Bendamustine Hydrochloride in Combination With Rituximab... | NCT00891839

Label	Type	Description	Intervention Names
Bendamustine+Rituximab	Experimental	Patients receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).	Drug: Bendamustine Drug: Rituximab

Name	Type	Description	Arm Group Labels	Other Names
Bendamustine	Drug	Bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2 of each 28-day cycle. Dosage calculations for bendamustine are based on the patient's body surface area (BSA) at baseline, using actual weight for calculations. If there is a 10% change in a patient's weight during treatment, the most recent weight is used to recalculate the BSA. The new BSA is used in determining the doses to be administered in any subsequent cycles.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate (Complete Response + Partial Response) at the End of Cycles 3 and 6 Using the 2007 International Working Group Criteria	The International Working Group (IWG) criteria (Cheson et al 2007) for a complete response is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed. 95% CIs are calculated using binomial exact method.	Month 3 (end of cycle 3), Month 6 (end of cycle 6)

Secondary Outcomes

Measure	Description	Time Frame
Kaplan-Meier Estimate for Duration of Response	Duration of response is defined as the time between the date of the first response to date of progression or death. Response is determined on the basis of the 2007 IWG criteria. A complete response is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

histopathologically confirmed diagnosis of typical or atypical mantle cell lymphoma, except for blastoid type.
documented relapsed/refractory mantle cell lymphoma.
CD20 positive B cells in the lymph node biopsy or other lymphoma pathology specimen.
adequate hematologic function according to specific trial parameters.
bidimensionally measurable disease with at least 1 lesion measuring 2.0 cm or more in a single dimension, or the patient is in the leukemic phase of the disease.
patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
patient has an estimated life expectancy of at least 3 months.
women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of study drug treatment and for 30 days after participation in the treatment period.

Exclusion Criteria:

has received more than 3 previous standard chemotherapy regimens.
has the blastoid subtype of mantle cell lymphoma.
documented history of central nervous system (CNS) lymphomatous involvement.
a history of previous high-dose chemotherapy with allogeneic stem cell transplantation (history of autologous stem cell transplantation is allowed).
previous treatment with bendamustine.
has an active malignancy other than MCL, or has had a malignancy other than MCL within the past 3 years, except for controlled prostate cancer without evidence of bone metastases, localized bladder cancer, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer.
has New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months.
has serum creatinine of more than 2.0 mg/dL or creatinine clearance of less than 30 mL/min based on the Cockcroft-Gault method or from a 24-hour urine collection.
does not have adequate hepatic organ function as evidenced by specific trial parameters.
has known human immunodeficiency virus (HIV) infection.
has active hepatitis B infection. Hepatitis B surface antigen must be tested.
a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
has received corticosteroids within 28 days of study entry unless chronically administered (prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications.
any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to participate in or complete this study.
any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.
patient has received other investigational agent(s) within 28 days of study entry.
patient has received chemotherapy within the prior 28 days.
patient has a known hypersensitivity to bendamustine, mannitol, or rituximab.

Name	Affiliation	Role
Sponsor's Medical Expert	Cephalon	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 11		Fountain Valley	California		United States
Teva Investigational Site 2

ID	Title	Description
FG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

ID	Title	Description
BG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	BG00045

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00069.5± 8.02

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00013
Male	BG00032

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002
Not Hispanic or Latino	BG00043

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG0001

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00080.3± 13.59

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000172.7± 9.87

Body Surface Area (BSA)

Mean

Standard Deviation

m^2

Title

Denominators

Categories

Title	Measurements
	BG0001.9± 0.20

Ann Arbor Staging System of Lymphoma

Stage I indicates that the cancer is located in a single region.
Stage II indicates that the cancer is located in two separate regions, and that both affected areas are confined to one side of the diaphragm.
Stage III indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs

Number

participants

Title

Denominators

Categories

Stage I

Title	Measurements
	BG0000

Stage II

B-Symptoms

The presence of B symptoms is a marker for more advanced disease with systemic, rather than merely local, involvement.

B symptoms include:

Fever greater than 38 °C. Pel-Ebstein fever, the classic intermittent fever associated with Hodgkin disease, occurs at variable intervals of days to weeks and lasts for 1-2 weeks before resolving. However, fever associated with lymphoma can follow virtually any pattern.
Drenching sweats, especially at night.
Unintentional weight loss of >10% of normal body weight over a period of 6 months or less.

Number

participants

Title

Denominators

Categories

Present

Title	Measurements
	BG0009

Absent

Title

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

Overall Response Rate (Complete Response + Partial Response) at the End of Cycles 3 and 6 Using the 2007 International Working Group Criteria

The International Working Group (IWG) criteria (Cheson et al 2007) for a complete response is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.

95% CIs are calculated using binomial exact method.

Safety population consisting of all participants treated with at least 1 dose of bendamustine HCL.

Posted

Number

95% Confidence Interval

percentage of participants

Month 3 (end of cycle 3), Month 6 (end of cycle 6)

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	OG00045

Title

Denominators

Categories

end of Cycle 3

Title	Measurements
	OG00071(55.7 to 83.6)

end of Cycle 6

Title	Measurements
	OG00082(68.0 to 92.0)

Secondary

Kaplan-Meier Estimate for Duration of Response

Duration of response is defined as the time between the date of the first response to date of progression or death. Response is determined on the basis of the 2007 IWG criteria. A complete response is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed.

Safety population of participants who had a response.

Posted

Median

95% Confidence Interval

months

Day 1 up to Month 43

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	OG000

Secondary

Kaplan-Meier Estimate for Progression-Free Survival

Progression-free survival is defined as the time from first exposure to study medication to disease progression or relapse, or death due to any cause. Progression is defined using the 2007 International Working Group criteria, as any new lesion or increase by at least 50% of previously involved sites from nadir.

Safety population

Posted

Median

95% Confidence Interval

months

Day 1 up to Month 45

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	OG000

Secondary

Kaplan-Meier Estimate for Overall Survival

Overall survival is defined as the time from first exposure to study medication to death, or to last date from adverse events, concomitant medications, vital signs, lost to follow-up, or last known alive, for overall survival censoring date.

Safety population

Posted

Median

95% Confidence Interval

months

Day 1 up to Month 57

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	OG000

Secondary

Shifts in Baseline to Post-Treatment in Positron Emission Tomography (PET)

Participants had a whole-body PET at baseline and at the end of cycle 6 or the end-of-treatment visit. Negative PET refers to PET results showing no abnormal lymph nodes; conversely, positive PET refers to PET results showing abnormal lymph nodes.

Safety population of participants with PET data

Posted

Number

participants

Baseline (Days -30 to 0), post treatment (up to Month 9, 30 days following completion of therapy)

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants	OG000

Secondary

Shifts in Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status

The ECOG scale is:

Grade 0: Fully active, able to carry on all pre-disease activities without restriction;
Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;
Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours;
Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours;
Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or Chair.

The shift table compares baseline ECOG scores to the ECOG scores as of the last treatment visit.

Safety population. One participant dropped out prior to obtaining a post-treatment ECOG evaluation.

Posted

Number

participants

Day 0 (baseline) up to Month 8

ID	Title	Description
OG000	Bendamustine+Rituximab	Participants receive bendamustine at 90 mg/m^2 intravenously (iv) on days 1 and 2, and 375 mg/m^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Myocardial infarction	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Infusion related reaction	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Pyrexia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Bronchitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Device related infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Pneumonia	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Toxoplasmosis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Urosepsis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Burkitt's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Sedation	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Confusional state	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 events2 affected45 at risk
Hallucination, auditory	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Hallucination, visual	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Mental status changes	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0002 events2 affected45 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0001 events1 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00014 events10 affected45 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00012 events9 affected45 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0009 events6 affected45 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00029 events21 affected45 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00021 events12 affected45 at risk
Tachycardia	Cardiac disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 events6 affected45 at risk
Vision blurred	Eye disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 events6 affected45 at risk
Constipation	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00032 events17 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00026 events16 affected45 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 events5 affected45 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Flatulence	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00061 events31 affected45 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00027 events16 affected45 at risk
Asthenia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 events5 affected45 at risk
Chest pain	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 events3 affected45 at risk
Chills	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00015 events7 affected45 at risk
Fatigue	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00036 events25 affected45 at risk
Infusion related reaction	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0008 events4 affected45 at risk
Mucosal inflammation	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 events4 affected45 at risk
Oedema peripheral	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00012 events7 affected45 at risk
Pyrexia	General disorders	MedDRA (15.0)	Non-systematic Assessment	EG00024 events13 affected45 at risk
Cytokine release syndrome	Immune system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00011 events5 affected45 at risk
Pneumonia	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Sinusitis	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0006 events6 affected45 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.0)	Non-systematic Assessment	EG0004 events4 affected45 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Neutrophil count decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Weight decreased	Investigations	MedDRA (15.0)	Non-systematic Assessment	EG00015 events14 affected45 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG00025 events19 affected45 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events4 affected45 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG00014 events9 affected45 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 events4 affected45 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events4 affected45 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG00010 events8 affected45 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 events4 affected45 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 events4 affected45 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Dizziness	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00018 events11 affected45 at risk
Dysgeusia	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events4 affected45 at risk
Headache	Nervous system disorders	MedDRA (15.0)	Non-systematic Assessment	EG00013 events8 affected45 at risk
Anxiety	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events3 affected45 at risk
Confusional state	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Insomnia	Psychiatric disorders	MedDRA (15.0)	Non-systematic Assessment	EG00011 events9 affected45 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00018 events12 affected45 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG00022 events13 affected45 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0007 events5 affected45 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events3 affected45 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0003 events3 affected45 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG0006 events6 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Non-systematic Assessment	EG00014 events6 affected45 at risk
Flushing	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0005 events4 affected45 at risk
Hypertension	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG0004 events3 affected45 at risk
Hypotension	Vascular disorders	MedDRA (15.0)	Non-systematic Assessment	EG00012 events9 affected45 at risk

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

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