Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plu... | NCT02592876

Label	Type	Description	Intervention Names
19A+RICE	Experimental	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide	Drug: denintuzumab mafodotin Drug: rituximab Drug: ifosfamide Drug: carboplatin Drug: etoposide
RICE	Active Comparator	Rituximab, ifosfamide, carboplatin, and etoposide	Drug: rituximab Drug: ifosfamide Drug: carboplatin Drug: etoposide

Name	Type	Description	Arm Group Labels	Other Names
denintuzumab mafodotin	Drug	Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.	19A+RICE

Measure	Description	Time Frame
Complete Remission Rate Per Independent Review Facility	Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.	Up to 4 months

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. AE severity and seriousness are assessed independently. 'Severity' characterizes the intensity of an AE and is graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. An AE is considered 'serious' if it is life-threatening, fatal, requires hospitalization, or is otherwise considered to be medically significant.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically confirmed diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL; including de novo and transformed DLBCL) or Grade 3b follicular lymphoma
Available representative tissue from the most recent biopsy after the last therapy; if such tissue is not available, a fresh biopsy must be obtained
Received only frontline CD20-directed immunotherapy with anthracycline- or anthracenedione-based multi-agent chemotherapy. Monotherapy rituximab or other CD20-directed immunotherapy as maintenance therapy prior to frontline chemotherapy, and radiotherapy in a limited field or as part of the frontline treatment plan are permitted.
Achieved a response of stable disease, partial response, or complete response following the last cycle of frontline treatment. In addition, patients must have relapsed less than or equal to 6 months from the completion of frontline therapy at the time of initial dosing in this clinical trial.
Considered eligible for high-dose chemotherapy followed by autologous stem cell transplant (ASCT)
Fluorodeoxyglucose (FDG)-avid disease by positive emission tomography (PET), and measurable disease greater than 1.5 cm in diameter
Eastern Cooperative Oncology Group (ECOG) performance less than or equal to 2
Adequate kidney and hematologic function assessed from baseline laboratory data

Exclusion Criteria:

Previous history of indolent lymphoma treated with more than 1 multi-agent chemotherapy regimen or previous cancer therapy for recurrent DLBCL or Grade 3b follicular lymphoma
History of autologous or allogeneic stem cell transplant
History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 1 year
History of progressive multifocal leukoencephalopathy (PML)
Cerebral/meningeal disease related to the underlying malignancy that has not been definitively treated
Known urinary tract obstruction
Patients with the following ocular conditions: corneal disorders, monocular vision (i.e., best corrected visual acuity greater than or equal to 20/200 in one eye), or active ocular disorders requiring treatment

Name	Affiliation	Role
Juan Pinelli, PA-C, MMSc	Seagen Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Arkansas for Medical Sciences		Little Rock	Arkansas	72205	United States
City of Hope National Medical Center

ID	Title	Description
FG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 28, 2017	Apr 18, 2019

Arm/Group Information

ID	Title	Description
BG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
BG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
BG002	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

Complete Remission Rate Per Independent Review Facility

Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Count of Participants

Participants

Up to 4 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Units	Counts
Participants	OG00040 OG00140

Title

Denominators

Categories

Title	Measurements
	OG00018 OG00125

Secondary

Number of Participants With Adverse Events (AEs)

Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. AE severity and seriousness are assessed independently. 'Severity' characterizes the intensity of an AE and is graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. An AE is considered 'serious' if it is life-threatening, fatal, requires hospitalization, or is otherwise considered to be medically significant.

The safety analysis set includes all patients who received any amount of denintuzumab mafodotin or any component of RICE. Treatment group is determined using the actual treatment arm received, regardless of the randomization treatment assignment.

Posted

Count of Participants

Participants

Up to 4 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Number of Participants With Laboratory Abnormalities

Number of participants who experienced a maximum post-baseline laboratory toxicity of Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03).

Posted

Count of Participants

Participants

Up to 4 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Objective Response Rate (ORR)

ORR is defined as the proportion of patients with complete remission (CR) or partial remission (PR) per independent review facility (IRF) at the end of treatment.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Count of Participants

Participants

Up to 4 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Duration of Complete Response (CR)

Defined as the time from the start of the first radiographic documentation of CR per investigator to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Median

Inter-Quartile Range

months

Up to 27.9 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Duration of Objective Response (OR)

Duration of OR is defined as the time from the start of the first radiographic documentation of OR per investigator to the first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.

Posted

Median

Inter-Quartile Range

months

Up to 27.9 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Progression-free Survival (PFS)

PFS is defined as the time from randomization to first documentation of disease progression per investigator, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Median

Inter-Quartile Range

months

Up to 30 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Overall Survival (OS)

OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Median

Inter-Quartile Range

months

Up to 30 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization

Defined as the number of patients who are able to adequately mobilize PBSC per investigator assessment on or after completion of study treatment, prior to subsequent anticancer therapy.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Count of Participants

Participants

Up to 30 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Secondary

Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)

Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy.

The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.

Posted

Count of Participants

Participants

Up to 30 months

ID	Title	Description
OG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
OG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	RICE	Rituximab, ifosfamide, carboplatin, and etoposide rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles	6	40	13	40	40	40
EG001	19A+RICE	Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles. rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles	9	40	19	40	40	40

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0013 affected40 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG0006 affected40 at risk EG0018 affected40 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0011 affected40 at risk
Tachycardia	Cardiac disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Gastritis	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Intestinal fistula	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Pyrexia	General disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0011 affected40 at risk
External ear cellulitis	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Lung infection	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Otitis externa	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Pneumonia	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Rhinovirus infection	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Sepsis	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Septic shock	Infections and infestations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Alanine aminotransferase increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Hepatic enzyme increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Platelet count decreased	Investigations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0013 affected40 at risk
White blood cell count decreased	Investigations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0012 affected40 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Headache	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Neurotoxicity	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Syncope	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Mediastinal mass	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Hypotension	Vascular disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk
Orthostatic hypotension	Vascular disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0011 affected40 at risk
Vena cava thrombosis	Vascular disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0010 affected40 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG00023 affected40 at risk EG00119 affected40 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0019 affected40 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v18.0	Systematic Assessment	EG00015 affected40 at risk EG00123 affected40 at risk
Dry eye	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0004 affected40 at risk EG00110 affected40 at risk
Foreign body sensation in eyes	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0014 affected40 at risk
Keratitis	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0014 affected40 at risk
Keratopathy	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG00127 affected40 at risk
Photophobia	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0018 affected40 at risk
Vision blurred	Eye disorders	MedDRA v18.0	Systematic Assessment	EG0005 affected40 at risk EG00126 affected40 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0015 affected40 at risk
Constipation	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG00011 affected40 at risk EG00112 affected40 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0005 affected40 at risk EG0019 affected40 at risk
Dry mouth	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0011 affected40 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0012 affected40 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0011 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG00025 affected40 at risk EG00126 affected40 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0012 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA v18.0	Systematic Assessment	EG00011 affected40 at risk EG00112 affected40 at risk
Asthenia	General disorders	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0013 affected40 at risk
Chills	General disorders	MedDRA v18.0	Systematic Assessment	EG0005 affected40 at risk EG0015 affected40 at risk
Fatigue	General disorders	MedDRA v18.0	Systematic Assessment	EG00021 affected40 at risk EG00119 affected40 at risk
Oedema peripheral	General disorders	MedDRA v18.0	Systematic Assessment	EG0007 affected40 at risk EG0015 affected40 at risk
Pyrexia	General disorders	MedDRA v18.0	Systematic Assessment	EG0004 affected40 at risk EG0014 affected40 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0013 affected40 at risk
Alanine aminotransferase increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0012 affected40 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0013 affected40 at risk
Blood creatinine increased	Investigations	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0011 affected40 at risk
Platelet count decreased	Investigations	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0016 affected40 at risk
Weight decreased	Investigations	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0012 affected40 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0008 affected40 at risk EG0017 affected40 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0013 affected40 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0013 affected40 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0006 affected40 at risk EG0017 affected40 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0008 affected40 at risk EG0017 affected40 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0013 affected40 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0013 affected40 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0013 affected40 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA v18.0	Systematic Assessment	EG0004 affected40 at risk EG0010 affected40 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v18.0	Systematic Assessment	EG0001 affected40 at risk EG0013 affected40 at risk
Dizziness	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0005 affected40 at risk EG0016 affected40 at risk
Dysgeusia	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0012 affected40 at risk
Headache	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0007 affected40 at risk EG0019 affected40 at risk
Paraesthesia	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0000 affected40 at risk EG0014 affected40 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0004 affected40 at risk EG0010 affected40 at risk
Syncope	Nervous system disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0012 affected40 at risk
Insomnia	Psychiatric disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0016 affected40 at risk
Dysuria	Renal and urinary disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0011 affected40 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0016 affected40 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0007 affected40 at risk EG0013 affected40 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0003 affected40 at risk EG0014 affected40 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA v18.0	Systematic Assessment	EG0004 affected40 at risk EG0016 affected40 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA v18.0	Systematic Assessment	EG0005 affected40 at risk EG0017 affected40 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0013 affected40 at risk
Hypotension	Vascular disorders	MedDRA v18.0	Systematic Assessment	EG0002 affected40 at risk EG0012 affected40 at risk

ID	Term
D016393	Lymphoma, B-Cell
D016403	Lymphoma, Large B-Cell, Diffuse
D008223	Lymphoma
D008224	Lymphoma, Follicular
D006402	Hematologic Diseases
D007154	Immune System Diseases
D007160	Immunoproliferative Disorders
D008206	Lymphatic Diseases
D008228	Lymphoma, Non-Hodgkin
D009369	Neoplasms
D009370	Neoplasms by Histologic Type

ID	Term
D008232	Lymphoproliferative Disorders
D006425	Hemic and Lymphatic Diseases

ID	Term
D000069283	Rituximab
D007069	Ifosfamide
D016190	Carboplatin
D005047	Etoposide

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D003520	Cyclophosphamide
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D010078	Oxazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D056831	Coordination Complexes
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates