A Phase 2, Multicenter, Open-label Study of MEDI-551 in A... | NCT01466153

Label	Type	Description	Intervention Names
Rituximab + Bendamustine	Active Comparator	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.	Drug: Rituximab Drug: Bendamustine
MEDI-551 2 mg/kg + Bendamustine	Experimental	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.	Drug: Bendamustine Drug: MEDI-551
MEDI-551 4 mg/kg + Bendamustine	Experimental	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.	Drug: Bendamustine Drug: MEDI-551

Name	Type	Description	Arm Group Labels	Other Names
Rituximab	Drug	Rituximab was administered by IV infusion as a dose of 375 mg/m^2 on Day 2 of Cycle 1 and then at 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycles	Rituximab + Bendamustine

Measure	Description	Time Frame
Objective Response Rate	ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.

Name	Affiliation	Role
MedImmune	MedImmune LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama		United States
Research Site

ID	Title	Description
FG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.

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

Objective Response Rate

ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Number

95% Confidence Interval

Percentage of Participants

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Units	Counts
Participants	OG00062 OG00136 OG00261

Title

Denominators

Categories

Title	Measurements
	OG00059.7(46.4 to 71.9) OG00152.8(35.5 to 69.6) OG00263.9(50.6 to 75.8)

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 OG002		Cochran-Mantel-Haenszel		0.4475														Superiority or Other

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.

The safety population includes all participants who received any investigational product.

Posted

Number

Participants

From time of consent to 90 days post last dose

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.

Secondary

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.

The safety population includes all participants who received any investigational product.

Posted

Number

Participants

From time of consent to 90 days post last dose

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002

Secondary

Number of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs

AEs observed in participants with clinically significant ECG abnormalities were assessed.

The safety population includes all participants who received any investigational product.

Posted

Number

Participants

From time of consent to 90 days post last dose

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Secondary

Complete Response Rate

Complete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Number

95% Confidence Interval

Percentage of Participants

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine

Secondary

Minimal Residual Disease Negative Complete Response (CR) Rate

The MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Number

95% Confidence Interval

Percentage of Participants

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Secondary

Time to Response

Time to response was evaluated using the Kaplan-Meier method.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Median

95% Confidence Interval

Months

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Secondary

Time to Disease Progression (TTP)

TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Median

95% Confidence Interval

Months

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine

Secondary

Progression Free Survival (PFS)

PFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Median

95% Confidence Interval

Months

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG002	MEDI-551 4 mg/kg + Bendamustine

Secondary

Overall Survival (OS)

OS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.

Intent-to-treat (ITT) population includes all participants who were randomized into the study.

Posted

Number

95% Confidence Interval

Months

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
OG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Secondary

Number of Participants Who Developed Detectable Anti-drug Antibodies (ADA)

A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.

The safety population includes all participants who received any investigational product. Participants whom ADA samples were available were analyzed for this outcome measure.

Posted

Number

Participants

From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)

ID	Title	Description
OG000	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG001	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Secondary

Terminal Half Life (t1/2) of MEDI-551

Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.

The safety population includes all participants who received any investigational product. Participants whom PK samples were available were analyzed for this outcome measure.

Posted

Mean

Standard Deviation

Day

Pre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1

ID	Title	Description
OG000	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
OG001	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Units

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0006 events6 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Atrioventricular block	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Cardiac failure	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Thyroglossal cyst	Congenital, familial and genetic disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Uveitis	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Ascites	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Asthenia	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Inflammation	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0023 events1 affected57 at risk
Abdominal infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0015 events4 affected33 at risk EG0021 events1 affected57 at risk
Pneumonia pseudomonal	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Pneumonia viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Rhinovirus infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Sepsis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Skin infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Viral myocarditis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG00110 events5 affected33 at risk EG00214 events5 affected57 at risk
Haemoglobin decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0012 events1 affected33 at risk EG0020 events0 affected57 at risk
Platelet count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Coma	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Syncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Renal failure	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Female genital tract fistula	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events1 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Hypotension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG00064 events18 affected60 at risk EG00120 events7 affected33 at risk EG00213 events9 affected57 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0005 events4 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG00026 events3 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG00026 events4 affected60 at risk EG0017 events3 affected33 at risk EG0025 events1 affected57 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG00078 events28 affected60 at risk EG00144 events10 affected33 at risk EG00258 events19 affected57 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG00076 events12 affected60 at risk EG0018 events5 affected33 at risk EG00221 events10 affected57 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0020 events0 affected57 at risk
Tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Vision blurred	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events3 affected60 at risk EG0012 events2 affected33 at risk EG0021 events1 affected57 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0021 events1 affected57 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0008 events7 affected60 at risk EG0013 events3 affected33 at risk EG00215 events7 affected57 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 events5 affected60 at risk EG0011 events1 affected33 at risk EG0023 events3 affected57 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00023 events20 affected60 at risk EG00111 events9 affected33 at risk EG00211 events10 affected57 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00020 events13 affected60 at risk EG0015 events5 affected33 at risk EG00215 events11 affected57 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0025 events4 affected57 at risk
Flatulence	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events3 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Gingival pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00045 events29 affected60 at risk EG00123 events13 affected33 at risk EG00247 events29 affected57 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00014 events13 affected60 at risk EG0018 events7 affected33 at risk EG0027 events7 affected57 at risk
Asthenia	General disorders	MedDRA 18.1	Systematic Assessment	EG00031 events20 affected60 at risk EG0014 events4 affected33 at risk EG00217 events7 affected57 at risk
Chest discomfort	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Chills	General disorders	MedDRA 18.1	Systematic Assessment	EG00015 events11 affected60 at risk EG0017 events6 affected33 at risk EG00210 events7 affected57 at risk
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG00038 events18 affected60 at risk EG00119 events14 affected33 at risk EG00230 events20 affected57 at risk
Oedema peripheral	General disorders	MedDRA 18.1	Systematic Assessment	EG0004 events3 affected60 at risk EG0013 events2 affected33 at risk EG0027 events7 affected57 at risk
Peripheral swelling	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 events1 affected60 at risk EG0012 events1 affected33 at risk EG0022 events1 affected57 at risk
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG00027 events20 affected60 at risk EG00114 events11 affected33 at risk EG00223 events14 affected57 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0012 events2 affected33 at risk EG0022 events1 affected57 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0022 events1 affected57 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0014 events3 affected33 at risk EG0024 events4 affected57 at risk
Conjunctivitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Lung infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0005 events3 affected60 at risk EG0013 events2 affected33 at risk EG0025 events4 affected57 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0011 events1 affected33 at risk EG0025 events4 affected57 at risk
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0012 events2 affected33 at risk EG0020 events0 affected57 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0026 events6 affected57 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0014 events3 affected33 at risk EG0021 events1 affected57 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0008 events3 affected60 at risk EG0010 events0 affected33 at risk EG0023 events1 affected57 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0023 events3 affected57 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG00025 events14 affected60 at risk EG00164 events21 affected33 at risk EG002123 events37 affected57 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0003 events1 affected60 at risk EG0010 events0 affected33 at risk EG0024 events3 affected57 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0004 events1 affected60 at risk EG0010 events0 affected33 at risk EG0024 events3 affected57 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0003 events1 affected60 at risk EG0012 events1 affected33 at risk EG0022 events2 affected57 at risk
Blood creatinine increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0013 events2 affected33 at risk EG0021 events1 affected57 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0007 events4 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0004 events1 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Lymphocyte count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0008 events3 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Neutrophil count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG00016 events9 affected60 at risk EG0013 events1 affected33 at risk EG0026 events3 affected57 at risk
Platelet count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0004 events2 affected60 at risk EG0012 events2 affected33 at risk EG0022 events2 affected57 at risk
Weight decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0006 events5 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
White blood cell count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG00017 events13 affected60 at risk EG0014 events4 affected33 at risk EG0026 events6 affected57 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0013 events3 affected33 at risk EG0020 events0 affected57 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0013 events2 affected33 at risk EG0021 events1 affected57 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0011 events1 affected33 at risk EG0023 events2 affected57 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0005 events3 affected60 at risk EG0016 events5 affected33 at risk EG0022 events2 affected57 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 events2 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0007 events6 affected60 at risk EG0011 events1 affected33 at risk EG0024 events4 affected57 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0012 events2 affected33 at risk EG0021 events1 affected57 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0007 events7 affected60 at risk EG0011 events1 affected33 at risk EG0024 events4 affected57 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected60 at risk EG0014 events4 affected33 at risk EG0028 events5 affected57 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0011 events1 affected33 at risk EG0029 events5 affected57 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0009 events5 affected60 at risk EG0011 events1 affected33 at risk EG0029 events7 affected57 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0012 events2 affected33 at risk EG0022 events2 affected57 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0012 events2 affected33 at risk EG0022 events2 affected57 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0006 events3 affected60 at risk EG0010 events0 affected33 at risk EG0025 events4 affected57 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0022 events2 affected57 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0013 events2 affected33 at risk EG0023 events3 affected57 at risk
Dizziness	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected60 at risk EG0016 events3 affected33 at risk EG00210 events7 affected57 at risk
Dysgeusia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0007 events5 affected60 at risk EG0013 events3 affected33 at risk EG0021 events1 affected57 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0009 events7 affected60 at risk EG0019 events6 affected33 at risk EG0026 events5 affected57 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0010 events0 affected33 at risk EG0022 events1 affected57 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0011 events1 affected33 at risk EG0021 events1 affected57 at risk
Sciatica	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0023 events2 affected57 at risk
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected60 at risk EG0010 events0 affected33 at risk EG0025 events4 affected57 at risk
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0013 events3 affected33 at risk EG0022 events2 affected57 at risk
Insomnia	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0007 events6 affected60 at risk EG0012 events2 affected33 at risk EG0025 events5 affected57 at risk
Dysuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0005 events4 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected60 at risk EG0012 events2 affected33 at risk EG0021 events1 affected57 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00013 events11 affected60 at risk EG0019 events5 affected33 at risk EG00224 events19 affected57 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0020 events0 affected57 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00013 events9 affected60 at risk EG0012 events2 affected33 at risk EG0025 events4 affected57 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events3 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events3 affected60 at risk EG0011 events1 affected33 at risk EG0024 events3 affected57 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0011 events1 affected33 at risk EG0022 events2 affected57 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0012 events2 affected33 at risk EG0021 events1 affected57 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events1 affected60 at risk EG0010 events0 affected33 at risk EG0022 events2 affected57 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0011 events1 affected33 at risk EG0023 events3 affected57 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0010 events0 affected33 at risk EG0021 events1 affected57 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected60 at risk EG0012 events2 affected33 at risk EG0022 events2 affected57 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0010 events0 affected33 at risk EG0026 events6 affected57 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0007 events7 affected60 at risk EG0013 events3 affected33 at risk EG0023 events2 affected57 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0006 events5 affected60 at risk EG0011 events1 affected33 at risk EG0020 events0 affected57 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 events9 affected60 at risk EG0019 events5 affected33 at risk EG0026 events6 affected57 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0007 events4 affected60 at risk EG0016 events4 affected33 at risk EG00210 events8 affected57 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected60 at risk EG0010 events0 affected33 at risk EG0020 events0 affected57 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected60 at risk EG0010 events0 affected33 at risk EG0023 events3 affected57 at risk
Flushing	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0007 events4 affected60 at risk EG0013 events2 affected33 at risk EG0021 events1 affected57 at risk
Hypotension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected60 at risk EG0012 events2 affected33 at risk EG0027 events6 affected57 at risk

ID	Term
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D007938	Leukemia
D012008	Recurrence
D008228	Lymphoma, Non-Hodgkin

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008223	Lymphoma

ID	Term
D000069283	Rituximab
D000069461	Bendamustine Hydrochloride
C000609745	inebilizumab

ID	Term
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
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
BG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
BG002	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
BG003	TOTAL	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Rituximab + Bendamustine	Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.	19	60	58	60
EG001	MEDI-551 2 mg/kg + Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.	16	33	31	33
EG002	MEDI-551 4 mg/kg + Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.	19	57	54	57