Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 Induced ARDS: A Non-Blinded Randomized, Controlled Study
Phase: PHASE1
Conditions: Sars-CoV2, Acute Respiratory Distress Syndrome, COVID-19
Sponsor: Baylor College of Medicine

MSC for COVID-19 Version 1.0 (04-03-2020)                     Version 2.2 (11-05-2020)                     Version 4.1 (08-31-2021) 
                Version 2.0 (05-21-2020)                     Version 3.0 (02-23-2021)                     Version 4.2 (05-25-2022) 
                                
                Version 2.1 (10-21-2020) 
 Version 4.0 (04-13-2021)                      
Protocol Title:  
Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 
Induced ARDS: A Non-Blinded Randomized, Controlled Study 
 
Principal Investigators:  
LaQuisa Hill, MD 
Adrian Gee, PhD 
Zhuyoung Mei, MD 
 
Co-Investigators:  
Helen Heslop, MB, ChB, MD, DSC (Hon), FRACP, FRCPA 
George Carrum, MD 
Rammurti Kamble, MD 
Premal Lulla, MBBS 
Carlos Ramos, MD 
Sai Pingali, MD 
Jenny Chang, MD 
Bambi Grilley, RPh 
 
Statistician 
Tao Wang, PhD 
 
IND # 21643 
 
Center for Cell and Gene Therapy 
 
Houston Methodist Hospital 
6565 Fannin Street 
Houston, TX  77030-2707 
 
Dan L. Duncan Comprehensive Cancer Center 
Baylor College of Medicine 
 
 
 
 
 
 
 
 

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Table of Contents 
1 
Background and Rationale ....................................................................................................... 7 
1.1 
Acute Respiratory Distress Syndrome (ARDS).................................................................. 7 
1.2 
Coronavirus Disease 2019 (COVID-19) ............................................................................. 7 
1.3 
ARDS due to COVID-19 Disease ........................................................................................ 8 
1.4 
COVID-19-associated coagulopathy (CAC) ....................................................................... 8 
1.5 
Mesenchymal Stromal Cells (MSCs) for Inflammatory Disorders, including ARDS ......... 9 
1.6 
Procoagulant effects of MSCs ........................................................................................ 10 
2 
Study Design .......................................................................................................................... 10 
2.1 
Study Overview .............................................................................................................. 10 
2.2 
Hypothesis and Specific Objectives ................................................................................ 10 
2.2.1 
Primary Hypothesis ................................................................................................. 10 
2.3 
Study Objective. ............................................................................................................. 11 
2.3.1 
Primary endpoints:.................................................................................................. 11 
2.3.2 
Secondary endpoints: ............................................................................................. 11 
2.3.3 
Exploratory endpoints............................................................................................. 11 
3 
Eligibility Criteria ................................................................................................................... 11 
3.1 
Inclusion Criteria ............................................................................................................ 11 
3.2 
Exclusion Criteria ............................................................................................................ 12 
4 
Mesenchymal Stromal Cells (MSCs) Manufacturing ............................................................ 12 
4.1 
Source Material. ............................................................................................................. 12 
4.2 
Ex vivo cell expansion. .................................................................................................... 13 
4.3 
Freezing. ......................................................................................................................... 13 
4.4 
Testing. ........................................................................................................................... 14 
5 
Patient Enrollment and Evaluation ....................................................................................... 14 
5.1 
Informed Consent .......................................................................................................... 14 
5.2 
Registration and Randomization .................................................................................... 14 
5.3 
Treatment Plan ............................................................................................................... 14 
5.3.1 
Dosing ..................................................................................................................... 14 
5.3.2 
Administration and Monitoring of MSC Infusion ................................................... 15 
5.3.3 
Supportive Care for the control arm....................................................................... 15 
6 
Patient Evaluation ................................................................................................................. 16 

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6.1 
Study Calendar ............................................................................................................... 16 
7 
Evaluations ............................................................................................................................ 18 
7.1 
Baseline Pre-treatment Evaluation ................................................................................ 18 
7.2 
Post-randomization/treatment Evaluation .................................................................... 18 
7.3 
Follow up ........................................................................................................................ 19 
7.4 
Drug Toxicity and/or Adverse Reactions ........................................................................ 19 
8 
Statistical Considerations ...................................................................................................... 20 
8.1 
Clinical Trial Design......................................................................................................... 20 
8.2 
Sample size ..................................................................................................................... 20 
8.3 
Randomization and Stratification .................................................................................. 21 
8.4 
Safety monitoring and stopping rule ............................................................................. 21 
8.5 
Statistical Analysis .......................................................................................................... 21 
9 
Off Treatment and Off Study Criteria ................................................................................... 22 
9.1 
Off Treatment Criteria .................................................................................................... 22 
9.2 
Off Study Criteria ............................................................................................................ 23 
10 Clinical Trial Oversight and Monitoring ................................................................................ 23 
 
 

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CHECKLIST FOR PATIENT ELIGIBILITY FOR TREATMENT  
 
 
YES 
NO 
VALUE/DATE 
 
Any “NO” answers will make a patient ineligible for study participation.  
 
 
 
18 years or older 
 
 
 
Confirmed SARS-CoV2 infection real-time reverse transcription 
polymerase chain reaction (RT-PCR) assay 
 
 
 
Moderate OR severe acute respiratory distress syndrome 
(ARDS), based on the degree of impairment of oxygenation as 
defined by the ratio of arterial oxygen tension to fraction of 
inspired oxygen (PaO2/FiO2):  
a. Moderate ARDS: PaO2/FiO2 100-200 mmHg  
OR 
b. Severe ARDS: PaO2/FiO2 ≤100 mmHg 
 
 
 
 
If on invasive or non-invasive (BiPAP) mechanical 
ventilator,PEEP ≥5 cm H2O 
 
 
 
Bilateral opacities present on chest radiograph or computed 
tomographic (CT) scan, that are not fully explained by pleural 
effusions, lung collapse, or lung nodules. 
YES 
NO 
VALUE/DATE 
 
Any “YES” answers will make a patient ineligible for study participation.  
 
 
 
Currently receiving extracorporeal membrane oxygenation 
(ECMO) 
 
 
 
Severe chronic respiratory disease requiring current use of 
home oxygen prior to COVID-19 diagnosis 
 
 
 
Pregnant or lactating 
 
 
 
Known hypersensitivity to dimethyl sulfoxide (DMSO) 
 
 
 
Unstable hemodynamics as deemed by the treating 
physician/investigator including but not limited to unstable , 
ventricular tachycardia or new cardiac arrythmia requiring 
cardioversion 
 
 
 
Uncontrolled bacterial or fungal co-infection 
 
 
 
Any end-stage organ disease or condition, which in the opinion 
of the Investigator, makes the patient an unsuitable candidate 
for treatment 
 
 
 
Inability to obtain informed consent (from patient or legally 
appropriate proxy) 
 
 
 
Presence of any contraindication to receiving prophylactic low 
dose unfractionated or low molecular weight heparin 
 
 
 
Respiratory failure explained or complicated by cardiac failure 
or fluid overload 
 
Signature of MD ______________________ Date ____________________ 
 
 

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PROTOCOL SYNOPSIS 
Single Donor Banked Bone Marrow Mesenchymal Stromal Cells for the Treatment of COVID-19 
Induced ARDS: A Non-Blinded Randomized Controlled Study 
 
 
Principal Investigator: 
LaQuisa Hill, MD 
 
Study Design:  
 
Single center, open-label, non-blinded randomized controlled 
study 
 
Objective: 
 
To evaluate the safety and clinical benefits of banked   
mesenchymal stromal cells (MSCs) versus controls for treatment    
of patients with ARDS due to COVID-19 
 
Eligibility Criteria: 
 
 
                                 
 
Inclusion Criteria 
1) 18 years or older 
2) Confirmed SARS-CoV2 infection real-time reverse transcription 
polymerase chain reaction (RT-PCR) assay 
3) Moderate OR severe acute respiratory distress syndrome 
(ARDS), based on the degree of impairment of oxygenation as 
defined by the ratio of arterial oxygen tension to fraction of 
inspired oxygen (PaO2/FiO2):    
a. Moderate ARDS:  PaO2/FiO2 100-200 mmHg  
OR 
b. Severe ARDS: PaO2/FiO2  ≤100 mmHg  
4) If on invasive or non-invasive (BiPAP) mechanical ventilator 
PEEP ≥5 cm H2O 
5) Bilateral opacities present on chest radiograph or computed                       
                                                                tomographic (CT) scan, that are not fully explained by   
                                                                pleural effusions, lung collapse, or lung nodules. 
 
 
 
 
 
Exclusion Criteria 
1) Currently receiving extracorporeal membrane oxygenation 
(ECMO)  
2) Severe chronic respiratory disease requiring current use of 
home oxygen prior to COVID-19 diagnosis 
3) Pregnant or lactating  
4) Known hypersensitivity to dimethyl sulfoxide (DMSO)  
5) Unstable hemodynamics as deemed by the treating 
physician/investigator including but not limited to unstable , 
ventricular  tachycardia or new cardiac arrythmia requiring 
cardioversion 

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6) Uncontrolled bacterial or fungal co-infection 
7) Any end-stage organ disease or condition, which in the 
opinion of the Investigator, makes the patient an unsuitable 
candidate for treatment 
8) Inability to obtain informed consent (from patient or legally 
appropriate proxy) 
9) Presence of any contraindication to receiving prophylactic low 
dose unfractionated or low molecular weight heparin  
10) Respiratory failure not fully explained by cardiac failure or 
fluid overload.        
 
 
 

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1 
Background and Rationale 
1.1 
Acute Respiratory Distress Syndrome (ARDS) 
  Acute respiratory distress syndrome (ARDS) is an acute, life-threatening form of    
  respiratory failure caused by diffuse inflammatory mediated alveolar injury leading to    
  impaired gas-exchange, decreased compliance and fluid accumulation in the airspaces.  
  Excessive inflammation is a major contributor to lung injury in ARDS leading to   
  activation of the complement system by alveolar macrophages and the   
  release of pro-inflammatory cytokines such as TNF, IL-1, IL-6, and IL-17, as well as  
               multiple chemokines such as IL-8, CCL-2, and CCL-7 [1]. This leads to the accumulation  
  of neutrophils and monocytes to the site of injury where they release toxic substances   
  that damage the capillary endothelium and alveolar epithelium [1]. The ensuing   
  cytokine storm leads to systemic inflammatory response, septic shock, and multi-organ   
  failure [2, 3].  Multiple etiologies may trigger ARDS, including respiratory infections,   
  sepsis/shock, trauma, pancreatitis, smoke inhalation, hematopoietic stem cell   
  transplant, and transfusion-related acute lung injury.   
 
  ARDS is currently diagnosed based on the Berlin Definition of ARDS published in   
  2012 based on expert consensus [4].  It is clinically manifested by dyspnea and poor   
  arterial oxygenation which is determined by the ratio of arterial partial pressure of  
  oxygen to fraction of inspired oxygen (PaO2/FIO2), along with bilateral opacities on  
  chest imaging.  ARDS is divided into 3 groups based on the degree of hypoxemia: mild  
  (PaO2/FIO2 201-300 mm Hg), moderate (PaO2/FIO2: 101-200 mm Hg), and severe  
  (PaO2/FIO2 ≤ 100 mm Hg) and ventilator settings with a positive end-expiratory  
  pressure (PEEP) or continuous positive airway pressure (CPAP) ≥5 cm H2O.  The  
  mortality rate has been reported to be up to 50%, with increasing severity of ARDS   
  leading to higher likelihood of mortality [5]. To date, no pharmacologic therapies have    
  shown any benefit in reducing the high mortality of ARDS, and the primary treatment   
  relies on treating underlying causes and supportive measures such as mechanical  
  ventilation and fluid management [1].  Thus, effective therapies are  
  needed.  
1.2 
Coronavirus Disease 2019 (COVID-19) 
 Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome   
 coronavirus 2 (SARS-CoV-2), and was first reported in Wuhan, China in December 2019    
[6] . In January 2020, the World Health Organization (WHO) declared the outbreak a   
 global emergency after rapid spread to multiple other countries including the United    
 States, Italy, Japan, Iran and others. The number of cases continues to increase  
exponentially with the number of cases surpassing 1,500,000 globally by April 10, 2020 
[7].  
 
SARS-CoV2 belongs to the Coronavirus (CoV) family which also includes the severe   
acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory   

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syndrome coronavirus (MERS-CoV) which led to epidemics 2003 and 2012, respectively.  
While COVID-19 shares a similar clinical presentation with SARS-CoV, it appears to have 
a higher transmission rate although the estimated basic reproductive number (R0) has 
been very dynamic as the number of cases continues to rise with increased testing 
availability  [8-11].  The most common clinical symptoms of COVID-19 at onset are fever, 
cough, dyspnea, myalgia, and/or fatigue [10, 12, 13]. Less common symptoms included 
anosmia, headache, diarrhea, nausea, and vomiting.  However, the clinical spectrum 
ranges widely from asymptomatic or mild illness to critical illness in a subset of patients 
with progression to ARDS, shock, and/or multi-organ failure leading to a case fatality 
rate variously estimated as 1%-4%.  [14].  
 
1.3 
 ARDS due to COVID-19 Disease 
Angiotensin converting enzyme-2 receptor (ACE-2) has been identified as a primary   
host receptor for cell entry utilized by SARS-CoV-2 similar to SARS-CoV [15, 16]. ACE-2 is 
highly expressed in multiple organs including but not limited to the oral cavity, human 
airway epithelia, myocardial cells, and kidney proximal tubule cells, and high expression 
may increase susceptibility to viral damage. It has been reported that approximately 
50% of patients with COVID-19 pneumonia will progress to ARDS [12, 13, 17], with 
mortality approaching 50% in various studies [10, 12, 13, 17, 18]. Risk factors for ARDS 
and increased mortality include age (older than 60 years), presence of comorbidities 
such as hypertension, diabetes, heart disease, COPD, immunocompromised states, 
elevated markers of inflammation and higher disease severity as evidenced by high 
APACHE II, SOFA, and CURB-65 scores [10, 18-21].  At present, no effective antiviral 
treatment or vaccine is available; however, multiple clinical trials are evaluating the 
safety and efficacy of pharmacologic agents.   
 
1.4 
  COVID-19-associated coagulopathy (CAC) 
Abnormalities in coagulation parameters have been observed in patients hospitalized    
with COVID-19 disease [12, 19, 22, 23].  Most common are elevations in fibrinogen and 
D-dimer, which may correlate with a rise in inflammatory markers. However, some 
patients with severe COVID-19 disease develop classic disseminated intravascular 
coagulopathy (DIC) with moderate to severe thrombocytopenia, prolongation of 
PT/aPTT, elevated D-dimer, and fibrinogen less than 100 mg/dL.  Tang et al reported 
that use of low molecular weight (LMWH) or unfractionated (UFH) heparin  was 
associated with decreased mortality in patients with severe COVID-19 disease [24]. 
Conversely, progressively increasing D-dimer levels were associated with increased 
mortality.  Based on these (and related) findings, monitoring of platelet counts, 
PT/aPTT, D-dimer and fibrinogen levels is strongly recommended.  While the use of 
therapeutic anticoagulation in patients with severe COVID-19 disease is still under study, 
prophylactic low dose heparin anticoagulation is recommended in the absence of active 
bleeding or other contraindications.  
 

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1.5 
 Mesenchymal Stromal Cells (MSCs) for Inflammatory Disorders, including ARDS 
 Mesenchymal stromal cells have shown benefit in patients with inflammatory and 
immune-related disorders, such as inflammatory bowel disease [25], rheumatoid 
arthritis [26], type 1 diabetes mellitus [27-29], systemic lupus erythematosus [30-33], 
multiple sclerosis [34], and acute graft versus host disease (aGVHD) [35] as well as lung 
disease [36-38]. MSCs are a cellular component of the supportive microenvironment 
that function as multipotent progenitor cells with the capacity to differentiate into 
mesodermal lineages, such as adipocytes, osteocytes, and chondrocytes [39, 40]. MSCs 
also contribute to tissue repair [41-43]. They also have anti-inflammatory properties and 
increase the activity of T regulatory cells, which may benefit development of immune 
tolerance [44-47].  Since MSCs do not express class II human histocompatibility antigens 
(HLA) or co-stimulatory molecules  (CD40, CD40L, CD80, and CD86) required for T cell 
activation, even allogeneic (banked) MSC appear to induce little alloreactivity after 
administration [48, 49]. MSCs also secrete antimicrobial peptides that enhance bacterial 
clearance and improve survival [50-52]. These inherent qualities of MSCs make them a 
promising candidate for the treatment of lung injury without toxicities.  
 
Multiple preclinical studies have shown that MSCs can be used for treating lung injury 
[53-55]. Chan et al showed that human MSCs administered to aged mice infected with 
H5N1 prevented or reduced lung injury, thereby increasing oxygenation. The MSCs 
reduced pro-inflammatory cytokines and increased survival [56]. MSC administration 
similarly reduced proinflammatory cytokines and chemokines, and pulmonary 
inflammation in mice with H9N2 avian influenza induced lung injury [57].  MSCs also 
attenuate lung injury in mice and ex vivo human lungs after injury by live bacterial 
infections [51, 58]. In addition, MSCs may secrete paracrine factors that improve the 
rate of alveolar fluid clearance [59, 60]. Based on these preclinical findings, MSCs were 
deemed to be a promising form of adoptive cell therapy for the treatment of ARDS. 
 
Several phase 1 and 2 studies evaluating the safety of MSCs as treatment for a variety of 
lung diseases (idiopathic pulmonary fibrosis, COPD and ARDS) have confirmed 
tolerability of this approach [36-38, 61, 62].  A case report of two patients with severe, 
refractory ARDS treated with MSC from  allogeneic bone marrow (2 million cells/kg i.v.) 
had  significant improvement of respiratory and end-organ failure, as well as reduction 
in inflammatory cytokines [63].  In a phase 1, dose-escalation study using bone marrow 
derived allogeneic MCSs for moderate to severe ARDS, no infusion or treatment related 
adverse events were reported in 9 recipients [62]. Two patients died, but this was 
considered unrelated to infusion of the MSCs.  Given the mortality associated with 
COVID-19 induced ARDS, Leng et al. conducted a pilot study of MSC administration in 
patients with confirmed SARS-CoV-2 pneumonia. They reported improvement in 
pulmonary function and symptoms, and a decrease in pro-inflammatory cytokines such 
as TNF-α and an increase in anti-inflammatory IL-10 [21]. They were also able to show 
improvement, although not statistically significant, in the disease severity scores such as 
SOFA.   

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1.6 
   Procoagulant effects of MSCs 
Although MSCs have been safely used in numerous clinical trials, preparations of these 
cells may express Tissue Factor and therefore pose an increased thrombogenic risk [64-
67].  Thus the general safety of bone marrow derived MSCs [68] has been accompanied 
by reports of thrombotic and embolic complications in animal and human studies when 
the MSCs were derived from alternative sources such as adipose tissue or placental 
tissue [65, 69-73]. MSC from these sources may express higher levels of TF [74, 75] 
than BM derived MSCs, potentially accounting for the observed “instant blood-
mediated inflammatory reactions” (IBMIR) [76, 77].   
 
The TF expression of adipose and placenta derived MSC shows significant variation 
depending on donor and culture passage [66, 70, 78, 79]. Although these thrombotic 
complications are rarely seen after infusion of BM derived MSCs, low dose 
anticoagulation has been used preclinically and in human studies [72, 74, 75, 80, 81].  
These additives block activation of coagulation and complement, decreasing the risk of 
IBIM-triggering. Thus, supplementation with anticoagulants appears to be a simple 
method to reduce activation of coagulation pathways following MSC infusion, which 
might also enhance the therapeutic effect. Thus in an effort to mitigate any putative 
additional procoagulation activity following infusion of MSCS, patients with active 
COVID 19 disease must be eligible for prophylaxis with LMWH/UFH. 
2 
Study Design 
2.1 
  Study Overview 
              This study is a single center open label, non-blinded randomized, controlled study 
designed to evaluate the use of single donor banked bone marrow derived MSCs versus 
standard of care as therapy   for patients with ARDS due to COVID-19 disease. The 
study will first enroll and treat six patients with MSCs for safety run in. If no more than 
2 treatment-related severe adverse events (tSAEs) are observed, the study will enroll 
and randomize additional 60 patients in a ratio of 1:1 to receive either MSCs or 
routine/supportive care.  
2.2 
    Hypothesis and Specific Objectives 
2.2.1  Primary Hypothesis 
               The primary hypothesis is that banked, bone marrow derived mesenchymal   
               stromal cells can be safely used to mediate the severe inflammatory response seen in 
               moderate or severe ARDS resulting from COVID-19 disease compared to the control  
               group receiving routine supportive care. 
 

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2.3 
   Study Objective:  
  To evaluate the safety and clinical benefits of banked mesenchymal stromal cells (MSCs) 
versus control for treatment of patients with COVID-19 induced ARDS. 
2.3.1   Primary endpoints: 
                        1.   Treatment-related serious adverse events (tSAEs) 
                        2.   Improvement by at least two categories on a six category ordinal scale at day  
 
 
    14 post randomization. The six-category ordinal scale is as follows:  
 
 
    6 ꞊ death; 5 ꞊ hospitalization, requiring extracorporeal membrane oxygenation 
 
 
    (ECMO) and/or invasive mechanical ventilation (IMV); 4 ꞊ hospitalization,       
                               requiring non-invasive mechanical ventilation (NIV) and/or                                          
                               High-flow nasal cannula (HFNC) therapy; 3 = hospitalization, requiring  
                               supplemental oxygen (but not NIV/HFNC); 2 = hospitalization, not requiring  
                               supplemental oxygen; 1 = hospital discharge.                                              
2.3.2 Secondary endpoints:  
 
           1.   Clinical status at day 28 as determined by 6-point ordinal scale 
                        2.   Severity of ARDS at day 14 
                        3.   Oxygenation free days at day 28  
  
           4.   Progression to mechanical ventilation or ECMO 
                        5.   Duration of mechanical ventilation and/or ECMO (ventilation/ECMO free days  
                               at day 28) 
                        6.   Duration of ICU stay (ICU free days at day 28) 
                        7.   Duration of hospital stay (time to discharge) 
                        8.   Overall survival 
                        9.      All-cause mortality at day 28                      
2.3.3 Exploratory endpoints 
 
           1.   Changes in inflammatory markers (CRP, IL-6, IL-10, TNF-α) 
                        2.   Negative SARS-CoV-2 RT-PCR by day 28 (if available) 
                        3.   Changes in blood safety laboratories (CBC with differential, electrolytes, renal  
                               indices, liver function studies, LDH, coagulation studies if available) 
                        4.   Corticosteroid use and duration 
                        5.   Changes in chest imaging             
                        6.   Evolution of other end-organ damage (hepatic, renal, cardiovascular)                                
                        7.   Changes in disease severity score (SOFA, CURB-65)      
                        8.   Duration of vasopressor use 
3 
Eligibility Criteria 
3.1 
Inclusion Criteria 
1) 18 years or older 

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2) Confirmed SARS-CoV2 infection real-time reverse transcription polymerase chain 
reaction (RT-PCR) assay 
3) Moderate OR severe ARDS, based on the degree of impairment of oxygenation as 
defined by the ratio of arterial oxygen tension to fraction of inspired oxygen 
(PaO2/FiO2): 
a. Moderate ARDS:  PaO2/FiO2 100-200 mmHg  
OR 
b. Severe ARDS: PaO2/FiO2  ≤100 mmHg  
4) If on invasive or noninvasive (BiPAP) mechanical ventilator, PEEP ≥5 cm H2O 
5) Bilateral opacities present on chest radiograph or computed tomographic (CT) 
scan, that are not fully explained by pleural effusions, lung collapse, or lung 
nodules. 
3.2 
    Exclusion Criteria 
1) Currently receiving extracorporeal membrane oxygenation (ECMO)  
2) Severe chronic respiratory disease requiring current use of home oxygen prior to 
COVID-19 diagnosis 
3) Pregnant or lactating  
4) Known hypersensitivity to dimethyl sulfoxide (DMSO)  
5) Unstable hemodynamics as deemed by the treating physician/investigator 
including but not limited to unstable , ventricular  tachycardia or new cardiac 
arrythmia requiring cardioversion 
6) Uncontrolled bacterial or fungal co-infection 
7) Any end-stage organ disease or condition, which in the opinion of the 
Investigator, makes the patient an unsuitable candidate for treatment 
8) Inability to obtain informed consent (from the patient or legally appropriate 
proxy) 
9) Presence of any contraindication to receiving prophylactic low dose 
unfractionated or low molecular weight heparin 
10) Respiratory failure not fully explained by cardiac failure or fluid  
overload.         
4 
Mesenchymal Stromal Cells (MSCs) Manufacturing 
     All manufacturing procedures will be performed in our GMP facility as dictated by Standard   
     Operating Protocols (SOP). Brief summaries are given here. 
 
4.1 
Source Material.  The cell product will consist of allogeneic mesenchymal stromal cells   
               MSCs) generated from the bone marrow of an eligible normal donor. Up to 100 ml of  
               marrow is obtained by aspiration under local anesthesia following informed consent.    
               The donor will meet the eligibility requirements as described in 21 CFR Parts 1271   
               Subpart C. Testing (Table 1) will be performed using FDA-approved, cleared and/or  
               licensed kits by Gulf Coast Regional Blood Center within 7 days of collection of the            

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               marrow for manufacturing. Manufacturing commences within four hours of marrow         
               collection by following SOP L03.05.XX. (Expansion of Human Mesenchymal Stromal 
Cells from Bone Marrow Using the Quantum Cell Expansion System).  
 
Table 1 Infectious Disease Testing on Marrow Donor 
Test 
Specification 
Chagas Disease  
Negative 
Hepatitis B Surface Antigen  
Negative 
Hepatitis B Core  
Negative 
Hepatitis C Virus  
Negative 
HIV 1 and 2  
Negative 
HTLV I and II  
Negative 
TAQ Screen MPX (HBV,HCV, HIV-1 Group M RNA, HIV-1 Group O)  
Negative 
NAT West Nile Virus  
Negative 
Serological Test for Syphilis  
Negative 
 
4.2 
Ex vivo cell expansion. In order to meet the cell dose requirements for the protocol, a  
              primary cell bank will be established. This will consist of MSCs cultured to passage 2           
              from the marrow using the Terumo Quantum Bioreactor (a Master File on this device  
              has been filed by Terumo BCT). This system avoids the multiple open procedures   
              associated with culturing the cells in cell culture flasks, thereby considerably decreasing  
              the risk of contamination. The cell culture bioreactor and all tubing are sterile and  
              completely disposable, thereby avoiding the possibility of cross-contamination. The  
              Quantum is capable of generating more than 1.5 billion MSC at Passage 2.  
4.3 
Freezing. For this proposal, we will use cells that were previously grown to   
              passage 2 and frozen in aliquots suitable for future expansion.  The pooled passage 2  
              cells were tested for sterility, endotoxin, and mycoplasma following previously  
              validated SOPs. The cells are frozen in Plasma Lyte containing a final concentration of  
              10% v/v DMSO using a controlled-rate freezer and stored in the vapor phase of liquid  
              nitrogen (SOP C03.34.XX).  The cell products for administration will be thawed Passage 
3 cells generated from aliquots of the Passage 2 frozen cell bank. Passage 2 cells will be  
              thawed and seeded into the Quantum bioreactor, cultured and harvested, washed,  
              counted, and cryopreserved using a controlled rate freezer in Plasma Lyte A containing  
 10% DMSO following standard operating procedures (SOPs L03.05.XX and C03.34.XX).  
 

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4.4 
 Testing. Products that meet study specific release criteria, as detailed on the certificate   
               of analysis (CofA), will be infused as per Section 4.0.  
5 
Patient Enrollment and Evaluation 
5.1 
Informed Consent 
                  Informed consent should be obtained prior to enrollment on the study. All patients  
                  and/or their legal guardian must sign a document of informed consent consistent  
                  with local institutional and federal guidelines stating that they are aware of the  
                  investigational nature of this protocol and of the possible side effects of treatment.  
                  Further, patients must be informed that no efficacy of this therapy is guaranteed, and  
                  that unforeseen toxicities may occur. Patients have the right to withdraw from this  
                  protocol at any time. No patient will be accepted for treatment without such a  
                  document signed by him or his legal guardian. Full confidentiality of patients and   
                  patient records will be provided according to institutional guidelines.  
5.2 
Registration and Randomization    
                 All consented patients will be registered in the online collaborative research    
                 environment (Forte’s OnCore® eResearch CTMS), a Clinical Research Management  
                 System available at BCM Dan L. Duncan Comprehensive Cancer Center.  Prior to  
                 enrollment in the study, the eligibility data must be reviewed and verified by the study  
                 coordinator and treating physician. After the eligibility status is verified, the subject    
                 will be assigned to a unique study sequence number. After safety run in, additional  
                 patients will be randomized in a 1:1 ratio to either the MSC or control arm.  
                 Randomization will use the permuted block method and be stratified by severity of  
                 ARDS (moderate and severe). Randomization information will be  
                 stored on a secure, access-restricted server at Baylor College of Medicine.   
5.3 
Treatment Plan 
5.3.1 Dosing 
 
   Patients who are randomized to the MSC arm will be administered an intravenous  
                infusion of MSCs at a dose of 1 x 108. A second infusion at the same dose will be  
allowed if the patient does not have  improvement in respiratory parameters per 
discretion of the investigator, or ARDS clinically worsens, within 3-5 days following the 
initial infusion. When a patient is enrolled on the protocol a sufficient number of 
aliquoted cells will be thawed to provide the required cell dose.  Thawing will be 
initiated on the planned date of administration according to the completed and signed 
Prescription for Administration received from  
                the Principle Investigator on the study or designee. The thawed cells will be pooled,  
                washed and formulated to the required final dose for administration. The release tests  
                will be performed on the pooled cells prior to administration. 
                

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5.3.2 Administration and Monitoring of MSC Infusion 
                The MSCs will be given by intravenous injection, and the IV flushed with saline upon   
                completion of the infusion. The expected volume is 20-30 mL.  The rate of infusion  
                may be tailored to patient fluid status, but the duration of infusion should not exceed   
                60 minutes.  No other medications should be given during the infusion unless  
                determined medically necessary by the treating physician.  Patients randomized to the  
                MSC arm must be receiving prophylactic low dose anticoagulation (or therapeutic                
                anticoagulation if indicated for a separate etiology [i.e. atrial fibrillation, venous  
                thromboembolism, etc.) or be considered eligible to receive at the time of study entry.  
                   
                  Patients may be pre-medicated with diphenhydramine up to 1mg/kg IV (max 50 mg)  
                  and/or acetaminophen up to 15mg/kg PO (max 650 mg) at least 30 minutes prior to   
                  infusion. 
 
                  Monitoring will be undertaken according to institutional standards for administration   
                  of blood products, and at a minimum will be monitored according to below: 
• Vitals signs (HR, BP, RR, oxygen saturation, and temperature) will be taken and 
recorded at the below times 
o Just prior to the start of the infusion 
o at 15, 30, 60, and 120 minutes (± 5 minutes) after the start of the 
infusion 
 
• During MSC administration, infusion should be stopped if: 
o   the patient shows signs or symptoms of worsening respiratory status    
   (such as tachypnea, cyanosis, complains of worsening shortness of  
   breath, etc.) regardless of the oximetry reading. 
o   there is an adverse event (AE) that the treating physician believes is 
   related to the MSC infusion. 
 
• No other medications should be given during the infusion unless determined 
medically necessary by the treating physician. 
 
• Infusion reactions should be managed per institutional standards.  
Appropriate medications should be readily available at the bedside, including 
epinephrine, hydrocortisone, and diphenhydramine.  
 
• If an anaphylactic reaction is suspected, the MSC administration should be 
stopped immediately and should not be resumed, nor should the patient 
receive any additional doses.  
5.3.3 Supportive Care for the control arm 
           Patients who are randomized to the control arm will receive supportive care or  
           treatment designated by their treating physicians

Version 4.2 (05-25-2022) 
16 
 
6 
Patient Evaluation 
6.1 
Study Calendar  
Treatment Protocol Days 
Pre-treatment 
(baseline) 
Day 0 
1 
2 
3 
4 
5 
6 
7 
14 
21 
28 
Visit window 
 
 
 
 
 
 
 
 
 
+2 
+2 
+2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
Demographics% 
X 
 
 
 
 
 
 
 
 
 
 
 
History*b 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
Xb 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
Xb 
Vital signsa 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
Xb 
Weight (kg) and height 
X 
 
 
 
 
 
 
 
 
 
 
 
MSC Infusion for MSC arm 
 
X 
 
 
X# 
X# 
X# 
 
 
 
 
 
APACHE II Score 
X 
 
 
 
 
 
 
 
 
 
 
 
SOFA/CURB-65 Score 
X 
 
 
 
 
 
 
 
 
 
 
Xc 
ARDS Assessmentc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6-point Ordinal Scale 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
Xb 
Xb 
Xb 
SAR-CoV-2 PCR 
X 
 
 
 
 
 
 
 
 
 
 
 
CBC w/ diff 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xd 
Xd 
Xd 
CMP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xd 
Xd 
Xd 
Coagulation Studies@ 
X 
Xe 
Xe 
 
Xe 
 
Xe 
 
Xe 
Xe 
Xe 
Xe 
LDH 
X 
Xe 
Xe 
 
Xe 
 
Xe 
 
Xe 
Xe 
Xe 
Xe 
C-Reactive Protein (CRP) 
X 
Xe 
Xe 
 
Xe 
 
Xe 
 
Xe 
Xe 
Xe 
Xe 
Research Cytokine Profile 
and labs 
 
X& 
X 
 
X 
 
X 
 
X 
Xd 
 
Xd 
Chest X-Ray/ Computerized 
Tomography (CT scan)e 
X 
Xe 
Xe 
 
Xe 
 
Xe 
 
Xe 
X 
X 
X 
Pregnancy test (if CBP) 
X 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Version 4.2 (05-25-2022) 
17 
 
a - vital signs to include HR, BP, Temp (max temp for the day), RR, Oxygen Saturation (O2 sat) 
b - Should be done daily if patient still hospitalized 
c - if remains in the ICU and ABG available per SOC. ARDS severity requires PaO2 to calculate 
d- only required if patient remains hospitalized at this time point 
e- done per SOC; not mandated by study. Date will be collected from medical record at these timepoints if available 
*- includes concurrent medications 
%- includes age, gender and ethnicity 
# - if inadequate response to initial infusion, a second infusion may be given within 3-5 days following the first infusion; no more than 2 infusions will be 
administered 
@ - coagulation studies = PT/aPTT, d-dimer, fibrinogen 
& - collected pre-infusion and 3-4 hours post-infusion

Version 4.2 (05-25-2022) 
18 
 
 
7 
Evaluations 
For patients randomized to the control arm, day 0 will be the day of randomization.  For 
patients randomized to the MSC arm, day 0 will be the day of infusion. Patients in both 
treatment arms will be evaluated as follows:  
7.1 
Baseline Pre-treatment Evaluation 
7.1.1 History and physical (including vitals and oxygenation requirements) 
7.1.2 SARS-CoV-2 RT-PCR testing 
7.1.3 ARDS assessment 
7.1.4 Complete Blood Count and differential (CBC) 
7.1.5 Complete Metabolic Panel (CMP) 
7.1.6 Coagulation studies: PT/aPTT, d-dimer, fibrinogen 
7.1.7 Lactate Dehydrogenase (LDH) 
7.1.8 C-Reactive Protein (CRP) 
7.1.9 CXR and/or CT chest imaging 
7.1.10 Urine or serum pregnancy test for females of childbearing potential 
7.1.11 APACHE II score 
7.1.12 Medical record review for concomitant medications 
7.1.13 Clinical status assessed by the six-category ordinal scale (1 ꞊ discharged; 6 ꞊ 
death)       
7.2 
Post-randomization/treatment Evaluation 
                  7.2.1.   History and physical (including vitals and oxygenation requirements)  
                               daily during hospitalization 
                  7.2.2    ARDS assessment daily day 0 through 7, then weekly until day 28 if remains 
                               intubated in the ICU or until extubated, whichever occurs first, and ABG data   
                               available 
                  7.2.2.   The following routine laboratory investigations will be obtained through day  
                                7, then weekly until day 28 or hospital discharge, whichever comes first 
• CBC  
• CMP   
                  7.2.3.   PT/aPTT, d-dimer, fibrinogen, CRP and LDH will be collected from the medical   
                                record, if available, at timepoints noted in the study calendar. 
                  7.2.4.   CXR and/or CT chest imaging will be done at baseline, then as  then as   
                               clinically indicated per treating physician discretion. Data will be collected  
                               from the medical record, if available, at timepoints noted in the study  
                              calendar. 
7.2.5.   SOFA/CURB-65 score day 0, and day 28, if patient remains in the ICU and ABG    
             available per SOC (for SOFA calculation). 
                  7.2.6.   Research cytokine profile and labs day 0 pre-infusion, 3-4 hours post-infusion,   
                               day 1, 3, 5, 7, 14 and day 28 if remains hospitalized. Optional if patient has  

Version 4.2 (05-25-2022) 
19 
 
                               been discharged.  
                  7.2.7.   Medical record review for data collection on supportive interventions,   
 
 
     including but not limited to:  
- 
Respiratory support (high flow nasal canula, AirVO, proning, high 
frequency oscillatory ventilation (HFOV), etc.) 
- 
Pharmacologic interventions (corticosteroids, vasopressors, 
paralytics, pulmonary vasodilators, etc.) 
                  7.2.8.    Medical record review for data collection on concurrent medications   
                                (such as antibiotics, antivirals, antihypertensives, anticoagulants),   
                                concurrent infections, and other end-organ damage daily   
                                through day 28 or hospital discharge, whichever occurs first 
                  7.2.10.   Clinical status assessed by the six category ordinal scale daily until  
                                  hospital discharge or death, whichever occurs first.                             
7.3 
Follow up          
                  7.3.1.  If discharged from the hospital prior to day 28, patients will followed up with   
                              (in clinic or by telephone) through day 28 as outlined in study calendar Section  
                              6.1. Additional visits or telephonic contacts will be obtained as clinically        
                             indicated for patients with toxicities deemed to be related to the MSC infusion,  
                             which will be followed until resolved. 
7.4 
Drug Toxicity and/or Adverse Reactions 
 
     7.4.1.   For consistency, toxicity for all patients will be evaluated using the NCI  
                               Common Toxicity Criteria scale (version 5.X; http://ctep.cancer.gov). 
 
 
                  7.4.2.   Adverse events will be collected as per SOP J02.05.XX and J02.75.XX. Data on                
                               all new adverse experiences/toxicities (regardless of seriousness) and   
                               worsening of baseline toxicities by at least one grade following infusion                   
                               will be collected for documentation purposes for 4 weeks after        
                               the last dosing of the study drug/biologic with the exception of all toxicities  
                               which were deemed to be related to the MSC infusion, which will be followed   
                               until resolved. 
 
                  7.4.3.   Serious Adverse event data will be collected and reported as per SOP                         
                               J02.06.XX until 28 days after the last dosing of study drug/biologic or until    
                               time of discharge, whichever comes first, and should consist of both  
                               solicited and volunteered events reported by the patient. 
 
                  7.4.4.   Infusion/allergic reactions will be evaluated by continuous monitoring the     
                               patient’s vital signs from the time of administration until two hours after  
                               starting the infusion.  
    
                 7.4.5.    Treatment-related serious adverse events (tSAE) will be considered as those   
                               directly related to the investigational infusion product. Adverse event grading  

Version 4.2 (05-25-2022) 
20 
 
                               will be as defined by the NCI Common Terminology Criteria for Adverse Events  
                               (CTCAE), Version 5. In making this assessment, there should be consideration  
                               of the probability of an alternative cause (for example, COVID-19 itself or  
                               some other condition preceding randomization) and the timing of the event  
                               with respect to study treatment. The safety endpoint of the study is tSAE,  
                               defined as:  
- Any grade 5 AE  
- Any grade 4 AE that fails to return to grade 2 within 72 hours post-infusion 
- Grade 2 to 4 allergic reactions (severe rash, bronchospasm, and immediate-
type allergic reactions) 
- Arterial or venous thromboembolic event occurring within 48 hours of 
infusion 
- Serious Adverse Event (SAE) that, in the treating physicians’ judgment, is 
considered related to MSC infusion and requires withdrawal from the study 
 
8 
Statistical Considerations  
8.1 
   Clinical Trial Design 
This is a single-center, open label, non-blinded randomized controlled, parallel study 
designed to evaluate the safety and clinical benefits of banked, allogeneic bone marrow 
MSCs versus  control (routine supportive care) for treatment of COVID-19 related ARDS. The 
primary safety endpoint will be treatment-related serious adverse events (tSAE), defined in 
Section  7.4.5. The primary efficacy endpoint will be improvement in clinical status by at 
least two  categories at day 14 post randomization, assessed by a six-category ordinal scale. 
The study will first enroll and treat 6 patients with MSCs for safety run in, then additional 60 
patients will be randomized to receive either MSCs or supportive care designated by their 
treating physician. 
8.2 
  Sample size 
      This early phase study will accrue a total of 66 patients with 6 patients for safety run in and    
      additional 30 patients in each treatment arm by randomization. MSCs will be manufactured   
      in our GMP facility and available to treat at least 36 patients. The study primary efficacy   
      endpoint is improvement in clinical status at least two categories on a six-category ordinal  
      scale at day 14 post randomization. The six-category ordinal scale ranges from 6 to 1 with a  
      higher score indicates worse clinical outcome, i.e. 6 ꞊ death; 5 ꞊ hospitalization, requiring  
      ECMO and/or IMV; 4 ꞊ hospitalization, requiring NIV and/or HFNC therapy; 3 =  
      hospitalization, requiring supplemental oxygen (but not NIV/HFNC); 2 = hospitalization, not  
      requiring supplemental oxygen; 1 = hospital discharge. The scale will be used to evaluate  
      patients’ status daily from baseline to day hospital discharge. Patients’ clinical status at day  
      14 post randomization will be dichotomized as ‘improved’ (decreased by at least two  
      categories) or ‘not improved’. Patients who died before day 14 will be deemed as ‘not  
      improved’. Public data about the novel COVID-19 are limited and the data varies between all   
      studies. Based on reported data, the time to improvement in patients with supportive care   
      were about 22-23 days [20, 82] we expect 10% patients in the control group and 35%  

Version 4.2 (05-25-2022) 
21 
 
     patients in the MSC group will achieve ‘improved’ status at day 14, a total sample size of  
     66 (36 in the MSC arm and 30 in the control arm) will provide 84% power to detect a  
     difference in clinical improvement of 25% between control (10%) and MSC (35%) at a 7.5%   
     one-sided significance level using a Chi-square test.  
8.3 
    Randomization and Stratification  
   After safety run in, patients will be randomized in a 1:1 ratio to receive either MSCs or    
   supportive care.  Randomization will be stratified by severity of ARDS (moderate and severe),  
   and employ permuted blocks method.  
8.4 
 Safety monitoring and stopping rule 
  This study will enroll the first 6 patients to the MSC arm for safety run in. Based on experience,  
  we expect the toxicity of MSC is low about 5-10%. The chance of observing tSAEs in more than  
  two out of six patients is 1.6%. After the first six patients complete safety monitoring at day  
  28, we will halt the study if more than two patients have tSAEs. Otherwise, the study will  
  continue to enroll additional patients 
 
The study will continuously monitor the safety of MSCs infusions in patients who are 
randomized to the MSC arm so that the accrual can be halted early if there is an unexpectedly 
high rate of treatment-related serious adverse events (tSAE) at day 28, defined in Section 
7.4.5.  Patients who don’t complete the 28-day observation due to a reason other than tSAE 
will be deemed not evaluable for tSAE. However, those patients in the randomization phase 
are evaluable for efficacy and will not be replaced. A tSAE rate of greater than or equal to 25% 
is considered excessive. The occurrence of tSAEs will be monitored using a stopping guideline 
based on a Pocock-type boundary method [83]. The following sequential stopping boundaries 
will be used: 
 
Number of 
Patients 
1-3 
4-5 
6-7 8-9 
10-
12 
13-
14 
15-
17 
18-
20 
21-
23 
24-
26 
27-
28 
29-
30 
Number of tSAEs < 
- 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
 
  The accrual will be halted if the number of tSAEs is equal to or exceeds the boundary in the  
  above table. Under this sequential stopping rule, the probability of early stopping is 5% if the   
  true tSAE rate is 25%, and the probability of early stopping will be high at 81% if the true tSAE  
  rate is 50%. 
8.5 
   Statistical Analysis 
   All patients who received any MSC infusions in the MSCs arm or supportive care in the control  
   arm will be included in the safety analyses.  All efficacy analysis will be based on the intent to  
   treat (ITT) population, defined as eligible and randomized subjects.   
 
   Adverse event data and corresponding toxicity grades after treatment will be    
   summarized descriptively by treatment arms. All adverse events, grades, and attributions  

Version 4.2 (05-25-2022) 
22 
 
   will be listed and tabulated. Toxicity information including the type, severity, time of onset,   
   time of resolution, and the probable association with the study regimen will be tabulated and  
   summarized by treatment arms.  Rate of tSAEs in patients treated with MSCs will be reported  
as proportion and its 95% confidence interval overall and by cancer status (cancer patients 
versus non-oncologic patients).    
 
   Clinical outcome data (increase in oxygen saturation, decrease in oxygen supplementation,   
   progression to mechanical ventilation or ECMO, evolution of other end-organ damage,  
   severity of ARDS, mortality rate, cause of death, duration on ventilation, durations of ICU stay  
and hospital stay, duration of vasopressor use, negative SARS-Co-V-2 RT-PCR by day 28, and 
change in disease severity scores and corticosteroid use) will be summarized descriptively. 
Categorical variables will be summarized by frequencies and percentages. Continuous 
variables will be summarized by means, standard deviations, medians, interquartile ranges.  
 
   Proportion of patients who have an improvement of at least two categories on a six category   
   ordinal scale at day 14 and day 28 will summarized using rate and their 95% confidence  
interval by treatment arms and compared with Chi-square tests. Proportion of patients with 
improvement will also be reported by cancer status. As exploratory analyses,  
   improvement in clinical status will also be assessed using logistic regression, adjusting for  
   potential confounders such as age, race/ethnicity, underline condition, and severity of ARDS.   
   Changes in the six-point ordinal scale, oxygen saturation, required FiO2, severity scores from  
   baseline will be presented graphically and compared with paired t-tests or Wilcoxon singed  
   rank tests, whichever are appropriate (comparisons are considered exploratory).  Duration of  
   overall survival will be days from date of randomization to date of death or date of last follow- 
   up for censoring.  Overall survival will be calculated using Kaplan-Meier survival curves with  
   estimates of medians and 95% confidence intervals by each treatment arm and compared  
   with a log-rank test (comparison is considered exploratory). 
    
   Laboratory data, which include inflammatory markers and chest imaging will be reported with  
   appropriate summary statistics. Changes from baseline to post-treatment will be plotted for  
   each patient over time and assessed using paired test methodologies when appropriate.  
   Comparison between the two treatment groups will be exploratory with appropriate two- 
   sample tests.   
9 
Off Treatment and Off Study Criteria 
9.1 
Off Treatment Criteria 
9.1.1.  Infusion related anaphylactic reactions 
9.1.2.  Occurrence of thrombotic event within 48 hours after initial infusion 
9.1.3.  Patient/legal guardian decline second infusion 
9.1.4.  Treating physician determines second infusion would not be beneficial for patient 

Version 4.2 (05-25-2022) 
23 
 
9.2 
Off Study Criteria 
9.2.1.  Completion of all study specified procedures  
9.2.2.  Refusal of further study follow-up by patient or legal guardian  
             9.2.3.  Lost to follow up 
             9.2.4.  Death  
10 Clinical Trial Oversight and Monitoring 
         10.1.   This protocol will be conducted in accordance with the Cell and Gene Therapy   
                     Monitoring Plan on file with the FDA.    
      
         10.2.   This protocol will be monitored in accordance with the current Dan L Duncan  
                      Cancer Center Data Safety Monitoring Board Plan. 
 
         10.3.    The conduct of this clinical trial will be evaluated in accordance with the Texas  
                      Children's Cancer Center for Cell and Gene Therapy Quality    
                      Assurance/Quality Control Policy and Procedure Plans.  
 

Version 4.2 (05-25-2022) 
24 
 
 
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