Rituximab Plus Lenalidomide for Patients With Relapsed /... | NCT01938001

NCT01938001

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rituximab and Lenalidomide	Experimental	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days, up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.	Drug: Rituximab Drug: Lenalidomide
Rituximab and Placebo	Active Comparator	Participants received riituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up, to 12 cycles.	Drug: Rituximab Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rituximab	Drug	Rituximab 375mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5	Rituximab and Lenalidomide Rituximab and Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)	Progression-free survival (PFS) was defined as the time from date of randomization into the study to the first observation of documented disease progression or death due to any cause, whichever occurred first. PFS was based on the data from the IRC review using the modified 2007 International Working Group Response Criteria (IWGRC) using FDA censoring rules.	From randomization of study drug up to disease progression or death, which occurred first; up to the data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

Secondary Outcomes

Measure	Description	Time Frame
Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC	DCCR was defined as the percentage of participants with a best response of complete response (CR) that lasted no less than one year (≥ 48 weeks) during the study prior to administration of new anti-lymphoma therapy. A CR is defined as a complete disappearance of any disease-related symptoms and normalization of biochemical abnormalities.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years at the time of signing the informed consent document.
Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
Histologically confirmed marginal zone lymphoma or follicular lymphoma (grade 1, 2 or 3a; CD20+ by flow cytometry or histochemistry).
Previously treated with at least one prior systemic chemotherapy, immunotherapy or chemoimmunotherapy and have received at least 2 previous doses of rituximab.
Documented relapsed, refractory or progressive disease after treatment with systemic therapy and must not be rituximab-refractory.
Investigator considers rituximab monotherapy appropriate.
Bi-dimensionally measurable disease on cross sectional imaging by X-ray computed tomography (CT) or magnetic resonance imaging (MRI).
Need of treatment for relapsed, progressed or refractory disease as assessed by the investigator.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Adequate bone marrow function.
Willingness to follow study visit schedule, pregnancy precautions and other protocol requirements.

Exclusion Criteria:

Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma.
Subjects taking corticosteroids during the last week prior to study treatment, unless administered at a dose equivalent to < 20 mg/day prednisone or prednisolone.
Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks use of radioimmunotherapy within 6 months.
Known seropositive for or active viral infection with hepatitis B virus (HBV) or/and human immunodeficiency virus (HIV).
Known hepatitis C virus (HCV) positive with chronic HCV or active viral infection with HCV hepatitis requiring anti-viral medication (at time of randomization).
Life expectancy < 6 months.
Known sensitivity or allergy to murine products.
Prior history of malignancies, other than follicular or marginal zone lymphoma, unless the subject has been free of the disease for ≥ 5 years.
Prior use of lenalidomide.
Known allergy to thalidomide.
Neuropathy > Grade 1.
Presence or history of central nervous system involvement by lymphoma.
Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it.
Uncontrolled intercurrent illness.
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document.
Pregnant or lactating females.
Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mitchell Cancer Center, University of South Alabama		Mobile	Alabama	36604	United States
Arizona Center for Cancer Care

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30184451	Background	Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
30897038

Label	URL
BMS Clinical Trial Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 13, 2018	Jun 21, 2019

Arm/Group Information

ID	Title	Description
BG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
BG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.
BG002	Total	Total of all reporting groups

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
	BG00062.30± 11.227 BG00161.48± 11.160 BG00261.89± 11.186

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000103 BG00183 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00024 BG00120 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG000118 BG001115 BG002

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

Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)

Progression-free survival (PFS) was defined as the time from date of randomization into the study to the first observation of documented disease progression or death due to any cause, whichever occurred first. PFS was based on the data from the IRC review using the modified 2007 International Working Group Response Criteria (IWGRC) using FDA censoring rules.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Median

95% Confidence Interval

months

From randomization of study drug up to disease progression or death, which occurred first; up to the data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Units	Counts
Participants	OG000178 OG001180

Title

Denominators

Categories

Title	Measurements
	OG00039.4(22.9 to NA)NA =Not enough events had occurred at the time of the data cut-off date OG00114.1(11.4 to 16.7)

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		Log Rank	Stratified by 3 factors: previous rituximab treatment, time since last antilymphoma therapy (≤ 2, > 2 years), and disease histology (FL, MZL).	< 0.0001		Hazard Ratio (HR)	0.46			2-Sided	95	0.34	0.62			Hazard ratio and its confidence interval (CI) were estimated from Cox proportional hazard model adjusting for the stratification factors noted above.		Superiority

Secondary

Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC

DCCR was defined as the percentage of participants with a best response of complete response (CR) that lasted no less than one year (≥ 48 weeks) during the study prior to administration of new anti-lymphoma therapy. A CR is defined as a complete disappearance of any disease-related symptoms and normalization of biochemical abnormalities.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Number

95% Confidence Interval

Percentage of Participants

From first dose of investigational product (IP) to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomiade arm and 11.04 months in the rituximab/placebo arm

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Kaplan-Meier Estimate of Overall Survival (OS)

Overall survival was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

The ITT population is defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Median

95% Confidence Interval

Months

From date of randomization to death due to any cause (Average of 55.71 months and a maximum up to 95.2 months)

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC

Percentage of participants with an objective response is defined as having a response of at least a PR during the study without administration of new anti-lymphoma therapy. A complete response = a complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities; a partial response (PR) = 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Number

95% Confidence Interval

Percentage of Participants

From date of first dose to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.

Secondary

Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC

Percentage of participants with a best response of at CR during the study without administration of new anti-lymphoma therapy. A CR = Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Number

95% Confidence Interval

Percentage of Participants

From date of first dose up to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC

Duration of response (DOR) was defined as the time from initial response (at least PR) until documented progressive disease (PD) or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.

Participants who achieved an objective response in the ITT population.

Posted

Median

95% Confidence Interval

months

From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC

DOCR was defined as the time from initial CR until documented PD or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.

Participants who achieved a complete response in the ITT population.

Posted

Median

95% Confidence Interval

months

From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC

Event-free survival (EFS) was defined as the time from date of randomization to date of first documented progression, relapse, institution of new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy) or death from any cause. Responding participants and those who were lost to follow up were censored at their last tumor assessment date.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Median

95% Confidence Interval

months

From date of randomization to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)

Time to next anti-lymphoma treatment (TTNLT) was defined as the time from date of randomization to date of first documented administration of a new anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy or immunotherapy). The time to the next anti-lymphoma treatment was of special interest to the study.

The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.

Posted

Median

95% Confidence Interval

Months

From date of randomization to date of first documented administration of a new anti-lymphoma treatment (Average of 55.71 months and a maximum up to 95.2 months)

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
OG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

TEAEs include AEs that started or worsened between the date of the first dose and 28 days after the date of the last dose. A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death

The safety population was defined as all participants who have received at least one dose of study medication.

Posted

Count of Participants

Participants

From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)

ID	Title	Description
OG000	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.

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	Rituximab + Lenalidomide (R^2)	Participants received rituximab 375 mg/m^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but < 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.	27	178	45	176	170	176
EG001	Rituximab + Placebo	Participants received rituximab 375 mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up to 12 cycles.	47	180	25	180	158	180

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0002 affected176 at risk EG0010 affected180 at risk
Febrile neutropenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0005 affected176 at risk EG0010 affected180 at risk
Leukopenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Neutropenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0003 affected176 at risk EG0010 affected180 at risk
Pancytopenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Angina pectoris	Cardiac disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Arrhythmia	Cardiac disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Atrial fibrillation	Cardiac disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0012 affected180 at risk
Atrial flutter	Cardiac disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Cardiopulmonary failure	Cardiac disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Myocardial infarction	Cardiac disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Supraventricular tachycardia	Cardiac disorders	24.1	Systematic Assessment	EG0002 affected176 at risk EG0010 affected180 at risk
Vertigo	Ear and labyrinth disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Retinal detachment	Eye disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Diarrhoea	Gastrointestinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Faecaloma	Gastrointestinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Haemorrhagic erosive gastritis	Gastrointestinal disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Haemorrhoids	Gastrointestinal disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Volvulus	Gastrointestinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Asthenia	General disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Fatigue	General disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
General physical health deterioration	General disorders	24.1	Systematic Assessment	EG0002 affected176 at risk EG0011 affected180 at risk
Localised oedema	General disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Oedema peripheral	General disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0011 affected180 at risk
Pyrexia	General disorders	24.1	Systematic Assessment	EG0003 affected176 at risk EG0010 affected180 at risk
Cholecystitis	Hepatobiliary disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Cholelithiasis	Hepatobiliary disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Anaphylactic shock	Immune system disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Infusion related hypersensitivity reaction	Immune system disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Appendicitis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0011 affected180 at risk
Cellulitis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Diverticulitis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Gastroenteritis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Herpes zoster	Infections and infestations	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Neurosyphilis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Pneumonia	Infections and infestations	24.1	Systematic Assessment	EG0006 affected176 at risk EG0016 affected180 at risk
Pneumonia influenzal	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Pyelonephritis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Pyelonephritis acute	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Respiratory tract infection	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Sepsis	Infections and infestations	24.1	Systematic Assessment	EG0003 affected176 at risk EG0012 affected180 at risk
Septic shock	Infections and infestations	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Sialoadenitis	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Upper respiratory tract infection	Infections and infestations	24.1	Systematic Assessment	EG0000 affected176 at risk EG0012 affected180 at risk
Urinary tract infection	Infections and infestations	24.1	Systematic Assessment	EG0001 affected176 at risk EG0011 affected180 at risk
Fall	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Femur fracture	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Infusion related reaction	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Lower limb fracture	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Rib fracture	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Traumatic fracture	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Dehydration	Metabolism and nutrition disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Seronegative arthritis	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0002 affected176 at risk EG0010 affected180 at risk
Transitional cell cancer of the renal pelvis and ureter localised	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Cerebrovascular accident	Nervous system disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0011 affected180 at risk
Syncope	Nervous system disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0012 affected180 at risk
Transient ischaemic attack	Nervous system disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0012 affected180 at risk
Acute kidney injury	Renal and urinary disorders	24.1	Systematic Assessment	EG0002 affected176 at risk EG0010 affected180 at risk
Haematuria	Renal and urinary disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Renal colic	Renal and urinary disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Adnexal torsion	Reproductive system and breast disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0011 affected180 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0013 affected180 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0004 affected176 at risk EG0011 affected180 at risk
Pulmonary toxicity	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG0002 affected176 at risk EG0010 affected180 at risk
Pruritus	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Deep vein thrombosis	Vascular disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Lymphoedema	Vascular disorders	24.1	Systematic Assessment	EG0001 affected176 at risk EG0010 affected180 at risk
Peripheral arterial occlusive disease	Vascular disorders	24.1	Systematic Assessment	EG0000 affected176 at risk EG0011 affected180 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG00028 affected176 at risk EG0018 affected180 at risk
Leukopenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG00037 affected176 at risk EG00118 affected180 at risk
Lymphopenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG0008 affected176 at risk EG00114 affected180 at risk
Neutropenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG000103 affected176 at risk EG00140 affected180 at risk
Thrombocytopenia	Blood and lymphatic system disorders	24.1	Systematic Assessment	EG00026 affected176 at risk EG0019 affected180 at risk
Abdominal pain	Gastrointestinal disorders	24.1	Systematic Assessment	EG00022 affected176 at risk EG00116 affected180 at risk
Abdominal pain upper	Gastrointestinal disorders	24.1	Systematic Assessment	EG00011 affected176 at risk EG0017 affected180 at risk
Constipation	Gastrointestinal disorders	24.1	Systematic Assessment	EG00046 affected176 at risk EG00125 affected180 at risk
Diarrhoea	Gastrointestinal disorders	24.1	Systematic Assessment	EG00055 affected176 at risk EG00142 affected180 at risk
Dyspepsia	Gastrointestinal disorders	24.1	Systematic Assessment	EG00016 affected176 at risk EG0015 affected180 at risk
Nausea	Gastrointestinal disorders	24.1	Systematic Assessment	EG00021 affected176 at risk EG00123 affected180 at risk
Stomatitis	Gastrointestinal disorders	24.1	Systematic Assessment	EG0009 affected176 at risk EG0017 affected180 at risk
Vomiting	Gastrointestinal disorders	24.1	Systematic Assessment	EG00018 affected176 at risk EG00113 affected180 at risk
Asthenia	General disorders	24.1	Systematic Assessment	EG00024 affected176 at risk EG00118 affected180 at risk
Chills	General disorders	24.1	Systematic Assessment	EG00014 affected176 at risk EG0018 affected180 at risk
Fatigue	General disorders	24.1	Systematic Assessment	EG00038 affected176 at risk EG00133 affected180 at risk
Influenza like illness	General disorders	24.1	Systematic Assessment	EG0009 affected176 at risk EG0017 affected180 at risk
Malaise	General disorders	24.1	Systematic Assessment	EG00013 affected176 at risk EG00110 affected180 at risk
Oedema peripheral	General disorders	24.1	Systematic Assessment	EG00024 affected176 at risk EG00115 affected180 at risk
Pyrexia	General disorders	24.1	Systematic Assessment	EG00035 affected176 at risk EG00127 affected180 at risk
Influenza	Infections and infestations	24.1	Systematic Assessment	EG00017 affected176 at risk EG0018 affected180 at risk
Nasopharyngitis	Infections and infestations	24.1	Systematic Assessment	EG00013 affected176 at risk EG00118 affected180 at risk
Pneumonia	Infections and infestations	24.1	Systematic Assessment	EG00014 affected176 at risk EG0017 affected180 at risk
Sinusitis	Infections and infestations	24.1	Systematic Assessment	EG00013 affected176 at risk EG0015 affected180 at risk
Upper respiratory tract infection	Infections and infestations	24.1	Systematic Assessment	EG00033 affected176 at risk EG00123 affected180 at risk
Urinary tract infection	Infections and infestations	24.1	Systematic Assessment	EG00012 affected176 at risk EG0017 affected180 at risk
Infusion related reaction	Injury, poisoning and procedural complications	24.1	Systematic Assessment	EG00024 affected176 at risk EG00124 affected180 at risk
Alanine aminotransferase increased	Investigations	24.1	Systematic Assessment	EG00018 affected176 at risk EG00115 affected180 at risk
Aspartate aminotransferase increased	Investigations	24.1	Systematic Assessment	EG00010 affected176 at risk EG0019 affected180 at risk
Blood bilirubin increased	Investigations	24.1	Systematic Assessment	EG00011 affected176 at risk EG0010 affected180 at risk
Lymphocyte count decreased	Investigations	24.1	Systematic Assessment	EG00012 affected176 at risk EG00113 affected180 at risk
Weight decreased	Investigations	24.1	Systematic Assessment	EG00014 affected176 at risk EG0012 affected180 at risk
White blood cell count decreased	Investigations	24.1	Systematic Assessment	EG00017 affected176 at risk EG00114 affected180 at risk
Decreased appetite	Metabolism and nutrition disorders	24.1	Systematic Assessment	EG00023 affected176 at risk EG00111 affected180 at risk
Hyperglycaemia	Metabolism and nutrition disorders	24.1	Systematic Assessment	EG00012 affected176 at risk EG00111 affected180 at risk
Hyperuricaemia	Metabolism and nutrition disorders	24.1	Systematic Assessment	EG00010 affected176 at risk EG0018 affected180 at risk
Hypokalaemia	Metabolism and nutrition disorders	24.1	Systematic Assessment	EG00015 affected176 at risk EG0015 affected180 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG00019 affected176 at risk EG00117 affected180 at risk
Back pain	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG00014 affected176 at risk EG00118 affected180 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG00023 affected176 at risk EG0019 affected180 at risk
Myalgia	Musculoskeletal and connective tissue disorders	24.1	Systematic Assessment	EG00010 affected176 at risk EG00112 affected180 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	24.1	Systematic Assessment	EG00018 affected176 at risk EG0011 affected180 at risk
Dizziness	Nervous system disorders	24.1	Systematic Assessment	EG00015 affected176 at risk EG0019 affected180 at risk
Headache	Nervous system disorders	24.1	Systematic Assessment	EG00026 affected176 at risk EG00117 affected180 at risk
Insomnia	Psychiatric disorders	24.1	Systematic Assessment	EG00014 affected176 at risk EG00111 affected180 at risk
Cough	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG00040 affected176 at risk EG00131 affected180 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG00018 affected176 at risk EG0017 affected180 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG00010 affected176 at risk EG0019 affected180 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	24.1	Systematic Assessment	EG00012 affected176 at risk EG0018 affected180 at risk
Dry skin	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG0009 affected176 at risk EG0016 affected180 at risk
Pruritus	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG00033 affected176 at risk EG0018 affected180 at risk
Rash	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG00020 affected176 at risk EG0019 affected180 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	24.1	Systematic Assessment	EG00014 affected176 at risk EG0014 affected180 at risk
Hypertension	Vascular disorders	24.1	Systematic Assessment	EG0006 affected176 at risk EG00111 affected180 at risk
Hypotension	Vascular disorders	24.1	Systematic Assessment	EG0009 affected176 at risk EG0011 affected180 at risk

ID	Term
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
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
D010797	Phthalimides
D010795	Phthalic Acids
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D010881	Piperidones
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D054833	Isoindoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring