FCR Versus FC Alone in the Treatment of Chronic Lymphocyt... | NCT00090051

NCT00090051

ID	Type	Description	Link
BO17072

Status Module

Name	Class
Biogen	INDUSTRY
Genentech, Inc.	INDUSTRY

Oversight Module

Label	Type	Description	Intervention Names
Fludarabine+Cyclophosphamide (FC)	Active Comparator		Drug: Fludarabine Phosphate Drug: Cyclophosphamide
Fludarabine+Cyclophosphamide+Rituximab (FCR)	Experimental		Drug: Rituximab Drug: Fludarabine Phosphate Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
Rituximab	Drug	Intravenous repeating dose	Fludarabine+Cyclophosphamide+Rituximab (FCR)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)	Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause, whichever came first. Patients without a PFS event were censored at their last tumor assessment date.	Mean observation time at time of analysis was approximately 26 months
Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC)	Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause (PFS events), whichever came first. Patients without a PFS event were censored at their last tumor assessment date.	Mean observation time at time of analysis was approximately 26 months
Final Analysis: Time to Progression-Free Survival Event	Time to progression-free survival (PFS) event was defined as the time between randomization and the date of first documented PFS event: disease progression, relapse or death by any cause, whichever came first.	Median observation time was approximately 5 years

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival was determined from the date of randomization to the date of death irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.	Mean observation time at time of analysis was approximately 26 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years
Established diagnosis of B-cell CLL by NCI Working Group criteria
≤1 previous line of chemotherapy
Expected survival >6 months
Acceptable hematologic status, liver function, renal function, and pulmonary function
Negative serum pregnancy test for both pre-menopausal women and for women who are < 2 years after the onset of menopause
Written informed consent

Exclusion Criteria:

Prior treatment with interferon, rituximab or other monoclonal antibody
Prior allogeneic bone marrow transplant (BMT) or autologous BMT or peripheral stem cell transplant (PBSCT) or patients who are considered to be candidates for allogeneic or autologous BMT or PSCT as assessed by their treating physician
Fertile men or women of childbearing potential not using adequate contraception
Severe Grade 3 or 4 non-hematological toxicity or prolonged (> 2 weeks) Grade 3 or 4 cytopenia on prior fludarabine or nucleoside analogue regimen
History of fludarabine-induced or clinically significant autoimmune cytopenia
History of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low-grade early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent.
Medical conditions requiring long term use (> 1 month) of systemic corticosteroids
Active bacterial, viral, or fungal infection requiring systemic therapy
Severe cardiac disease
Seizure disorders requiring anticonvulsant therapy
Severe chronic obstructive pulmonary disease with hypoxemia
Uncontrolled diabetes mellitus or hypertension
Transformation to aggressive B-cell malignancy.
Known infection with HIV, HCV, or hepatitis B
Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study
Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Facility	Status	City	State	ZIP	Country	Contacts
Uab Comprehensive Cancer Center		Birmingham	Alabama	35294-3300	United States
Pacific Coast Hematology/Oncology Medical Group

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24916506	Derived	Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G, Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T, Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, Larratt L, Rossiev VA, Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink AM, Hallek M, Bloehdorn J, Busch R, Benner A, Dohner H, Valente N, Wenger MK, Stilgenbauer S, Dornan D. PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia. Blood. 2014 Jul 17;124(3):420-5. doi: 10.1182/blood-2013-12-538975. Epub 2014 Jun 10.
23525797

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
FG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
BG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.
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

Progression-free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause, whichever came first. Patients without a PFS event were censored at their last tumor assessment date.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Median

95% Confidence Interval

Days

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units	Counts
Participants	OG000276 OG001276

Title

Denominators

Categories

Title	Measurements
	OG000660(556 to 735) OG001813(670 to 947)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis was that there was no difference between the 2 treatment groups. The alternative hypothesis was that progression-free survival was longer in the fludarabine+cyclophosphamide+rituximab (FCR) group.	Log Rank	non-stratified	0.0218		Hazard Ratio (HR)	0.76			2-Sided	95	0.60	0.96			The hazard ratio was estimated using Cox regression. The hazard ratio is relative to the fludarabine+cyclophosphamide(FC) group.		Superiority or Other

Secondary

Overall Survival (OS)

Overall survival was determined from the date of randomization to the date of death irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Median

95% Confidence Interval

Days

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Number of Participants With Overall Survival (OS) Events

Overall survival was determined from the date of randomization to the date of death (OS event) irrespective of cause. Patients who had not died at the time of the final analysis (clinical data cut-off) were censored at the date of the last contact.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Number

participants

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Event-free Survival (EFS)

Event free survival was measured from the day of randomization to the date of first documented PD, relapse after response, start of a new treatment or death from any cause. Patients without an EFS event were censored at their last tumor assessment date.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Median

95% Confidence Interval

Days

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Number of Participants With Event-free Survival (EFS) Events

Event free survival was measured from the day of randomization to the date of first documented Progressive Disease (PD), relapse after response, start of a new treatment or death from any cause (EFS events). Patients without an EFS event were censored at their last tumor assessment date.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Number

participants

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Primary

Number of Participants With Progression-free Survival (PFS) Events Assessed by the Independent Review Committee (IRC)

Progression-free survival as assessed by the IRC was defined as the time between randomization and the date of first documented disease progression, relapse after response, or death from any cause (PFS events), whichever came first. Patients without a PFS event were censored at their last tumor assessment date.

Intent-to-treat (ITT) population was comprised of all patients randomized in the study, irrespective of whether they received treatment or not.

Posted

Number

participants

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Disease-free Survival (DFS)

Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause. Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.

Intent-to-treat (ITT) population for patients with a Best Overall Response of Complete Response.

Posted

Median

95% Confidence Interval

Days

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Number of Participants With Disease-free Survival (DFS) Events

Disease free survival was defined for all patients with a best overall response (BOR) of Complete Response (CR) and measured the time from first documented CR in a sequence of consecutive CRs until documented disease progression, relapse or death from any cause (DFS events). Patients without a DFS event at the time of the analysis (clinical data cut-off) were censored at their last tumor assessment date.

Intent-to-treat (ITT) population with a Best Overall Response of Complete Response.

Posted

Number

participants

Mean observation time at time of analysis was approximately 26 months

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Primary

Final Analysis: Time to Progression-Free Survival Event

Time to progression-free survival (PFS) event was defined as the time between randomization and the date of first documented PFS event: disease progression, relapse or death by any cause, whichever came first.

Participants from the Intent-to-treat population, all randomized participants, who experienced a PFS event. Participants who did not have a PFS event at the time of the final analysis were censored at the date of the last contact.

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Final Analysis: Time to Overall Survival Event

Overall survival (OS) was determined from the date of randomization to the date of death (OS event) irrespective of cause.

The analysis included only those participants from the Intent-to-treat population,all randomized participants, who died. Participants who had not died at the time of the final analysis were censored at the date of the last contact.

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units

Secondary

Final Analysis: Time to Event-Free Survival Event

Event free survival (EFS) was defined as the time from the day of randomization to the date of first EFS event: documented disease progression, relapse after response, start of a new treatment or death from any cause.

Participants from the Intent-to-treat population, all randomized participants, who had an EFS event. Participants who did not have an ESF event at the time of the final analysis were censored at the date of the last contact.

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Secondary

Final Analysis: Percentage of Participants With Complete Response

Complete response was defined as the disappearance of all signs of cancer in response to treatment.

Intent-to-treat population included all randomized participants.

Posted

Number

Percentage of participants

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units	Counts
Participants

Secondary

Final Analysis: Time to Disease-Free Survival Event

Time to disease-free survival (DFS) event was defined as the time from first documented response until the first documented DFS event: disease progression, relapse or death from any cause.

Participants from the Intent-to-treat population, all randomized participants, with complete response. .

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units	Counts

Secondary

Final Analysis: Duration of Response

Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause.

Participants from the Intent-to-treat population, all randomized participants, with complete or partial response.

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units	Counts
Participants

Secondary

Final Analysis: Time to New Chronic Lymphocytic Leukemia (CLL) Treatment

Time to new CCL treatment was defined as the time from randomization to the first day of new treatment for CCL or death.

Participants from the Intent-to-treat population,all randomized participants, who started a new treatment for CLL or died.

Posted

Median

95% Confidence Interval

Days

Median observation time was approximately 5 years

ID	Title	Description
OG000	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.
OG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.

Units	Counts

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	Fludarabine+Cyclophosphamide (FC)	Fludarabine+cyclophosphamide (FC) intravenously for a total of 6 treatment cycles at intervals of 28 days. Fludarabine: 25 mg/m² IV on Days 1, 2, 3 for 6 cycles. Cyclophosphamide: 250 mg/m² IV on Days 1, 2, 3 for 6 cycles.			132	272	232	272
EG001	Fludarabine+Cyclophosphamide+Rituximab (FCR)	Rituximab and FC intravenously for a total of 6 treatment cycles at intervals of 28 days. Cycle 1: rituximab 375 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 2, 3, 4; cyclophosphamide 250 mg/m² IV on Days 2, 3, 4. Cycles 2-6: rituximab 500 mg/m² IV on Day 1; fludarabine 25 mg/m² IV on Days 1, 2, 3; cyclophosphamide 250 mg/m² IV on Days 1, 2, 3.			138	274	251	274

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Distension	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Acute Coronary Syndrome	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Acute Sinusitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Alpha Haemolytic Streptococcal Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00011 affected272 at risk EG0013 affected274 at risk
Anaemia Haemolytic Autoimmune	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0005 affected272 at risk EG0012 affected274 at risk
Angina Pectoris	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Angina Unstable	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Aplasia Pure Red Cell	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0012 affected274 at risk
Arrhythmia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Aspergillosis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Atrial Flutter	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Autoimmune Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Bacterial Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0010 affected274 at risk
Bicytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0010 affected274 at risk
Bladder Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Brain Abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Bronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0016 affected274 at risk
Bronchitis Viral	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Bronchopneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Bronchopulmonary Aspergillosis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Cardiac Arrest	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0011 affected274 at risk
Cardiopulmonary Failure	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Cellulitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Chest Wall Abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Chills	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Chondrosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Chronic Myelomonocytic Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Colitis Ulcerative	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Coronary Artery Insufficiency	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cytomegalovirus Gastrointestinal Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cytomegalovirus Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0011 affected274 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0012 affected274 at risk
Diverticulitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Endocarditis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Endocarditis Bacterial	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Evans Syndrome	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Febrile Bone Marrow Aplasia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0013 affected274 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00021 affected272 at risk EG00129 affected274 at risk
Fungal Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Furuncle	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Gastric Polyps	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Gastritis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Gastrointestinal Disorder	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
General Physical Health Deterioration	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Gingival Bleeding	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Haematotoxicity	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Haemolytic Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0012 affected274 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hepatic Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hepatitis B	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0015 affected274 at risk
Herpes Zoster	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0011 affected274 at risk
Hodgkin's Disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0011 affected274 at risk
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Klebsiella Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Laryngeal Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0013 affected274 at risk
Listeria Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Localised Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0010 affected274 at risk
Lung Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Lung Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0012 affected274 at risk
Lung Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Malaise	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Mesenteric Artery Embolism	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Metastases to Central Nervous System	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Metastatic Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Multi-Organ Failure	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Multiple Myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Mycobacterium Avium Complex Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Myelodysplastic Syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0012 affected274 at risk
Myocardial Infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0012 affected274 at risk
Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0007 affected272 at risk EG0018 affected274 at risk
Neutropenic Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Neutropenic Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0004 affected272 at risk EG0012 affected274 at risk
Oral Herpes	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Ovarian Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0005 affected272 at risk EG0015 affected274 at risk
Parainfluenzae Virus Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Paraneoplastic Pemphigus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Performance Status Decreased	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pneumocystis Jiroveci Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Pneumocystis Jiroveci Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0011 affected274 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00018 affected272 at risk EG00115 affected274 at risk
Pneumonia Herpes Viral	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pneumonia Primary Atypical	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Pseudomonal Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG0009 affected272 at risk EG00114 affected274 at risk
Rectal Abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Rectal Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0012 affected274 at risk
Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0014 affected274 at risk
Septic Shock	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0015 affected274 at risk
Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Squamous Cell Carcinoma of Skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0004 affected272 at risk EG0011 affected274 at risk
Staphylococcal Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Supraventricular Tachyarrhythmia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Tachycardia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0004 affected272 at risk EG0012 affected274 at risk
Tonsillitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Tuberculosis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Tumour Lysis Syndrome	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0011 affected274 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0012 affected274 at risk
Varicella	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Ventricular Arrhythmia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Viral Upper Respiratory Tract Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG0011 affected274 at risk
Vulval Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
West Nile Viral Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Wound Infection Staphylococcal	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cerebral Haemorrhage	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0010 affected274 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0010 affected274 at risk
Capsular Warning Syndrome	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cerebral Ischaemia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Cerebral Thrombosis	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Encephalopathy	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Nervous System Disorder	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Peripheral Motor Neuropathy	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG0011 affected274 at risk
Haematuria	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Renal Failure	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Calculus Ureteric	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cystitis Haemorrhagic	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Nephrotic Syndrome	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Aortic Aneurysm	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Embolism	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Femoral Artery Occlusion	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Haemorrhage	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Peripheral Embolism	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Night Sweats	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Palmar Erythema	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Rash Papular	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Stevens-Johnson Syndrome	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Toxic Epidermal Necrolysis	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Intervertebral Disc Disorder	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0012 affected274 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Dactylitis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Metatarsalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Soft Tissue Necrosis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cholecystitis Acute	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hepatitis Acute	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Cytokine Release Syndrome	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Drug Hypersensitivity	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hypersensitivity	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Open Wound	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Radius Fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Diabetes Mellitus Inadequate Control	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Metabolic Acidosis	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Haemoglobin Decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Oxygen Saturation Decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Hypothyroidism	Endocrine disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Infective Exacerbation of Chronic Obstructive Airways Disease	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Zygomycosis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Renal Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Thyroid Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected272 at risk EG0011 affected274 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Neurological Decompensation	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk
Acute Myeloid Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0011 affected274 at risk
Mycobacterial Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected272 at risk EG0010 affected274 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG000110 affected272 at risk EG001120 affected274 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00047 affected272 at risk EG00155 affected274 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00033 affected272 at risk EG00136 affected274 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00012 affected272 at risk EG00118 affected274 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00014 affected272 at risk EG00116 affected274 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00017 affected272 at risk EG00123 affected274 at risk
Bronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00015 affected272 at risk EG00113 affected274 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00015 affected272 at risk EG00112 affected274 at risk
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG00036 affected272 at risk EG00160 affected274 at risk
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG00045 affected272 at risk EG00145 affected274 at risk
Chills	General disorders	MedDRA 15.0	Systematic Assessment	EG0005 affected272 at risk EG00141 affected274 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	EG00030 affected272 at risk EG00128 affected274 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00096 affected272 at risk EG001110 affected274 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00050 affected272 at risk EG00157 affected274 at risk
Constipation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00030 affected272 at risk EG00140 affected274 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00032 affected272 at risk EG00131 affected274 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG00024 affected272 at risk EG00134 affected274 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00029 affected272 at risk EG00125 affected274 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected272 at risk EG00120 affected274 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG00019 affected272 at risk EG00123 affected274 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG00013 affected272 at risk EG00120 affected274 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected272 at risk EG00115 affected274 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00016 affected272 at risk EG00115 affected274 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG00011 affected272 at risk EG00120 affected274 at risk
Oedema peripheral	General disorders	MedDRA 15.0	Systematic Assessment	EG00011 affected272 at risk EG00114 affected274 at risk

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
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
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Term
D000069283	Rituximab
C042382	fludarabine phosphate
D003520	Cyclophosphamide