A Prospective Study of Remestemcel-L, Ex-vivo Cultured Ad... | NCT02336230

Name	Class
Quintiles, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Remestemcel-L 2×10^6 MSCs/kg	Experimental	Participants were treated with intravenous (IV) remestemcel-L at a dose of 2×10^6 mesenchymal stromal cells (MSCs)/kilogram (kg) actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.	Drug: remestemcel-L

Name	Type	Description	Arm Group Labels	Other Names
remestemcel-L	Drug	Participants were treated with IV remestemcel-L at a dose of 2 x 10^6 MSC/kg (actual body weight at screening) twice per week for each of 4 consecutive weeks. Infusions were administered at least 3 days apart and no more than 5 days apart for any infusion.

Measure	Description	Time Frame
Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy	ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.	Day 28

Measure	Description	Time Frame
Overall Survival (OS) Rate at Day 100 Post Initiation of Therapy	Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.	Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Responder Status at Day 28

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant is diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The participant may have Grade C or D aGVHD involving the skin, liver, and/or GI tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.
Participant has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D [International Bone Marrow Transplant Registry (IBMTR) grading] aGVHD that shows progression within 3 days, or no improvement within 7 days of consecutive treatment with 2 mg/kg/day methylprednisolone or equivalent.
Participant must be able to be treated with remestemcel-L within 4 days of signing of informed consent.
Participants who have had persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/kg/day (for participants >50 kg) or <30 mL/kg/day (for participants ≤50 kg). See GVHD Organ Severity Criteria (Table 2) for values in mL/m^2. In the absence of nausea or vomiting, participants could have been considered to have Grade B GVHD if:
1. other causes of diarrhea had been ruled out (eg, Clostridium difficile, adenovirus or cytomegalovirus [CMV] infection, or oral magnesium administration), and if
2. the low stool volume reflected the effects of fasting, narcotics, or antidiarrheal medications.
Participant must have adequate renal function as defined by a calculated creatinine clearance of >30 mL/min per 1.73 m^2. For participants 1 to 18 years of age, creatinine clearance is calculated using the Bedside Schwartz equation:

Glomerular filtration rate (GFR, in mL/min per 1.73 m^2) = (0.413 * height [cm])/serum creatinine (mg/dL)

For participants younger than 1 year of age, renal function is determined using the Schwartz equation adjusted for this age group:

Creatinine clearance (mL/min per 1.73 m^2= (height [cm] x 0.45)/ (serum creatinine [mg/dL]).
Participant has a minimum Karnofsky/Lansky Performance Level of at least 30 at the time of study entry.
Participant (or legal representative where appropriate) must be capable of providing written informed consent.
Female participants of childbearing potential (≥10 years of age) are required to use a medically accepted method of contraception and to agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
Male participants with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study, including the follow-up time period.
The participant must be willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation during the study period, as specified in this protocol.

Exclusion Criteria:

Participant has Grade B aGvHD with skin-only involvement.
Participant has received any second line therapy to treat aGVHD prior to screening.
Participant has received systemic agents other than steroids and prophylactic agents for primary treatment of aGVHD.
Participant shows evidence of diffuse alveolar hemorrhage or other active pulmonary disease, which is likely to require more than 2L of oxygen via face mask, or an estimated fractional inspired oxygen concentration (FiO2) of 28% via other delivery methods in order to sustain an O2 saturation of 92%.
Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant including but not limited to uncontrolled infection, heart failure, or pulmonary hypertension.
Participant has received any stem cell agents (other than hematopoietic graft) during study participation or within 30 days prior to study entry. Previous use of irradiated granulocytes within 30 days is permitted.
Participant has received an HSCT transplant for a solid tumor disease.
Participant has had prior treatment with mesenchymal stem cells (MSCs), including remestemcel-L.
Participant shows evidence of severe (required treatment) hepatic veno-occlusive disease (VOD) or sinusoidal obstruction at screening.
Participant had positive laboratory test results indicating infection with the human immunodeficiency virus (HIV) at any time and/or active hepatitis B or C virus infection within 3 months prior to screening.
Participant shows evidence of encephalopathy, as defined by a change in mental status since the onset of aGVHD.
Participant is a female who is pregnant, lactating, or is planning a pregnancy during study participation, or in the follow-up period.
Participant currently being treated for a solid tumor malignancy.
Participant has participated in any interventional clinical trial for an aGVHD therapeutic agent. However, in exceptional cases, experimental agents may have been administered to enrolled participants at the Investigator's discretion.
Participant has participated or is currently participating in any autologous and allogeneic stem cell or gene therapy study for the treatment of aGVHD. Participants participating in investigative protocols aimed at modification of the transplant graft (such as T-cell depletion) or aimed at modification of the conditioning regimen are allowed in the study.
Participant has a known hypersensitivity to dimethyl sulfoxide (DMSO) or to murine, porcine, or bovine proteins.

Name	Affiliation	Role
Christopher James	Mesoblast, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital Los Angeles		Los Angeles	California	90027	United States
Children's Hospital of Orange County

PubMed Identifier	Type	Citation	Retractions
32018062	Derived	Kurtzberg J, Abdel-Azim H, Carpenter P, Chaudhury S, Horn B, Mahadeo K, Nemecek E, Neudorf S, Prasad V, Prockop S, Quigg T, Satwani P, Cheng A, Burke E, Hayes J, Skerrett D; MSB-GVHD001/002 Study Group. A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 May;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018. Epub 2020 Feb 1.

ID	Title	Description
FG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with intravenous (IV) remestemcel-L at a dose of 2×10^6 mesenchymal stromal cells (MSCs)/kilogram (kg) actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 8, 2018

ID	Title	Description
BG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants	BG00055

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy

ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.

FAS included all participants who provided informed consent, were screened, and were found eligible to enter the study.

Posted

Number

percentage of participants

Day 28

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants	OG00055

Title

Denominators

Categories

Title	Measurements
	OG00069.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Binomial Distribution		0.0003	P-value was calculated from the binomial distribution under the assumption of a 0.45 success rate for the null hypothesis.													Other

Secondary

Overall Survival (OS) Rate at Day 100 Post Initiation of Therapy

Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.

FAS included all participants who provided informed consent, were screened, and were found eligible to enter the study.

Posted

Number

percentage of participants

Day 100

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants	OG000

Secondary

OS Rate at Day 100 Post Initiation of Therapy, Stratified by Responder Status at Day 28

Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.

FAS included all participants who provided informed consent, were screened, and were found eligible to enter the study. Number analyzed is the number of participants with data available for given category.

Posted

Number

percentage of participants

Day 100

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants	OG000

Secondary

OS Rate at Day 100 Post Initiation of Therapy, Stratified by Baseline aGVHD Grade

OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. Maximum severity of acute GVHD was assessed by using International Bone Marrow Transplant Registry (IBMTR) index. The severity index was defined as: Grade A (skin Stage 1: extent of rash <25%); Grade B (skin Stage 2: extent of rash 25 to 50% or liver Stage 1 to 2: total bilirubin 34 to 102 micromoles per liter [mcmol/L] or intestinal tract Stage 1 to 2: volume of diarrhea 550 to 1500 milliliters per day [mL/day]); Grade C (skin Stage 3: extent of rash > 50% or liver Stage 3: total bilirubin 103 to 255 mcmol/L or intestinal tract Stage 3: volume of diarrhea >1500 mL/day); Grade D (skin Stage 4: extent of rash bullae or liver Stage 4: total bilirubin >255 or intestinal tract Stage 4: volume of diarrhea severe pain and ileus).

Posted

Number

95% Confidence Interval

percentage of participants

Day 100

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Secondary

OS Rate at Day 100 Post Initiation of Therapy, Stratified by Organ Involvement

OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. The data was summarized for organ involvement: skin only, lower GI only, and multi-organ.

Posted

Number

percentage of participants

Day 100

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants

Secondary

OR Rate at Day 56 and 100 Post Initiation of Therapy

OR rate was defined as the percentage of participants who had achieved overall response. Overall response was defined as CR plus PR as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.

FAS included all participants who provided informed consent, were screened, and were found eligible to enter the study.

Posted

Number

percentage of participants

Day 56 and Day 100

ID	Title	Description
OG000	Remestemcel-L 2×10^6 MSCs/kg	Participants were treated with IV remestemcel-L at a dose of 2×10^6 MSCs/kg actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Cardiac arrest	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pericardial effusion	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Jejunal perforation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Asthenia	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Acute graft versus host disease	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Graft versus host disease in skin	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Graft versus host disease	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Staphylococcal infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
BK virus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Human herpesvirus 6 infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Adenovirus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Cellulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Enterococcal infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Epstein-Barr viraemia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Fungaemia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Fungal infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Lactobacillus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Rotavirus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Platelet count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
White blood cell count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Hypermetabolism	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Acute myeloid leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Acute megakaryocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Somnolence	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected54 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Capillary leak syndrome	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Hypertensive crisis	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk
Venoocclusive disease	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected54 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Pericardial effusion	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Tachycardia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Cushingoid	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00010 affected54 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0009 affected54 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected54 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Flatulence	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG00013 affected54 at risk
Oedema peripheral	General disorders	MedDRA 20.0	Systematic Assessment	EG0007 affected54 at risk
Generalised oedema	General disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Chronic graft versus host disease	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected54 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected54 at risk
Graft versus host disease in skin	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Adenovirus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG00010 affected54 at risk
Epstein-Barr viraemia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0007 affected54 at risk
BK virus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Oral candidiasis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Pneumonia fungal	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Transaminases increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0007 affected54 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0007 affected54 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected54 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected54 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Tremor	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Agitation	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Insomnia	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected54 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Dysuria	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0007 affected54 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected54 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected54 at risk
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG00010 affected54 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected54 at risk