A Study to Compare Subcutaneous Versus Intravenous MabThe... | NCT01292603

NCT01292603

ID	Type	Description	Link
2010-021380-32	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
1	Experimental	Drug: Cyclophosphamide Drug: Fludarabine Drug: rituximab [MabThera]
2	Experimental	Drug: Cyclophosphamide Drug: Fludarabine Drug: rituximab [MabThera]
3	Experimental	Drug: Cyclophosphamide Drug: Fludarabine Drug: rituximab [MabThera]

Name	Type	Description	Arm Group Labels	Other Names
Cyclophosphamide	Drug	Days 1-3 or Days 1-5 of cycles 1-6	1 2 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab	Ctrough is defined as the trough or minimum serum concentration. Pharmacokinetic parameters for rituximab were assessed during Cycles 5 (IV rituximab) and 6 (SC rituximab). Rituximab pharmacokinetic (PK) data from Part 1 were integrated into a population PK model using parametric, nonlinear, mixed-effects modelling. Rituximab IV 500 mg/m^2 administered once every 4 weeks was compared to fixed doses of rituximab SC between 1400 mg and 1870 mg. The dose selection was performed on Ctrough concentrations at Cycle 5 (pre-dose Cycle 6). A test of the probability of success was applied to each of the 100 replicates, and the percentage of replicates with a positive test corresponded to the probability of success of the trial.	Pre-dose and post-dose (15 minutes to end of infusion) on Day 1 and on Days 2, 5, 11 and 15 of Cycle 5 and Pre-dose, Post-dose on Days 2, 3, 5,11, 15 and 29 of Cycle 6; Pre-dose was taken 2 hours prior rituximab dose
Part 2: Rituximab C Trough Levels at Cycle 5	Ctrough is defined as the trough or minimum serum concentration in a given cycle of treatment. The objective of Part 2 was to demonstrate the comparability of the observed Ctrough of rituximab SC 1600 mg and rituximab IV 500 mg/m2 at Cycle 5, as assessed by a non-inferiority test with a lower boundary of at least 0.8 for the 90% CI.	+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration

Secondary Outcomes

Measure	Description	Time Frame
Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6	AUC values were calculated by numerical integration using the linear trapezoidal rule. AUC levels were analyzed using the model below: Ln(AUC) = μ + τi + BlTLij + εij wherein, Ln is the natural log, μ denotes the overall mean effect, τi the effect in each treatment group, BlTLij the tumor load at baseline for each patient and εij a random error variable with normal distribution and mean 0. The treatment effect therein was based on a contrast statement in the model to calculate 90 % confidence intervals for ln(AUC SC)- ln(AUC IV).

Eligibility Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Fundaleu; Haematology		Buenos Aires		C1114AAN	Argentina
Cemic; Haematology

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26947201	Derived	Assouline S, Buccheri V, Delmer A, Gaidano G, Trneny M, Berthillon N, Brewster M, Catalani O, Li S, McIntyre C, Sayyed P, Badoux X. Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial. Lancet Haematol. 2016 Mar;3(3):e128-38. doi: 10.1016/S2352-3026(16)00004-1.
25900065

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: Rituximab SC 1400 Milligrams (mg)	Participant could have been enrolled any time during their treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 milligrams per square meter (mg/m^2) on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Part 1: Rituximab SC 1400 Milligrams (mg)	Participant could have been enrolled any time during their treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
BG001	Part 1: Rituximab SC 1600 mg	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
BG002	Part 1: Rituximab SC 1870 mg	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
BG003	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
BG004	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
BG005	Total	Total of all reporting groups

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

Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab

Ctrough is defined as the trough or minimum serum concentration. Pharmacokinetic parameters for rituximab were assessed during Cycles 5 (IV rituximab) and 6 (SC rituximab). Rituximab pharmacokinetic (PK) data from Part 1 were integrated into a population PK model using parametric, nonlinear, mixed-effects modelling. Rituximab IV 500 mg/m^2 administered once every 4 weeks was compared to fixed doses of rituximab SC between 1400 mg and 1870 mg. The dose selection was performed on Ctrough concentrations at Cycle 5 (pre-dose Cycle 6). A test of the probability of success was applied to each of the 100 replicates, and the percentage of replicates with a positive test corresponded to the probability of success of the trial.

Enrolled (non-randomized) Pharmacokinetic Evaluable Population (Part 1) included all participants from Part 1 who did not significantly violate the inclusion or exclusion criteria, deviate significantly from the protocol or have unavailable or incomplete data which could influence the pharmacokinetic analysis.

Posted

Number

Pre-dose and post-dose (15 minutes to end of infusion) on Day 1 and on Days 2, 5, 11 and 15 of Cycle 5 and Pre-dose, Post-dose on Days 2, 3, 5,11, 15 and 29 of Cycle 6; Pre-dose was taken 2 hours prior rituximab dose

ID	Title	Description
OG000	Part 1: Rituximab SC	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400, 1600 or 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Units	Counts
Participants	OG00056

Title

Denominators

Categories

Title	Measurements
	OG0001600

Primary

Part 2: Rituximab C Trough Levels at Cycle 5

Ctrough is defined as the trough or minimum serum concentration in a given cycle of treatment. The objective of Part 2 was to demonstrate the comparability of the observed Ctrough of rituximab SC 1600 mg and rituximab IV 500 mg/m2 at Cycle 5, as assessed by a non-inferiority test with a lower boundary of at least 0.8 for the 90% CI.

Only participants who entered Part 2 of the study and had pharmacokinetic (PK) data available were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6

AUC values were calculated by numerical integration using the linear trapezoidal rule. AUC levels were analyzed using the model below: Ln(AUC) = μ + τi + BlTLij + εij wherein, Ln is the natural log, μ denotes the overall mean effect, τi the effect in each treatment group, BlTLij the tumor load at baseline for each patient and εij a random error variable with normal distribution and mean 0. The treatment effect therein was based on a contrast statement in the model to calculate 90 % confidence intervals for ln(AUC SC)- ln(AUC IV).

Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*day/mL

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6

Cmax was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of rituximab in the blood samplings.

Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6

Multiple blood samples were obtained at pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab IV arm, and at pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab SC arm and time to peak plasma concentration of rituximab was determined.

Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

days

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Terminal Half-Life of Rituximab at Cycle 6

The terminal half-life (t1/2) of rituximab is defined as the time required for the plasma concentration of rituximab to reach half of its original concentration.

Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

days

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration

In part 1 of the trial, upon completion of dosing in cycle 6, participants and their treating nurses were asked whether they have a preference of dosing route, IV vs SC

All participants in Part 1 were included in this analysis including 8 participants that did not receive SC rituximab.

Posted

Number

percentage of participants or nurses

Days 4 to 5 in Cycle 6

ID	Title	Description
OG000	Part 1: Rituximab SC 1400 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 1: Rituximab SC 1600 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV

Physicians and nurses who administered rituximab were asked to answer the following question: " If used in routine practice, on average, how much staff time could be saved with each administration of rituximab SC as compared to rituximab IV? (Please do not consider the time needed for the first IV administration, consider only the subsequent ones)". The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.

All the physicians and nurses who responded to the questionnaire were included in the analysis.

Posted

Number

percentage of participants in the survey

Days 4-5 in Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV

Physicians and nurses who administered rituximab were asked to answer the following question: "Which formulation of rituximab (SC or IV) do you think is more convenient?" with pre-specified responses as below. Percentage of participants with specified answers were reported. The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.

All the physicians and nurses who responded to the questionnaire were included in the analysis.

Posted

Number

percentage of participants in the survey

Days 4-5 in Cycle 6

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 1: Percentage of Participants With Anti-Rituximab Antibodies

Blood samples for the assessment of antibodies against rituximab (HACAs) were drawn pre-dose at Cycle 5 and Cycle 6 in Part 1 and at each follow up visit until 24 months after the last dose.

Safety Analysis Population (SAP): all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. This included 8 participants that did not receive SC rituximab. n = number of participants analyzed.

Posted

Number

percentage of participants

Predose at Cycles 5 and 6 and at each follow up visit until 24 months after the last dose

ID	Title	Description
OG000	Part 1: Rituximab SC	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400, 1600 or 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Units	Counts
Participants

Secondary

Part 2: Percentage of Participants With Anti-Rituximab Antibodies

In Part 2, samples for the HACA assay were collected at each treatment cycle prior to the administration of rituximab and at each follow-up visit until 24 months after the last dose of rituximab.

SAP; n = number of participants analyzed for the specific parameter.

Posted

Number

percentage of participants

Day 0 of Cycle 1 and Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and at each follow-up visit until 24 months after the last dose of rituximab.

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Part 1 SAP; n = number of participants analyzed at the specified visit.

Posted

Median

Full Range

cells per microliter (cells/μL)

Day 1 of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15,18, 21 and 24

ID	Title	Description
OG000	Part 1: Rituximab SC 1400 Milligrams (mg)	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 1: Rituximab SC 1600 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 1: Percentage of Participants With Total B-Cell Depletion by Visit

Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL.

Part 1 SAP; n = number of participants analyzed at the specified visit.

Posted

Number

percentage of participants

Day 1 pre-dose of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15, 18, 21 and 24

ID	Title	Description
OG000	Part 1: Rituximab SC 1400 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 1: Rituximab SC 1600 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Total CD19+ B-Cell Counts by Visit

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Part 2 SAP; n = number of participants analyzed at the specified visit.

Posted

Median

Full Range

cells/μL

Cycle 1 pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 pre-dose in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Secondary

Part 2: Percentage of Participants With Total B-Cell Depletion by Visit

Part 2 SAP; n= number of participants analyzed at the specified visit.

Posted

Number

percentage of participants

Cycle 1 Pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit

ID	Title	Description
OG000	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
OG001	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: Rituximab SC 1400 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	5	16	13	16
EG001	Part 1: Rituximab SC 1600 mg	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	8	17	16	17
EG002	Part 1: Rituximab SC 1870 mg	PParticipant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	4	22	21	22
EG003	Part 1: Rituximab SC 1000 mg	One participant enrolled in the rituximab SC 1870 mg subcohort received 1000 mg rituximab SC during Cycle 6 in error. Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1000 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	1	1	1	1
EG004	Part 1: No SC Dose Received	These participants were withdrawn prior to SC treatment.	3	8	7	8
EG005	Part 2 : Rituximab IV 500 mg/m^2	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	35	89	80	89
EG006	Part 2: Rituximab SC 1600 mg	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	32	85	81	85

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0022 affected22 at risk EG0031 affected1 at risk EG004
Anaemia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Peumonia	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Pelvic Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Skin Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Adenocarcinoma Gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Brain Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Malignant Melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Metastases to Peritoneum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Pyrexia	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Death	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Drug Hypersensitivity	Immune system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Cardiac Failure	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Diabetic Retinal Oedema	Eye disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Wound Dehiscene	Injury, poisoning and procedural complications	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Tumor Lysis Syndrome	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Guillain- Barre Syndrome	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Haemolytic Anaemia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Neutropenic Colitis	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Localised Oedema	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hepatitis Toxic	Hepatobiliary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Lower Respiratory Tract Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Cellulitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hepatitis B	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Influenza	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Listeriosis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Lung Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Meningitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Meningitis Cryptococcal	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Oesophageal Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Progressive Multifocal Leukoencephalopathy	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Pulpitis Dental	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Tuberculosis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Wound Infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Meniscus Injury	Injury, poisoning and procedural complications	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Meralgia Paraesthetica	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Syncope	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Bronchitis Chronic	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Cystitis Haemorrhagic	Renal and urinary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Dermatitis Allergic	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Rash Maculo- Papular	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hypertension	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
ENTEROCOLITIS	Gastrointestinal disorders	MedDRA (20,1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BACTERIAL SEPSIS	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BARTHOLINITIS	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
BRONCHITIS	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
MYELODYSPLASTIC SYNDROME	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
PROSTATE CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
TACHYCARDIA	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
ANAL ULCER	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
MOUTH ULCERATION	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BRONCHOPULMONARY ASPERGILLOSIS	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
SEPTIC SHOCK	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
STAPHYLOCOCCAL INFECTION	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
VARICELLA ZOSTER VIRUS INFECTION	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BASAL CELL CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BOWEN'S DISEASE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
BREAST CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
DIFFUSE LARGE B-CELL LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
HODGKIN'S DISEASE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
METASTATIC SQUAMOUS CELL CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
PAPILLARY THYROID CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
REFRACTORY ANAEMIA WITH AN EXCESS OF BLASTS	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MeDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
SQUAMOUS CELL CARCINOMA OF SKIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
THYROID CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
ENCEPHALITIS AUTOIMMUNE	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0007 affected16 at risk EG0018 affected17 at risk EG0029 affected22 at risk EG0031 affected1 at risk EG0043 affected8 at risk EG00551 affected89 at risk EG00654 affected85 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0003 affected16 at risk EG0016 affected17 at risk EG0020 affected22 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0012 affected17 at risk EG0021 affected22 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0013 affected17 at risk EG0022 affected22 at risk EG003
Agranulocytosis	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Granulocytopenia	Blood and lymphatic system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0016 affected17 at risk EG0024 affected22 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0012 affected17 at risk EG0027 affected22 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0014 affected17 at risk EG0023 affected22 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0022 affected22 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Gingival erythema	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Pyrexia	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0015 affected17 at risk EG0021 affected22 at risk EG003
Chills	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0013 affected17 at risk EG0021 affected22 at risk EG003
Injection site pain	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0013 affected17 at risk EG0023 affected22 at risk EG003
Injection site erythema	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0024 affected22 at risk EG003
Asthenia	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0012 affected17 at risk EG0021 affected22 at risk EG003
Fatigue	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0013 affected17 at risk EG0020 affected22 at risk EG003
Chest discomfort	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Chest pain	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Feeling hot	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Injection site discolouration	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Injection site swelling	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Oedema Peripheral	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Sinusitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0024 affected22 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0023 affected22 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Bronchitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Rhinitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Fungal infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Giardiasis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Laryngitis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Vulvovaginitis trichomonal	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0023 affected22 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0013 affected17 at risk EG0020 affected22 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0022 affected22 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0022 affected22 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Panniculitis	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Pityriasis	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Headache	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0002 affected16 at risk EG0013 affected17 at risk EG0023 affected22 at risk EG003
Dizziness	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0012 affected17 at risk EG0020 affected22 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Weight decreased	Investigations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Immunoglobulins decreased	Investigations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Serum ferritin decreased	Investigations	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Mycosis fungoides	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Renal oncocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Diplopia	Eye disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0021 affected22 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Palpitations	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hypotension	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Thrombophlebitis	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
DYSCHEZIA	Gastrointestinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
GAIT DISTURBANCE	General disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Pneumonia	Infections and infestations	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0022 affected22 at risk EG003
Type 2 Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0021 affected22 at risk EG003
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0022 affected22 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0011 affected17 at risk EG0020 affected22 at risk EG003
Hot Flush	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Peripheral Venous Disease	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0001 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003
Hypertension	Vascular disorders	MedDRA (20.1)	Non-systematic Assessment	EG0000 affected16 at risk EG0010 affected17 at risk EG0020 affected22 at risk EG003

Ancestor Terms

ID	Term
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

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
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

ID	Term
D003520	Cyclophosphamide
C024352	fludarabine
D000069283	Rituximab