Cord Blood-Derived Mesenchymal Stem Cells for the Treatment of COVID-19 Related Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Study of Cord Blood Derived Mesenchymal Stem Cells for Treatment Acute Respiratory Distress Syndrome

Conditions
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COVID-19 Infection, COVID-19-Associated Acute Respiratory Distress Syndrome, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Symptomatic COVID-19 Infection Laboratory-Confirmed

Intervention / Treatment
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* Other: Best Practice
* Biological: Mesenchymal Stem Cell


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase II Arm I (mesenchymal stem cells)<br>Patients receive MSCs as in the Pilot study. | Biological: Mesenchymal Stem Cell<br>* Given IV<br>* Other names: MPC;|
| Active Comparator: Phase II Arm II (standard of care)<br>Patients receive standard of care. | Other: Best Practice<br>* Receive standard of care<br>* Other names: standard therapy;|
| Experimental: Pilot study (mesenchymal stem cells)<br>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. | Biological: Mesenchymal Stem Cell<br>* Given IV<br>* Other names: MPC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite serious adverse events (Phase I) | Serious adverse events with be comprised of grade 3 or 4 graft versus host disease or death and will be estimated and reported overall and by group, along with 95% confidence intervals. | Within 30 days of the first mesenchymal stem cell (MSC) infusion | 
| Patients alive without grade 3, 4 infusional toxicity (Phase II) |  | At day 30 post MSC infusion | 
| Patients alive with grade 3 or 4 infusional toxicity (Phase II) |  | At day 30 post MSC infusion | 
| Patients not alive (Phase II) |  | At day 30 post MSC infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of successfully extubated patients who present intubated on ventilator support (Phase I) | Will be estimated and reported with 95% confidence intervals. | Up to day 30 post MSC infusion | 
| Rate of successful progression to intubation in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Phase I) | Will be estimated and reported with 95% confidence intervals. | Up to day 30 post MSC infusion | 
| Overall survival rate (Phase I) | Will be estimated and reported with 95% confidence intervals. | At day 30 post MSC infusion | 
| Survival rate in patients who present intubated on ventilator support (Phase I) | Will be estimated and reported with 95% confidence intervals. | At day 30 post MSC infusion | 
| Survival rate in patients who require supplemental oxygen but who are otherwise able to breathe without assistance (Phase I) | Will be estimated and reported with 95% confidence intervals. | At day 30 post MSC infusion | 
| Clinical parameters (Phase I) | The effect of MSCs on clinical parameters will be assessed. Continuous clinical parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables. | Up to day 30 post MSC infusion | 
| Oxygenation parameters (Phase I) | The effect of MSCs on oxygenation parameters will be assessed. Continuous oxygenation parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables. | Up to day 30 post MSC infusion | 
| Respiratory parameters (Phase I) | The effect of MSCs on respiratory parameters will be assessed. Continuous respiratory parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables. | Up to day 30 post MSC infusion | 
| Laboratory markers (Phase I) | The effect of MSCs on laboratory markers will be assessed. Continuous laboratory parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables. | Up to day 30 post MSC infusion | 
| Hospitalization stay (Phase I) |  | Up to day 30 post MSC infusion | 
| Intensive care unit stay (Phase I) |  | Up to day 30 post MSC infusion | 
| Incidence of infusion-related adverse events (Phase I) | All grades of infusion-related adverse events will be summarized by grade and type. | Up to day 30 post MSC infusion |