Combined Kidney and Bone Marrow Transplantation to Preven... | NCT00801632

NCT00801632

Status Module

Name	Class
Immune Tolerance Network (ITN)	NETWORK

Oversight Module

Description Module

Detailed Description

All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.

Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.

Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.

Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.

Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Kidney and Marrow Recipients	Experimental	Combined kidney and bone marrow transplant	Procedure: Kidney Transplantation Procedure: Bone marrow transplantation Biological: MEDI-507 Drug: cyclophosphamide Biological: rituximab Drug: Tacrolimus Drug: corticosteroids Radiation: thymic irradiation

Name	Type	Description	Arm Group Labels	Other Names
Kidney Transplantation	Procedure	Surgical transplantation of donor kidney	Kidney and Marrow Recipients

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks	A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.	48 months post-transplant

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Experiencing Acute Rejection	The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.

Eligibility Module

Name	Affiliation	Role
David Sachs, MD	Massacusetts General Hospital	Principal Investigator
Ben Cosimi, MD	Massachusetts General Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
18216355	Background	Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.
23656665

Label	URL
Immune Tolerance Network	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Units	Counts
Participants	BG0005

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG0005
>=65 years	BG000

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00032.8± 8.6

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003
Male	BG0002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000
Not Hispanic or Latino	BG0005

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG0001

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0005

Baseline Creatinine Level

Baseline creatinine is defined as the lowest serum creatinine collected during the stabilization period or in the 4 weeks following the end of the stabilization period. The stabilization period is defined as 4 consecutive creatinine values close in value (not differing more than 0.3). A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG0001.9± 1.2

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

Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks

A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.

Intent-to-treat

Posted

Number

participants

48 months post-transplant

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Units	Counts
Participants	OG0005

Title

Denominators

Categories

Title	Measurements
	OG0003

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						Percentage of Participants	60.0			2-Sided	95	14.7	94.7			Clopper-Pearson used to derive confidence interval	No	Superiority or Other

Secondary

Percentage of Participants Experiencing Acute Rejection

The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.

Intent-to-treat

Posted

Number

95% Confidence Interval

Percentage of Participants

Transplantation until study completion or participant termination (up to five years)

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Change in Renal Function

Change in renal function as seen in serum creatinine values from baseline until study completion or participant termination. Baseline is defined as the lowest serum creatinine collected during stabilization period or in the four weeks following the end of the stabilization period. The stabilization period is defined as four consecutive creatinine values close in value (not differing more than 0.3 mg/dL). Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.

Intent-to-treat

Posted

Mean

Standard Deviation

mg/dL

Transplantation until study completion or participant termination (up to five years)

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Percentage of Participants With Graft Survival Through 156 Weeks

The percentage of participants with graft survival from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded. Graft survival is defined as the time to week 156 or graft loss. Graft loss is defined as the day on which a graft is deemed irreversibly nonfunctional and dialysis is begun, a transplantectomy is performed, or the participant is re-transplanted, whichever comes first. Six consecutive weeks of dialysis are required for the diagnosis of graft loss, though the date of graft loss will be defined as the date of first dialysis.

Participants who were followed at least three years after transplantation or experienced graft loss prior to week 156

Posted

Number

95% Confidence Interval

Percentage of Participants

Transplantation until week 156

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Percentage of Participants Surviving Through 156 Weeks

The percentage of participants who survived from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded.

Participants who were followed at least three years after transplantation or experienced death prior to week 156

Posted

Number

95% Confidence Interval

Percentage of Participants

Transplantation until week 156

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Time to Neutrophil Recovery Following Transplant

Time (in days) until neutrophil recovery following transplant. Neutrophil recovery is defined as an absolute neutrophil count (ANC) > 500/mm^3 at three consecutive assessments on different days post-transplant. Time to recovery is time from transplantation until the first assessment date used to confirm the recovery.

Intent-to-treat

Posted

Mean

Standard Deviation

days

Transplantation until study completion or participant termination (participants followed up to five years)

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Time to Platelet Recovery Following Transplant

Time (in days) until platelet recovery following transplant. Platelet recovery is defined as a platelet count >20,000 /mm^3 and where no transfusion is required. Time to recovery is time from transplantation until platelet value recovers.

Intent-to-treat

Posted

Mean

Standard Deviation

days

Transplantation until study completion or participant termination (participants followed up to five years)

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Secondary

Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection

Clinically significant invasive or resistant opportunistic infections include cytomegalovirus, herpes zoster, and candida.

Intent-to-treat

Posted

Number

95% Confidence Interval

Percentage of Participants

Transplantation until study completion or participant termination (participants followed up to five years)

ID	Title	Description
OG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.

Units

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MEDI-507	Recipients received a conditioning treatment that started with rituximab (375 mg/m^2 infusion) on days -7, -2, 5 and 12. Cyclophosphamide (60 mg/kg) on days -5 and -4, followed by hemodialysis. MEDI-507, a T-cell-depleting agent, was given at 0.1 mg/kg on day -2 and 0.6 mg/kg on days -1, 0 and 1. Thymic irradiation (700 cGy) was given on day -1. Recipients underwent surgical transplantation of a donor kidney on day 0. During kidney transplant, bone marrow cells donated by the same donor as the kidney were given through a plastic tube placed in a vein in the chest, underneath the collarbone. Prednisone was started at 2 mg/kg/day on day 4 and tapered off by day 20. A steroid pulse (methylprednisolone 500 mg) was given on days 10, 11, and 12. Tacrolimus (0.05 mg/kg twice a day, adjusted to trough level of 10-15 ng/mL) was given starting on day -1. When the subject met weaning criteria, tacrolimus was tapered over a period of no less than 8 weeks beginning 60 days post-transplant.			5	5	5	5

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Engraftment syndrome	Immune system disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected5 at risk
Transplant rejection	Immune system disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Gastroenteritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Viral infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Blood creatinine increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Haematoma	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Thrombosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0006 events1 affected5 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected5 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Gastritis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Catheter related complication	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Catheter site infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0004 events3 affected5 at risk
Drug toxicity	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Weight increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected5 at risk
Proteinuria	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected5 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected5 at risk

Ancestor Terms

ID	Term
D017582	Renal Replacement Therapy
D013812	Therapeutics
D016377	Organ Transplantation
D014180	Transplantation
D013514	Surgical Procedures, Operative
D013520	Urologic Surgical Procedures
D013519	Urogenital Surgical Procedures
D016378	Tissue Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D018942	Macrolides
D007783	Lactones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D011239	Prednisolone
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D011244	Pregnadienediols

ID	Term
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D016030	Kidney Transplantation
D016026	Bone Marrow Transplantation
C544394	siplizumab
D003520	Cyclophosphamide
D000069283	Rituximab
D016559	Tacrolimus
D000305	Adrenal Cortex Hormones
D008775	Methylprednisolone
D011241	Prednisone