Overview
This is a phase I trial followed by a phase II randomized trial. The purpose of phase I study is the feasibility of treating patients with acute respiratory distress syndrome (ARDS) related to COVID-19 infection (COVID-19) with cord blood-derived mesenchymal stem cells (MSC). The purpose of the phase II trial is to compare the effect of MSC with standard of care in these patients. MSCs are a type of stem cells that can be taken from umbilical cord blood and grown into many different cell types that can be used to treat cancer and other diseases. The MSCs being used for infusion in this trial are collected from healthy, unrelated donors and are stored and grown in a laboratory. Giving MSC infusions may help control the symptoms of COVID-19 related ARDS.
Description
PRIMARY OBJECTIVE:
I. To assess the safety of administering cord blood derived mesenchymal stem cell (CB-MSC) infusions for treatment of COVID-19 acute respiratory distress syndrome (ARDS).
SECONDARY OBJECTIVES:
I. In the group of patients who present intubated on ventilator support, assess the proportion that are able to be successfully extubated.
II. In the group of patients who present requiring supplemental oxygen but otherwise breathing without assistance, assess the rate of progression to intubation.
III. Estimate the survival rate at day 30 post treatment separately by group.
IV. Determine the treatment effect on clinical parameters, oxygenation and respiratory
- parameters
IVa. Resolution of fever. IVb. Changes in oxygen demand (increased oxygen saturation at similar fraction of inspired oxygen [FiO2] or decreased FiO2 requirement).
IVc. Progression to mechanical ventilation. IVd. Length of mechanical ventilation. IVe. Decrease in positive end-expiratory pressure (PEEP) in intubated patients. IVf. Decrease in FiO2 in intubated patients.
V. Determine the treatment effect on laboratory markers:
Va. Complete blood count. Vb. C-reactive protein (CRP). Vc. Ferritin. Vd. D dimer. Ve. Procalcitonin. Vf. Cytokine levels. VI. Estimate hospitalization and intensive care unit (ICU) stay. VII. Report on study related adverse events.
- OUTLINE
Currently not shipping cells outside of MD Anderson Cancer Center in Houston.
PILOT STUDY: Patients receive MSCs intravenously (IV) over 1-2 hours on day 1. Patients may receive a second infusion of MSCs within 7 days after the first infusion per physician discretion.
PHASE II STUDY: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive MSCs IV over 1-2 hours on day 1. Patients may receive a second infusion of MSCs within 7 days after the first infusion per physician discretion.
ARM II: Patients receive standard of care.
After completion of study treatment, patients are followed up at days 7, 14, 30, 60, and months 6 and 12.
Eligibility
Inclusion Criteria:
- Patients with moderate to severe ARDS per Berlin criteria secondary to COVID-19. Moderate to severe is defined in appendix as the following: moderate partial pressure of arterial oxygen (PaO2)/FiO2 of 100-200 mm Hg, severe PaO2/FiO2 of less than 100 mm Hg
- Negative pregnancy test in a woman with childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
- Patient or legally authorized representative consent
- Because of the nature of COVID-19, patients enrolled on this study with COVID-19 associated ARDS may have been previously enrolled in other Investigational New Drug (IND) trials for their cancer diagnosis or COVID-19. These enrollments will not exclude them from enrollment to this study
Exclusion Criteria:
- Moribund patients not expected to survive up to 48 hours
- Patients with severe chronic liver disease (Childs-Pugh score > 10)
- Pregnant and/or lactating women
- Patients on extracorporeal membrane oxygenation