Study of Lenalidomide to Evaluate Safety and Effectivenes... | NCT01197560

Label	Type	Description	Intervention Names
Lenalidomide	Experimental	Lenalidomide 25 mg capsules by mouth on days 1-21 of each 28 day cycle. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).	Drug: Lenalidomide
Investigators Choice	Active Comparator	One of the following: Gemcitabine, Oxaliplatin, Rituximab, or Etoposide	Drug: Gemcitabine Drug: Oxaliplatin Drug: Rituximab Drug: Etoposide

Name	Type	Description	Arm Group Labels	Other Names
Lenalidomide	Drug	Lenalidomide 25 mg orally for 21/28 days until Diffuse Large B-Cell Lymphoma (DLBCL) progressive disease. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).

Measure	Description	Time Frame
Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC)	An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease.	From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.
Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase	Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease.

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment	A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. 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

Measure	Description	Time Frame
Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase	Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response.	From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

Name	Affiliation	Role
Adrian Kilcoyne, MD	Celgene Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Providence St Joseph Medical Center/Cancer Center		Burbank	California	91505	United States
MD Anderson Cancer Center Orlando

PubMed Identifier	Type	Citation	Retractions
28381416	Result	Czuczman MS, Trneny M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A Phase 2/3 Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. doi: 10.1158/1078-0432.CCR-16-2818. Epub 2017 Apr 5.
21495023

ID	Title	Description
FG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.

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

Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC)

An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease.

The Modified Intent to Treat (mITT) population was defined as all participants randomized who had a diffuse large B-cell lymphoma (DLBCL) diagnosis and either germinal center B-cell subtype (GCB) or non-GCB subtype confirmed by central pathology, and who received at least one dose of study drug (lenalidomide or investigator's choice).

Posted

Number

95% Confidence Interval

percentage of participants

From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Units	Counts
Participants	OG00051 OG00151

Title

Denominators

Categories

ORR for All Participants

- ParticipantsOG00051
- ParticipantsOG00151

Title	Measurements
	OG00027.5(15.9 to 41.7)

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	Pertains to all participants; row 1	Fisher Exact		0.079														Superiority
OG001	Pertains to GCB Subtype; row 2	Fisher Exact

Primary

Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase

Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease.

mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.

Posted

Number

95% Confidence Interval

Percentage of participants

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.

Other Pre-specified

Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase

Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response.

Posted

Median

95% Confidence Interval

percentage of participants

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Other Pre-specified

Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase

A complete response was defined as participants with a complete response (CR), or unconfirmed complete response (CRu) based on IWG 1999 Response Criteria for NHL as assessed by the investigator. A CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRu) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

Posted

Number

95% Confidence Interval

percentage of participants

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.

Other Pre-specified

Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase

Duration of overall response was calculated as the time of initial response (CR+CRu+PR) until documented disease progression determinted by computerized scan CT scan or MRI or death due to lymphoma, whichever occurred earlier, for participants who responded.

For DoR, the population included participants who had an overall response.

Posted

Median

95% Confidence Interval

Weeks

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Other Pre-specified

Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase

Duration of complete response was defined as the time from the first documented complete response (CR + CRu) until the first disease progression or death for participants who had a CR.

For DoCR, the population included participants who had a CR.

Posted

Median

95% Confidence Interval

Weeks

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Other Pre-specified

Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase

Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause.

Posted

Median

95% Confidence Interval

Weeks

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Other Pre-specified

Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase

Overall survival was defined as time from randomization until death of any cause.

Posted

Median

95% Confidence Interval

Weeks

From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Secondary

Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment

A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.

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

Safety Population included all participants who received at least one dose of lenalidomide or IC regimen.

Posted

Count of Participants

Participants

From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.

Secondary

Stage 2: Overall Response Rate (ORR)

ORR is defined as: Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).

ORR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Secondary

Stage 2: Duration of Response (DoR)

Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).

DoR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Secondary

Stage 2: Overall Survival (OS)

Overall survival was defined as time from randomization until death of any cause.

OS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Other Pre-specified

Stage 2: Progression-Free Survival

Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG].

PFS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Secondary

Stage 2: Duration of Complete Response

Length of time of complete response (Complete Response + Complete Response unconfirmed) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).

Duration of CR was not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Secondary

Stage 2: Overall Response Rate for With a Duration of Response Lasting ≥ 16 Weeks

Complete Response + Complete Response unconfirmed + Partial Response for participants with a duration of response lasting ≥ 16 weeks based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).

Overall Response Rate for with a Duration of Response Lasting ≥ 16 weeks was not analyzed: the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Secondary

Stage 2: Time to Progression

Length of time until disease progression occurs

Time to progression was not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (Control Arm)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.

Secondary

Stage 2: Health Related Quality of Life Questionnaires

Quality of Life based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D assessments

Health Related Quality of Life Instruments were not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.

Posted

Approximately 3.5 years

ID	Title	Description
OG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
OG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0013 affected55 at risk
FEBRILE BONE MARROW APLASIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk
LYMPH NODE PAIN	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
CARDIAC ARREST	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
CARDIAC FAILURE CONGESTIVE	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
CARDIO-RESPIRATORY ARREST	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
SUPRAVENTRICULAR TACHYCARDIA	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
COLITIS ULCERATIVE	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
DUODENAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
ILEUS	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
LARGE INTESTINE PERFORATION	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
LOWER GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
SMALL INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
VOMITING	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
ASTHENIA	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0012 affected55 at risk
DEATH	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
FATIGUE	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
GENERAL PHYSICAL HEALTH DETERIORATION	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0012 affected55 at risk
MULTIPLE ORGAN DYSFUNCTION SYNDROME	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
PERFORMANCE STATUS DECREASED	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
PYREXIA	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0012 affected55 at risk
BILE DUCT OBSTRUCTION	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
CELLULITIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0014 affected55 at risk
DIARRHOEA INFECTIOUS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
LUNG ABSCESS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
LUNG INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
LYMPH NODE ABSCESS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
NEUTROPENIC SEPSIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
PNEUMONIA	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
SEPSIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0012 affected55 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0012 affected55 at risk
STAPHYLOCOCCAL SEPSIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
SUBCUTANEOUS ABSCESS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0010 affected55 at risk
WOUND INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
FALL	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
BLOOD CREATININE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
NEUTROPHIL COUNT DECREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
HYPERCALCAEMIA	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
TUMOUR LYSIS SYNDROME	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
JOINT SWELLING	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0012 affected55 at risk
BASAL CELL CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
DIFFUSE LARGE B-CELL LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG00110 affected55 at risk
GASTROINTESTINAL TRACT ADENOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
NON-HODGKIN'S LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
RECTOSIGMOID CANCER METASTATIC	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
TUMOUR FLARE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
CAUDA EQUINA SYNDROME	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
CEREBROVASCULAR ACCIDENT	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
DIZZINESS	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
NERVE ROOT COMPRESSION	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
SEIZURE	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
ANXIETY	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
MENTAL STATUS CHANGES	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0012 affected55 at risk
HYDRONEPHROSIS	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
NEPHROTIC SYNDROME	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
ACUTE PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0011 affected55 at risk
LARYNGEAL OBSTRUCTION	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
PHARYNGEAL INFLAMMATION	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0011 affected55 at risk
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0011 affected55 at risk
STRIDOR	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0010 affected55 at risk
FUNGATING WOUND	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
EMBOLISM	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk
HYPOTENSION	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0011 affected55 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00017 affected54 at risk EG00131 affected55 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0018 affected55 at risk
LYMPHOPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0015 affected55 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00023 affected54 at risk EG00118 affected55 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected54 at risk EG00117 affected55 at risk
TACHYCARDIA	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
HYPOACUSIS	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
VERTIGO	Ear and labyrinth disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0011 affected55 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected54 at risk EG00112 affected55 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00016 affected54 at risk EG00116 affected55 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected54 at risk EG00116 affected55 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected54 at risk EG0013 affected55 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected54 at risk EG00123 affected55 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0015 affected55 at risk
VOMITING	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected54 at risk EG00111 affected55 at risk
ASTHENIA	General disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected54 at risk EG00113 affected55 at risk
CHILLS	General disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk
FATIGUE	General disorders	MedDRA 21.0	Systematic Assessment	EG00019 affected54 at risk EG00116 affected55 at risk
NON-CARDIAC CHEST PAIN	General disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0011 affected55 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected54 at risk EG00110 affected55 at risk
PYREXIA	General disorders	MedDRA 21.0	Systematic Assessment	EG00016 affected54 at risk EG00118 affected55 at risk
BRONCHITIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0006 affected54 at risk EG0010 affected55 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0016 affected55 at risk
LUNG INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
PNEUMONIA	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
RHINITIS	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0014 affected55 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0005 affected54 at risk EG0015 affected55 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0014 affected55 at risk
DRUG PRESCRIBING ERROR	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0005 affected54 at risk EG0011 affected55 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0014 affected55 at risk
BLOOD CREATININE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0014 affected55 at risk
BLOOD LACTATE DEHYDROGENASE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
NEUTROPHIL COUNT DECREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0017 affected55 at risk
PLATELET COUNT DECREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0019 affected55 at risk
WHITE BLOOD CELL COUNT DECREASED	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0015 affected55 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected54 at risk EG00115 affected55 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0016 affected55 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected54 at risk EG00110 affected55 at risk
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0007 affected54 at risk EG0015 affected55 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0018 affected55 at risk
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0012 affected55 at risk
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0010 affected55 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0014 affected55 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected54 at risk EG0015 affected55 at risk
DIFFUSE LARGE B-CELL LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
TUMOUR FLARE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0005 affected54 at risk EG0010 affected55 at risk
DIZZINESS	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0015 affected55 at risk
DYSGEUSIA	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0013 affected55 at risk
HEADACHE	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0016 affected55 at risk
HYPOAESTHESIA	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
LETHARGY	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0011 affected55 at risk
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0015 affected55 at risk
ANXIETY	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected54 at risk EG0015 affected55 at risk
DEPRESSION	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk
INSOMNIA	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0012 affected55 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected54 at risk EG00110 affected55 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected54 at risk EG00112 affected55 at risk
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected54 at risk EG0013 affected55 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected54 at risk EG0014 affected55 at risk
DRY SKIN	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0010 affected55 at risk
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk
PRURITUS GENERALISED	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected54 at risk EG0013 affected55 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected54 at risk EG0012 affected55 at risk
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0011 affected55 at risk
HYPOTENSION	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected54 at risk EG0013 affected55 at risk

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D008228	Lymphoma, Non-Hodgkin
D012008	Recurrence

ID	Term
D016393	Lymphoma, B-Cell
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
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
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
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D056831	Coordination Complexes
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
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates

ID	Title	Description
BG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
BG001	Investigators Choice (IC)	Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lenalidomide	Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.	48	54	31	54	53	54
EG001	Investigator's Choice	Investigator's Choice	51	55	42	55	52	55

ID	Term
D000077269	Lenalidomide
D000093542	Gemcitabine
D000077150	Oxaliplatin
D000069283	Rituximab
D005047	Etoposide