Trial Outcomes & Findings for A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE) (NCT NCT00719472)

NCT ID: NCT00719472

Last Updated: 2017-05-15

Results Overview

The percentage of patients who developed Grade 3 or 4 IRRs resulting from faster infusion of rituximab at Cycle 2 was assessed in patients who had previously received rituximab at the standard infusion rate without experiencing a Grade 3 or 4 IRR at Cycle 1. IRRs were a predefined list of Medical Dictionary for Regulatory Activities (MedDRA) terms for infusion-related adverse events occurring on the day of and/or the day after rituximab infusion. The list of IRR terms was compiled based on IRRs observed in the present and previous studies in which rituximab was infused at the standard rate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

451 participants

Primary outcome timeframe

Days 1 and 2 of Cycle 2

Results posted on

2017-05-15

Participant Flow

Of 451 enrolled patients, 26 withdrew before receiving treatment and are not included in the Baseline Characteristics nor any of the Outcome Measures.

Participant milestones

Participant milestones
Measure	Rituximab 375 mg/m^2 Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Enrolled in Study STARTED	451
Enrolled in Study COMPLETED	425
Enrolled in Study NOT COMPLETED	26
Received Cycle 1 Treatment STARTED	425
Received Cycle 1 Treatment COMPLETED	372
Received Cycle 1 Treatment NOT COMPLETED	53
Received Cycle 2 Treatment STARTED	372
Received Cycle 2 Treatment COMPLETED	304
Received Cycle 2 Treatment NOT COMPLETED	68

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab 375 mg/m^2 Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Enrolled in Study Physician decision to withdraw patient	1
Enrolled in Study Subject decision to withdraw	8
Enrolled in Study Various Reasons	17
Received Cycle 1 Treatment Adverse Event	8
Received Cycle 1 Treatment Death	5
Received Cycle 1 Treatment Eligibility criteria for Cycle 2 not met	11
Received Cycle 1 Treatment Physician decision to withdraw patient	7
Received Cycle 1 Treatment Subject decision to withdraw	9
Received Cycle 1 Treatment Various Reasons	13
Received Cycle 2 Treatment Adverse Event	12
Received Cycle 2 Treatment Death	6
Received Cycle 2 Treatment Disease progression	3
Received Cycle 2 Treatment Lost to Follow-up	3
Received Cycle 2 Treatment Physician decision to withdraw patient	13
Received Cycle 2 Treatment Subject decision to withdraw	6
Received Cycle 2 Treatment Various Reasons	25

Baseline Characteristics

A Study of Rituximab Alternative Dosing Rate in Patients With Previously Untreated Diffuse Large B-cell or Follicular Non-Hodgkin's Lymphoma (RATE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab 375 mg/m^2 n=425 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Age, Continuous	62.7 years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	191 Participants n=5 Participants
Sex: Female, Male Male	234 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 1 and 2 of Cycle 2

Population: Per-protocol evaluable population: All patients who received rituximab by faster infusion in Cycle 2 and who did not experience a Grade 3 or 4 infusion-related reaction during the rituximab infusion given at the standard rate during Cycle 1.

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=363 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Percentage of Patients Who Developed Grade 3 or 4 Infusion-related Reactions (IRR) Resulting From Faster Infusion of Rituximab During Days 1 and 2 of Cycle 2	1.1 Percentage of participants Interval 0.3 to 2.8

SECONDARY outcome

Timeframe: Cycle 1

Population: Intent-to-treat (ITT) population: All patients who received at least 1 dose of rituximab regardless of infusion rate.

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=425 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 1	91.8 Percentage of participants

SECONDARY outcome

Timeframe: Cycle 2 through Cycle 6 or 8 (end of study)

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=363 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Percentage of Patients Who Had an Adverse Event of Any Grade or Seriousness During Cycle 2 Through Cycle 6 or 8 (End of Study)	98.6 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 of each of Cycles 1 to 6 or 8

The median duration of the rituximab infusion on Day 1 of each cycle, including the duration of dose interruptions, is reported.

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=363 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 3 (n=344)	91 Minutes Interval 90.0 to 98.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 4 (n=329)	91 Minutes Interval 90.0 to 96.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 5 (n=312)	91 Minutes Interval 90.0 to 95.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 1 (n=362)	245 Minutes Interval 225.0 to 273.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 2 (n=363)	91 Minutes Interval 90.0 to 98.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 6 (n=303)	91 Minutes Interval 90.0 to 96.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 7 (n=59)	91 Minutes Interval 90.0 to 95.0
Duration of Rituximab Infusion Including Dose Interruption Times Cycle 8 (n=59)	91 Minutes Interval 90.0 to 95.0

SECONDARY outcome

Timeframe: Day 1 of Cycles 2 and either 6 or 8 (last cycle)

Population: Pharmacokinetic evaluable population: All patients who received at least 1 infusion of rituximab and had rituximab concentration data.

Serum samples for rituximab pharmacokinetic analysis were taken pre-dose (within 15 minutes before rituximab infusion) and post-dose (within 15 minutes after the end of the rituximab infusion) after the first faster infusion (Cycle 2) and after the last infusion (either Cycle 6 or 8). An enzyme-linked immunosorbent assay (ELISA) was used to measure rituximab levels in the serum samples.

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=335 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Maximum Serum Concentration (Cmax) of Rituximab Post-dose at the First Alternative Dosing Rate (Cycle 2) and the Last Cycle (Either Cycle 6 or 8) Cycle 2 (n=335)	228.0 µg/mL Standard Deviation 63.7
Maximum Serum Concentration (Cmax) of Rituximab Post-dose at the First Alternative Dosing Rate (Cycle 2) and the Last Cycle (Either Cycle 6 or 8) Cycle 6 (n=238)	275.0 µg/mL Standard Deviation 71.5
Maximum Serum Concentration (Cmax) of Rituximab Post-dose at the First Alternative Dosing Rate (Cycle 2) and the Last Cycle (Either Cycle 6 or 8) Cycle 8 (n=36)	299.0 µg/mL Standard Deviation 90.6

SECONDARY outcome

Timeframe: Day 1 of Cycle 2 and either Cycle 6 or 8 (last cycle)

Serum samples for measurement of CD19+ lymphocytes were taken pre-dose (within 15 minutes before rituximab infusion). CD19+ lymphocyte counts were measured by flow cytometry using a fluorescent-activated cell sorter (FACS).

Outcome measures

Outcome measures
Measure	Rituximab 375 mg/m^2 n=338 Participants Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle) Cycle 2 (n=338)	50.5 Percentage of participants 24
Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle) Cycle 6 (n=240)	68.3 Percentage of participants 4
Percentage of Patients Who Had Undetectable Levels of CD19+ Lymphocytes at Cycle 2 and Either Cycle 6 or 8 (Last Cycle) Cycle 8 (n=32)	87.5 Percentage of participants 0

Adverse Events

Rituximab 375 mg/m^2

Serious events: 107 serious events

Other events: 421 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab 375 mg/m^2 n=425 participants at risk Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Blood and lymphatic system disorders Febrile neutropenia	7.8% 33/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Neutropenia	2.4% 10/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Pancytopenia	1.6% 7/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Anaemia	1.2% 5/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Leukopenia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Thrombocytopenia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Cardiac arrest	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Ventricular tachycardia	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Cardiac failure congestive	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Atrial fibrillation	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Cardiomyopathy	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Cardiac disorders Acute myocardial infarction	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Abdominal pain	1.4% 6/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Nausea	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Vomiting	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Constipation	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Small intestinal obstruction	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Pancreatitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Colitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Diarrhoea	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Faecaloma	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Gastric perforation	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Gastritis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Intestinal mass	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Dysphagia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Haemorrhoids	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Small intestinal perforation	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Colonic obstruction	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Megacolon	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Stomatitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Pyrexia	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Chest pain	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Asthenia	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Hepatobiliary disorders Hepatic failure	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Hepatobiliary disorders Ischaemic hepatitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Pneumonia	1.6% 7/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Bronchitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Lung infection	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Sepsis	1.2% 5/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Device related sepsis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Fungal sepsis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Neutropenic sepsis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Septic shock	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Staphylococcal infection	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Staphylococcal sepsis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Pseudomonal sepsis	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Gastroenteritis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Cellulitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Mastitis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Meningitis aseptic	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Hepatitis B	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Herpes zoster	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Streptococcal bacteraemia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Urinary tract infection	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Injury, poisoning and procedural complications Fall	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Injury, poisoning and procedural complications Wound dehiscence	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Injury, poisoning and procedural complications Accidental overdose	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Dehydration	2.8% 12/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Failure to thrive	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Malnutrition	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Decreased appetite	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hypercalcaemia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hypoglycaemia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hypokalaemia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Muscular weakness	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Cerebrovascular accident	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Cerebral ischaemia	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Convulsion	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Psychiatric disorders Anxiety	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Renal and urinary disorders Renal failure	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Renal and urinary disorders Renal failure acute	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Deep vein thrombosis	0.71% 3/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Jugular vein thrombosis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Venous thrombosis limb	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Hypotension	0.47% 2/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Orthostatic hypotension	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Thrombosis	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Superior vena cava syndrome	0.24% 1/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.

Other adverse events

Other adverse events
Measure	Rituximab 375 mg/m^2 n=425 participants at risk Patients received 6 or 8 21-day cycles of CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) or CVP (cyclophosphamide, vincristine, prednisone) in combination with rituximab 375 mg/m\^2 administered by intravenous (IV) infusion on Day 1 of each cycle.
Blood and lymphatic system disorders Neutropenia	31.8% 135/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Anaemia	23.5% 100/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Thrombocytopenia	12.9% 55/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Blood and lymphatic system disorders Leukopenia	7.3% 31/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Nausea	47.5% 202/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Vomiting	16.2% 69/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Constipation	33.4% 142/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Diarrhoea	23.3% 99/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Abdominal pain	10.1% 43/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Dyspepsia	12.0% 51/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Stomatitis	8.0% 34/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Gastrointestinal disorders Dry mouth	8.7% 37/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Fatigue	53.4% 227/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Asthenia	11.1% 47/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Pain	7.1% 30/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Chest pain	5.4% 23/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Pyrexia	14.8% 63/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Chills	11.5% 49/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Oedema peripheral	10.4% 44/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
General disorders Mucosal inflammation	10.1% 43/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Upper respiratory tract infection	6.4% 27/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Infections and infestations Candidiasis	5.2% 22/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Investigations Weight decreased	7.8% 33/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Decreased appetite	16.9% 72/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Dehydration	8.5% 36/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hypokalaemia	6.8% 29/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hypomagnesaemia	6.1% 26/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Metabolism and nutrition disorders Hyperglycaemia	5.4% 23/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Back pain	13.2% 56/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 24/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Bone pain	9.6% 41/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Arthralgia	10.1% 43/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 30/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Neuropathy peripheral	23.3% 99/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Peripheral sensory neuropathy	8.7% 37/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Dysgeusia	13.6% 58/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Headache	17.6% 75/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Dizziness	13.9% 59/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Nervous system disorders Paraesthesia	7.8% 33/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Psychiatric disorders Insomnia	23.5% 100/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Psychiatric disorders Anxiety	9.9% 42/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Psychiatric disorders Depression	5.2% 22/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.7% 37/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.4% 57/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Respiratory, thoracic and mediastinal disorders Cough	15.3% 65/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Skin and subcutaneous tissue disorders Alopecia	39.8% 169/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Skin and subcutaneous tissue disorders Rash	10.6% 45/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.6% 24/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Skin and subcutaneous tissue disorders Pruritus	6.6% 28/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.
Vascular disorders Hypotension	6.1% 26/425 • Adverse events and serious adverse events were recorded from the start of study treatment until 30 days following the last administration of study treatment or at study discontinuation/early termination, whichever occurred earlier. Adverse events are reported for the intent-to-treat (ITT) population which included all patients who received at least 1 dose of rituximab, regardless of infusion rate.

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER