancer
  3. History of previous treatments with MSCs or other cell therapies
  4. Patient is enrolled in any other IND-sponsored clinical trials for COVID-19
  5. Evidence of pregnancy or lactation
  6. Moribund patient not expected to survive > 24 hours
  7. Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)
  8. Patient received CPR for this condition
  9. 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.
  10. Patients with history of DMSO allergies
  11. ECG exclusions: prolonged QT interval, changes suggestive of myocardial ischemia, unstable cardiac dys/arrythmia that requires medical stabilization (ie.

    unstable supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation)

  12. Echocardiogram exclusions: Dilated coronary artery(ies) (z score >2), aneurysms, ectasia, pericardial effusion requiring drainage, or focal wall abnormalities suggestive of myocardial ischemia
  13. Chest tube
  14. Concurrent dialysis
  15. Suspected CNS infection
  16. Severe bronchospasm requiring continuous bronchodilators
  17. Pulmonary hemorrhage
  18. A formal diagnosis of full Kawasaki disease (KD).
  19. Failure to perform COVID-19 PCR and serology testing prior to IVIG administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04549285


Contacts
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Contact: Jessica Sun, MD 919-684-3401 jessica.sun@duke.edu
Contact: Jennifer Baker, RN (919) 668-6536 jennifer.hungate@duke.edu

Locations
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United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
Contact: Edwin Horwitz, MD, PhD    404-727-1958    edwin.horwitz@emory.edu   
United States, New York
New York Medical College, Westchester Medical Center (WMC)
Westchester, New York, United States, 10595
Contact: Mitchell S. Cairo, MD    914-594-2150      
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Joanne Kurtzberg, MD
Investigators
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Principal Investigator: Joanne Kurtzberg, MD Duke University
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Responsible Party: Joanne Kurtzberg, MD, Jerome Harris Distinguished Professor of Pediatrics, Professor of Pathology; Director, Marcus Center for Cellular Cures; Director, Pediatric Blood and Marrow Transplant Program;, Duke University
ClinicalTrials.gov Identifier: NCT04549285    
Other Study ID Numbers: Pro00106044
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: September 22, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes