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Trial record 1 of 4 for:    lenalidomide R-CHOP | Lymphoma | Italy
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Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-cell Lymphoma (ROBUST)

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ClinicalTrials.gov Identifier: NCT02285062
Recruitment Status : Active, not recruiting
First Posted : November 6, 2014
Results First Posted : March 30, 2020
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Lymphoma, Large B-Cell, Diffuse
Interventions Drug: lenalidomide
Drug: Placebo
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: prednisone
Drug: vincristine
Enrollment 570
Recruitment Details The study has completed enrollment but is ongoing. 177 community, academic and government sites randomized participants in Australia, Belgium, Canada, China, the Czech Republic, France, Ireland, Israel, Italy, Japan, the Netherlands, New Zealand, Poland, Portugal, Russia, South Korea, Spain, Switzerland, Taiwan, Turkey and the United States.
Pre-assignment Details

Participants were randomized in a 1:1 ratio to either lenalidomide-(R2)CHOP or placebo-R-CHOP, and stratified by International Prognostic Index (IPI) Score 2 or ≥ 3, age: < 65 or ≥ 65 years and presence of bulky disease: diameter of the lesion ≥ 7.0 cm (bulky) or < 7.0 cm (nonbulky).

.

Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice. Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Period Title: Overall Study
Started 285 285
Received Study Treatment 283 284
Ongoing Study Treatment 0 0
Completed [1] 207 201
Not Completed 78 84
Reason Not Completed
Withdrawal by Subject             12             17
Death             58             62
Lost to Follow-up             8             5
[1]
Completed = Ongoing in the Follow-Up Period
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP Total
Hide Arm/Group Description Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice. Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice. Total of all reporting groups
Overall Number of Baseline Participants 285 285 570
Hide Baseline Analysis Population Description
The Intent-to-treat (ITT) population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 285 participants 285 participants 570 participants
62.5  (11.72) 63.9  (9.35) 63.2  (10.62)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
< 65
138
  48.4%
137
  48.1%
275
  48.2%
≥ 65
147
  51.6%
148
  51.9%
295
  51.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
Female
121
  42.5%
142
  49.8%
263
  46.1%
Male
164
  57.5%
143
  50.2%
307
  53.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
Hispanic or Latino
14
   4.9%
17
   6.0%
31
   5.4%
Not Hispanic or Latino
270
  94.7%
267
  93.7%
537
  94.2%
Unknown or Not Reported
1
   0.4%
1
   0.4%
2
   0.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
White
173
  60.7%
183
  64.2%
356
  62.5%
Asian
101
  35.4%
89
  31.2%
190
  33.3%
Black or African American
2
   0.7%
3
   1.1%
5
   0.9%
Other
3
   1.1%
2
   0.7%
5
   0.9%
Not Collected or Reported
6
   2.1%
8
   2.8%
14
   2.5%
Body Surface Area (BSA)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 285 participants 285 participants 570 participants
1.780  (0.2167) 1.775  (0.2101) 1.777  (0.2132)
[1]
Measure Description: Body surface area is the calculated surface of a human body. BSA is often considered a more accurate measure of metabolic mass than body weight, since it's less affected by irregular amounts of fat tissue.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
0 = Fully Active
129
  45.3%
111
  38.9%
240
  42.1%
1 = Restrictive but ambulatory
104
  36.5%
118
  41.4%
222
  38.9%
2 = Ambulatory but unable to work
52
  18.2%
56
  19.6%
108
  18.9%
[1]
Measure Description: The ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: 0 = Fully active, no restrictions; 1 = Restricted activity but ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities; 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled, no self-care, confined to bed or chair; 5 = Dead
Creatinine Clearance   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 285 participants 284 participants 569 participants
92.08  (35.576) 90.19  (31.040) 91.14  (33.373)
[1]
Measure Description: Creatinine is a waste product from the normal breakdown of muscle tissue. As creatinine is produced, it's filtered through the kidneys and excreted in urine. Doctors measure the blood creatinine level as a test of kidney function.
[2]
Measure Analysis Population Description: One creatinine clearance value is missing.
International Prognostic Index (IPI) Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
= 2
121
  42.5%
120
  42.1%
241
  42.3%
≥ 3
164
  57.5%
165
  57.9%
329
  57.7%
[1]
Measure Description:

The IPI score is a clinical tool developed to aid in predicting the prognosis of patients with aggressive non-Hodgkin's lymphoma, including DLBCL. One point is assigned for each of the following risk factors:

Age greater than 60 years, Stage III or IV disease, elevated serum lactate dehydrogenase (LDH), ECOG performance status of 2, 3, or 4, more than 1 extranodal site.

The sum of the points allotted correlates with the following risk groups:

Low risk (0-1 points) Low-intermediate risk (2 points) High-intermediate risk (3 points) High risk (4-5 points)

Presence of Bulky Disease  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
< 7.0 cm (Non-Bulky Disease)
188
  66.0%
186
  65.3%
374
  65.6%
≥ 7.0 cm (Bulky Disease)
97
  34.0%
99
  34.7%
196
  34.4%
Disease Stage of Diffuse Large B-Cell Lymphoma at Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 285 participants 285 participants 570 participants
Stage I
0
   0.0%
1
   0.4%
1
   0.2%
Stage II
37
  13.0%
32
  11.2%
69
  12.1%
Stage III
80
  28.1%
98
  34.4%
178
  31.2%
Stage IV
168
  58.9%
154
  54.0%
322
  56.5%
[1]
Measure Description: The criteria for clinical stage (Ann Arbor staging) are as below: I: involvement of a single nodal region. II: involvement of 2 or more lymph node regions on the same side of the diaphragm. III: involvement of lymph node regions on both sides of the diaphragm. IV: disseminated involvement of 1 or more extra-lymphatic sites with or without associated lymph node involvement.
1.Primary Outcome
Title Kaplan-Meier Estimate of Progression Free Survival (PFS)
Hide Description Progression free survival was defined as the time (months) from the date of randomization to the date of disease progression or death (any cause), whichever occurred earlier and was assessed by the Independent Response Adjudication Committee (IRAC). Relapse from complete response (CR) was considered as disease progression throughout the study. Disease progression was determined based on the Revised Response Criteria for Malignant Lymphoma. The PFS analysis was based on the censoring rules using the Food and Drug Administration (FDA) Guidance. Participants who did not experience disease progression and who did not die before the clinical data cutoff date were censored at the date of last adequate response assessment.
Time Frame From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(35.5 to NA)
[1]
Median PFS and the upper and lower 95% confidence interval was not reached due to the low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2864
Comments [Not Specified]
Method Log Rank
Comments Stratified by: IPI score (2 or ≥ 3), presence or absence of bulky disease (diameter of the lesion ≥ 7 cm or < 7 cm), and age (< 65 or ≥ 65 years).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.849
Confidence Interval (2-Sided) 95%
0.632 to 1.140
Estimation Comments Hazard ratio was derived from Cox proportional hazard model adjusting for the 3 stratification factors
2.Secondary Outcome
Title Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS)
Hide Description

EFS was defined as the time (months) from randomization until occurrence of one of the following events, whichever occurred first:

  • Disease progression
  • Initiation of subsequent systemic anti-lymphoma therapy
  • Death due to any cause The assessment of EFS was conducted by the IRAC using the International Working Group (IWG) criteria for NHL. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as an EFS event (initiation of subsequent systemic anti-lymphoma therapy) if the decision to treat and the location to be treated was determined prior to randomization. Participants who did not experience any of the events defined in the categories above before the clinical data cutoff date were censored at date last known alive.
Time Frame From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(31.3 to NA)
[1]
Median EFS was not reached due to the low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7294
Comments [Not Specified]
Method Log Rank
Comments Stratified by: IPI score (2 or ≥ 3), presence or absence of bulky disease (diameter of the lesion ≥ 7 cm or < 7 cm), and age (< 65 or ≥ 65 years).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.038
Confidence Interval (2-Sided) 95%
0.802 to 1.344
Estimation Comments Hazard ratio was derived from Cox proportional hazard model adjusting for the 3 stratification factors.
3.Secondary Outcome
Title K-M Estimate of Overall Survival (OS)
Hide Description Overall survival was assessed by the IRAC and defined as time from randomization until death of any cause. Participants who withdrew consent were censored at the time of withdrawal. Participants who were still alive before the clinical data cutoff date and participants who were lost to follow-up were censored at date last known alive.
Time Frame From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
K-M estimate median OS was not reached due to low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6433
Comments [Not Specified]
Method Log Rank
Comments Log-rank test stratified by 3 factors: IPI score (2 or ≥ 3), presence of bulky disease (bulky or nonbulky), and age (< 65 or ≥ 65).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.925
Confidence Interval (2-Sided) 95%
0.646 to 1.323
Estimation Comments Hazard ratio was derived from Cox proportional hazard model adjusting for the 3 stratification factors.
4.Secondary Outcome
Title Percentage of Participants Who Achieved a Complete Response (CR)
Hide Description The percentage of participants who achieved a CR after initiation of the study treatment and prior to initiation of subsequent systemic antilymphoma therapy as assessed by the IRAC. A CR = complete metabolic response; target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow per International Working Group (IWG) 2014 for Non-Hodgkin's Lymphoma (NHL). Participants who did not have any adequate response assessments during this period were not considered as responders.
Time Frame From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not. Participants who had a CR.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
69.1
(63.4 to 74.4)
64.9
(59.1 to 70.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2933
Comments Obtained from CMH test adjusting for stratification factors: IPI score (2 or ≥ 3), presence of bulky disease (bulky or nonbulky), and age (< 65 or ≥ 65)
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Who Achieved an Objective Response
Hide Description An objective response = percentage of participants who achieved a complete response or partial response after initiation of the treatment and prior to initiation of subsequent systemic anti-lymphoma therapy. A CR = complete metabolic response; Target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow. 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 nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter; no new lesions. Participants who did not have any adequate response assessments during this period were not considered as responders.
Time Frame From randomization date up to the data cut off date of 15 March 2019; median total treatment duration was 18.10 weeks for both treatment arms; range = 1.6 to 29.0 weeks for R2-CHOP arm and 0.3 to 22.9 weeks for placebo-R-CHOP arm
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not. Participants who had a PR or better.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
90.9
(86.9 to 94.0)
90.9
(86.9 to 94.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9964
Comments Obtained from CMH test adjusting for stratification factors: IPI score (2 or ≥ 3), presence of bulky disease (bulky or nonbulky), and age (< 65 or ≥ 65)
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
6.Secondary Outcome
Title K-M Estimate of Duration of Complete Response
Hide Description Duration of complete response was calculated for complete responders only and was defined as the time from documented initial complete response prior to initiation of subsequent systemic antilymphoma therapy until documented disease progression or death, whichever occurred earlier. Participants who had not progressed or died at the time of the analysis were censored at the date of last response assessment demonstrating no disease progression. Participants who changed treatment without evidence of disease progression were censored at the last assessment showing no progression prior to treatment change.
Time Frame From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not. Participants who had a response.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 197 185
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Median duration of CR could not be estimated due to the low number of events.
[2]
Median duration of CR could not be estimated due to due to the low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2143
Comments [Not Specified]
Method Log Rank
Comments Stratified by: IPI score (2 or ≥ 3), presence or absence of bulky disease (diameter of the lesion ≥ 7 cm or < 7 cm), and age (< 65 or ≥ 65 years).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.776
Confidence Interval (2-Sided) 95%
0.521 to 1.157
Estimation Comments HR was derived from COX model adjusting for the 3 stratification factors mentioned above.
7.Secondary Outcome
Title K-M Estimate of Time to Next Lymphoma Therapy (TTNLT)
Hide Description Time to next lymphoma therapy was defined as the time from randomization to the time of treatment change for the next lymphoma treatment. Participants without treatment change were censored at date last known alive. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as treatment change for the next lymphoma therapy if the decision to treat and the location to be treated were determined prior to randomization.
Time Frame From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median time to next lymphoma treatment was not reached due to low number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3150
Comments [Not Specified]
Method Log Rank
Comments Stratified by: IPI score (2 or ≥ 3), presence or absence of bulky disease (diameter of the lesion ≥ 7 cm or < 7 cm), and age (< 65 or ≥ 65 years).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.167
Confidence Interval 95%
0.856 to 1.590
Estimation Comments HR is derived from Cox model
8.Secondary Outcome
Title Number of Participants With a Treatment Emergent Adverse Event (TEAE)
Hide Description

A TEAE was defined as an AE that begins or worsens in intensity or 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 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death
Time Frame From the first dose of study treatment up to 28 days after the last dose of LEN/placebo or any component of R-CHOP including the optional 2 additional doses of rituximab if administered; up to 15 March 2019; maximum treatment duration = 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who had received at least one dose of investigational product.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 283 284
Measure Type: Count of Participants
Unit of Measure: Participants
≥ 1 TEAE
281
  99.3%
279
  98.2%
≥1 TEAE Related to Lenalidomide (LEN)/Placebo
249
  88.0%
222
  78.2%
≥ 1 TEAE Related to RCHOP
271
  95.8%
254
  89.4%
≥ 1 Grade (GR) 3 TEAE
203
  71.7%
172
  60.6%
≥ 1 GR 4 TEAE
154
  54.4%
129
  45.4%
≥ 1 GR 3 or 4 TEAE
221
  78.1%
203
  71.5%
≥1 GR 3 or 4 TEAE Related to LEN/Placebo (PBO)
185
  65.4%
157
  55.3%
≥ 1 GR 3 or 4 TEAE related to R- CHOP
200
  70.7%
177
  62.3%
≥ 1 GR 5 TEAE (Leading to Death)
6
   2.1%
8
   2.8%
≥ 1 GR 5 TEAE (Death) Related to LEN/PBO
3
   1.1%
4
   1.4%
≥ 1 GR 5 TEAE (Death) related to R-CHOP
3
   1.1%
3
   1.1%
≥ 1 Treatment-Emergent SAE
104
  36.7%
88
  31.0%
≥ 1 Treatment-Emergent SAE Related to LEN/PBO
69
  24.4%
57
  20.1%
≥1 Treatment-Emergent SAE Related to R-CHOP
67
  23.7%
60
  21.1%
≥1 TEAE Leading to Discontinuing (DC) LEN/PBO
49
  17.3%
32
  11.3%
≥1 TEAE Leading to DC R-CHOP
9
   3.2%
9
   3.2%
≥1 TEAE Leading to DC of LEN/placebo and R-CHOP
7
   2.5%
9
   3.2%
≥1 TEAE Lead to Reduction/ Interruption LEN/PBO
159
  56.2%
129
  45.4%
≥1 TEAE Leading to Dose Reduction of LEN/PBO
68
  24.0%
41
  14.4%
≥1 TEAE Leading to Dose Interruption of LEN/PBO
144
  50.9%
122
  43.0%
≥1 TEAE Lead to Dose Reduction/Interruption R-CHOP
97
  34.3%
82
  28.9%
≥ 1 TEAE Leading to Dose Reduction of R-CHOP
54
  19.1%
45
  15.8%
≥ 1 TEAE Leading to Dose Interruption of R-CHOP
64
  22.6%
53
  18.7%
9.Secondary Outcome
Title Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire
Hide Description The completion rate for FACT-Lym assessments was judged by looking at the number of completed FACT-Lym assessments at each time point. The FACT-Lym was considered completed if at least 1 calculable score was present. Completion rates were calculated as the number and percentage of participants out of the total number of patients in the ITT population and summarized by visit/cycle and treatment group. The FACT-Lym is a health related quality of life (HRQoL) questionnaire targeted to the management of chronic illness, predominantly within oncology and is considered an extension of the FACT-General questionnaire.
Time Frame Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Measure Type: Number
Unit of Measure: Percentage of Participants
Screening 98.6 98.2
Midcycle = After Cycle 3, but before Cycle 4 87.0 86.3
End of Treatment (EoT) = 3-4 weeks after C6 76.1 79.6
Follow-Up Period: Week 34 67.7 69.5
10.Secondary Outcome
Title Percentage of Participants Who Completed the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Health Related Quality of Life (HR-QoL) Questionnaire
Hide Description The completion rate for EQ-5D assessments was judged by looking at the number of completed assessments at each time point. Completion rates were calculated as the number and percentage of participants out of the total number of patients in the ITT population and summarized by visit/cycle and treatment group. The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems". The instrument is scored using the United Kingdom (UK) index ranges from -0.594 - 1, where 0 equates to death and 1 equates to full health -0.594 is considered 'worse than death'.
Time Frame Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized into the trial, regardless of whether they received study treatment or not.
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 285 285
Measure Type: Number
Unit of Measure: Percentage of Participants
Screening 98.9 97.9
Midcycle 87.0 86.3
End of Treatment (EoT) 76.5 79.6
Follow-Up Period: Week 34 68.1 69.1
11.Secondary Outcome
Title Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale
Hide Description The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The physical well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL.
Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable FACT-Lym score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 257 257
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 246 participants 244 participants
-0.7  (5.91) 0.2  (5.40)
C6 D1 Number Analyzed 140 participants 137 participants
-0.0  (6.35) 0.9  (6.02)
EoT = 3-4 weeks after C6 Number Analyzed 214 participants 226 participants
1.5  (5.53) 0.7  (5.72)
Follow-Up Period: Week 34 Number Analyzed 191 participants 196 participants
2.8  (5.24) 2.6  (5.55)
12.Secondary Outcome
Title Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale
Hide Description

The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms such as pain, itching, night sweats,trouble sleeping, fatigue and trouble concentrating and concerns regarding lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment.

All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The Additional Concerns subscale ranges from 0 to 60, where higher scores reflect better HRQoL.

Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable FACT-Lym score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 257 255
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 244 participants 242 participants
3.8  (10.33) 4.1  (8.88)
C6 D1 Number Analyzed 139 participants 135 participants
5.8  (11.11) 5.2  (9.40)
EoT = 3-4 weeks after C6 Number Analyzed 212 participants 222 participants
6.6  (10.11) 4.5  (9.62)
Follow-Up Period: Week 34 Number Analyzed 189 participants 195 participants
8.3  (10.61) 6.5  (9.20)
13.Secondary Outcome
Title Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale
Hide Description The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The functional well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL.
Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable FACT-Lym score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 258 256
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 246 participants 242 participants
-0.5  (6.12) 0.5  (5.84)
C6 D1 Number Analyzed 139 participants 135 participants
0.0  (6.24) 1.4  (5.63)
EoT = 3-4 weeks after C6 Number Analyzed 214 participants 224 participants
1.0  (6.53) 0.7  (6.71)
Follow-Up Period: Week 34 Number Analyzed 191 participants 196 participants
2.3  (6.65) 3.1  (6.17)
14.Secondary Outcome
Title Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI)
Hide Description The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The FACT-Lym TOI is calculated by summing the Physical Well-being, Functional Well-being and Additional Concerns scores and has a range of 0 to 116. Higher scores reflect better HRQoL or fewer symptoms.
Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
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Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable FACT-Lym score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 256 254
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 244 participants 240 participants
2.6  (18.26) 4.6  (16.49)
C6 D1 Number Analyzed 138 participants 133 participants
5.9  (19.85) 7.5  (17.40)
EoT = 3-4 weeks after C6 Number Analyzed 212 participants 220 participants
9.1  (18.51) 5.8  (18.64)
Follow-Up Period: Week 34 Number Analyzed 189 participants 193 participants
13.5  (18.74) 12.2  (17.97)
15.Secondary Outcome
Title Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score
Hide Description The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems". The instrument is scored as a single summary index using one of the available EQ-5D-3L value sets; in this study the UK scoring weights 9 were used. The UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health (-0.594 is considered 'worse than death').
Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
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Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable EQ-5D score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 257 255
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 245 participants 241 participants
0.08  (0.308) 0.08  (0.281)
C6 D1 Number Analyzed 139 participants 135 participants
0.10  (0.325) 0.14  (0.330)
EoT = 3-4 weeks after C6 Number Analyzed 214 participants 223 participants
0.10  (0.309) 0.06  (0.319)
Follow-Up Period: Week 34 Number Analyzed 190 participants 195 participants
0.15  (0.293) 0.09  (0.311)
16.Secondary Outcome
Title Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS)
Hide Description The EQ-5D-3L questionnaire includes a visual analogue scale which records the respondent's self-rated health on a vertical, 0-100 scale where 100 = "Best imaginable health state" and 0 = "Worst imaginable health state". Higher scores again indicate better HRQoL and positive change scores indicate that post screening values were higher than those observed at screening. The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems".
Time Frame Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as all participants in the ITT population who had: at least one baseline and the corresponding post-baseline calculable EQ-5D score assessment; where post-baseline is any subsequent time excluding unscheduled visits (i.e. at Midcycle, C6D1, EOT or a follow-up visit).
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description:
Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
Overall Number of Participants Analyzed 256 255
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Midcycle Number Analyzed 245 participants 242 participants
4.0  (20.5) 3.0  (18.2)
C6 D1 Number Analyzed 138 participants 135 participants
6.0  (23.5) 9.0  (24.5)
EoT = 3-4 weeks after C6 Number Analyzed 213 participants 224 participants
8.0  (18.7) 6.0  (21.5)
Follow-Up Period: Week 34 Number Analyzed 190 participants 195 participants
12.0  (20.2) 9  (21.4)
Time Frame AEs were monitored from the first dose of study treatment up to 28 days after the last dose of LEN/PBO or any component of R-CHOP including the optional 2 additional doses of rituximab; median total treatment duration was 18.10 weeks for both arms; up to 15 March 2019
Adverse Event Reporting Description All-Cause Mortality is reported for the entire duration of the study including follow-up. (ITT Population)
 
Arm/Group Title Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Hide Arm/Group Description Participants received lenalidomide 15 mg capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 cycles. Treatment continued until completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, whichever occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice. Participants received identically matching placebo capsules on days 1 to 14 of each 21 day treatment cycle followed by R-CHOP: rituximab 375 mg/m^2 by intravenous (IV) administration on Day 1, doxorubicin 50 mg/m^2 IV on Day 1, vincristine 1.4 mg/m^2 IV on Day 1 (maximum dose of 2.0 mg total), cyclophosphamide 750 mg/m^2 IV on Day 1 and oral or IV prednisone/prednisolone 100 mg on Day 1 to Day 5 of each 21 day treatment cycle for 6 to 8 cycles. Treatment continued until 6-8 cycles were completed, unless unacceptable toxicity, treatment change, disease progression, or withdrawal of consent, occurred first. An additional two doses (1 dose per 21-day cycle) of single agent rituximab after the 6 cycles of treatment were completed if considered standard of care per local practice.
All-Cause Mortality
Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   58/285 (20.35%)   62/285 (21.75%) 
Hide Serious Adverse Events
Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   104/283 (36.75%)   88/284 (30.99%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  1/283 (0.35%)  1/284 (0.35%) 
Anaemia  1  6/283 (2.12%)  6/284 (2.11%) 
Cytopenia  1  1/283 (0.35%)  0/284 (0.00%) 
Febrile neutropenia  1  31/283 (10.95%)  14/284 (4.93%) 
Leukopenia  1  2/283 (0.71%)  0/284 (0.00%) 
Lymphadenopathy  1  0/283 (0.00%)  1/284 (0.35%) 
Neutropenia  1  19/283 (6.71%)  13/284 (4.58%) 
Splenic necrosis  1  0/283 (0.00%)  1/284 (0.35%) 
Thrombocytopenia  1  16/283 (5.65%)  1/284 (0.35%) 
Cardiac disorders     
Acute coronary syndrome  1  1/283 (0.35%)  0/284 (0.00%) 
Acute myocardial infarction  1  2/283 (0.71%)  0/284 (0.00%) 
Arrhythmia supraventricular  1  1/283 (0.35%)  0/284 (0.00%) 
Atrial fibrillation  1  2/283 (0.71%)  4/284 (1.41%) 
Atrial flutter  1  0/283 (0.00%)  1/284 (0.35%) 
Cardiac arrest  1  0/283 (0.00%)  1/284 (0.35%) 
Cardiac disorder  1  0/283 (0.00%)  1/284 (0.35%) 
Cardiac failure  1  0/283 (0.00%)  3/284 (1.06%) 
Cardiac failure congestive  1  0/283 (0.00%)  1/284 (0.35%) 
Coronary artery disease  1  0/283 (0.00%)  1/284 (0.35%) 
Sinus tachycardia  1  0/283 (0.00%)  1/284 (0.35%) 
Gastrointestinal disorders     
Abdominal distension  1  1/283 (0.35%)  0/284 (0.00%) 
Abdominal pain  1  4/283 (1.41%)  0/284 (0.00%) 
Dental caries  1  0/283 (0.00%)  1/284 (0.35%) 
Diarrhoea  1  6/283 (2.12%)  4/284 (1.41%) 
Diverticular perforation  1  0/283 (0.00%)  1/284 (0.35%) 
Enterocutaneous fistula  1  0/283 (0.00%)  1/284 (0.35%) 
Flatulence  1  1/283 (0.35%)  0/284 (0.00%) 
Gastric haemorrhage  1  2/283 (0.71%)  1/284 (0.35%) 
Gastroduodenal haemorrhage  1  0/283 (0.00%)  1/284 (0.35%) 
Gastrointestinal haemorrhage  1  1/283 (0.35%)  0/284 (0.00%) 
Haematochezia  1  1/283 (0.35%)  0/284 (0.00%) 
Intestinal obstruction  1  1/283 (0.35%)  0/284 (0.00%) 
Large intestine perforation  1  0/283 (0.00%)  1/284 (0.35%) 
Nausea  1  2/283 (0.71%)  2/284 (0.70%) 
Neutropenic colitis  1  0/283 (0.00%)  1/284 (0.35%) 
Stomatitis  1  2/283 (0.71%)  0/284 (0.00%) 
Vomiting  1  3/283 (1.06%)  1/284 (0.35%) 
General disorders     
Asthenia  1  2/283 (0.71%)  1/284 (0.35%) 
Death  1  1/283 (0.35%)  0/284 (0.00%) 
Extravasation  1  1/283 (0.35%)  0/284 (0.00%) 
Face oedema  1  1/283 (0.35%)  0/284 (0.00%) 
General physical health deterioration  1  1/283 (0.35%)  0/284 (0.00%) 
Hypothermia  1  1/283 (0.35%)  0/284 (0.00%) 
Malaise  1  1/283 (0.35%)  0/284 (0.00%) 
Non-cardiac chest pain  1  0/283 (0.00%)  1/284 (0.35%) 
Oedema peripheral  1  1/283 (0.35%)  0/284 (0.00%) 
Pyrexia  1  7/283 (2.47%)  9/284 (3.17%) 
Sudden cardiac death  1  1/283 (0.35%)  0/284 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/283 (0.35%)  0/284 (0.00%) 
Drug-induced liver injury  1  1/283 (0.35%)  0/284 (0.00%) 
Hepatic function abnormal  1  0/283 (0.00%)  1/284 (0.35%) 
Hepatitis  1  0/283 (0.00%)  1/284 (0.35%) 
Jaundice cholestatic  1  1/283 (0.35%)  0/284 (0.00%) 
Liver injury  1  0/283 (0.00%)  1/284 (0.35%) 
Immune system disorders     
Contrast media allergy  1  0/283 (0.00%)  1/284 (0.35%) 
Infections and infestations     
Abdominal infection  1  0/283 (0.00%)  1/284 (0.35%) 
Anal abscess  1  1/283 (0.35%)  0/284 (0.00%) 
Appendicitis  1  1/283 (0.35%)  1/284 (0.35%) 
Arthritis bacterial  1  1/283 (0.35%)  0/284 (0.00%) 
Bacterial infection  1  1/283 (0.35%)  0/284 (0.00%) 
Bronchitis  1  0/283 (0.00%)  1/284 (0.35%) 
Campylobacter gastroenteritis  1  1/283 (0.35%)  0/284 (0.00%) 
Cellulitis  1  3/283 (1.06%)  0/284 (0.00%) 
Clostridium difficile colitis  1  1/283 (0.35%)  1/284 (0.35%) 
Cytomegalovirus infection  1  1/283 (0.35%)  1/284 (0.35%) 
Device related infection  1  1/283 (0.35%)  2/284 (0.70%) 
Device related sepsis  1  2/283 (0.71%)  0/284 (0.00%) 
Escherichia sepsis  1  1/283 (0.35%)  0/284 (0.00%) 
Escherichia urinary tract infection  1  1/283 (0.35%)  0/284 (0.00%) 
Groin abscess  1  1/283 (0.35%)  0/284 (0.00%) 
Hepatitis B  1  0/283 (0.00%)  1/284 (0.35%) 
Herpes zoster  1  0/283 (0.00%)  1/284 (0.35%) 
Influenza  1  1/283 (0.35%)  0/284 (0.00%) 
Klebsiella infection  1  1/283 (0.35%)  0/284 (0.00%) 
Lower respiratory tract infection  1  0/283 (0.00%)  1/284 (0.35%) 
Lower respiratory tract infection bacterial  1  1/283 (0.35%)  0/284 (0.00%) 
Lung infection  1  4/283 (1.41%)  2/284 (0.70%) 
Neutropenic sepsis  1  1/283 (0.35%)  0/284 (0.00%) 
Osteomyelitis  1  0/283 (0.00%)  1/284 (0.35%) 
Parainfluenzae virus infection  1  1/283 (0.35%)  0/284 (0.00%) 
Pharyngitis  1  0/283 (0.00%)  1/284 (0.35%) 
Pneumocystis jirovecii pneumonia  1  0/283 (0.00%)  1/284 (0.35%) 
Pneumonia  1  11/283 (3.89%)  7/284 (2.46%) 
Pulmonary sepsis  1  1/283 (0.35%)  0/284 (0.00%) 
Salmonellosis  1  1/283 (0.35%)  0/284 (0.00%) 
Sepsis  1  2/283 (0.71%)  2/284 (0.70%) 
Septic shock  1  2/283 (0.71%)  1/284 (0.35%) 
Soft tissue infection  1  0/283 (0.00%)  1/284 (0.35%) 
Tracheobronchitis  1  0/283 (0.00%)  1/284 (0.35%) 
Upper respiratory tract infection  1  2/283 (0.71%)  1/284 (0.35%) 
Urinary tract infection  1  0/283 (0.00%)  4/284 (1.41%) 
Varicella  1  1/283 (0.35%)  0/284 (0.00%) 
Injury, poisoning and procedural complications     
Craniofacial fracture  1  0/283 (0.00%)  1/284 (0.35%) 
Femur fracture  1  0/283 (0.00%)  1/284 (0.35%) 
Infusion related reaction  1  1/283 (0.35%)  3/284 (1.06%) 
Lower limb fracture  1  1/283 (0.35%)  0/284 (0.00%) 
Lumbar vertebral fracture  1  1/283 (0.35%)  0/284 (0.00%) 
Procedural headache  1  1/283 (0.35%)  0/284 (0.00%) 
Procedural nausea  1  1/283 (0.35%)  0/284 (0.00%) 
Procedural vomiting  1  1/283 (0.35%)  0/284 (0.00%) 
Spinal compression fracture  1  1/283 (0.35%)  1/284 (0.35%) 
Spinal fracture  1  0/283 (0.00%)  1/284 (0.35%) 
Traumatic intracranial haemorrhage  1  0/283 (0.00%)  1/284 (0.35%) 
Investigations     
Neutrophil count decreased  1  0/283 (0.00%)  2/284 (0.70%) 
Platelet count decreased  1  0/283 (0.00%)  1/284 (0.35%) 
White blood cell count decreased  1  1/283 (0.35%)  0/284 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/283 (0.00%)  2/284 (0.70%) 
Electrolyte imbalance  1  1/283 (0.35%)  0/284 (0.00%) 
Hypercalcaemia  1  2/283 (0.71%)  0/284 (0.00%) 
Hyperglycaemia  1  1/283 (0.35%)  1/284 (0.35%) 
Hypokalaemia  1  0/283 (0.00%)  1/284 (0.35%) 
Hyponatraemia  1  1/283 (0.35%)  0/284 (0.00%) 
Tumour lysis syndrome  1  1/283 (0.35%)  1/284 (0.35%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/283 (0.35%)  1/284 (0.35%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder transitional cell carcinoma  1  0/283 (0.00%)  1/284 (0.35%) 
Central nervous system lymphoma  1  1/283 (0.35%)  0/284 (0.00%) 
Diffuse large B-cell lymphoma  1  3/283 (1.06%)  0/284 (0.00%) 
Lung adenocarcinoma  1  0/283 (0.00%)  1/284 (0.35%) 
Malignant melanoma in situ  1  1/283 (0.35%)  0/284 (0.00%) 
Tumour haemorrhage  1  0/283 (0.00%)  1/284 (0.35%) 
Nervous system disorders     
Altered state of consciousness  1  1/283 (0.35%)  0/284 (0.00%) 
Amnesia  1  1/283 (0.35%)  0/284 (0.00%) 
Aphasia  1  1/283 (0.35%)  0/284 (0.00%) 
Cerebrovascular accident  1  0/283 (0.00%)  2/284 (0.70%) 
Cognitive disorder  1  1/283 (0.35%)  0/284 (0.00%) 
Dizziness  1  1/283 (0.35%)  0/284 (0.00%) 
Dysarthria  1  1/283 (0.35%)  0/284 (0.00%) 
Epilepsy  1  1/283 (0.35%)  0/284 (0.00%) 
Guillain-Barre syndrome  1  0/283 (0.00%)  1/284 (0.35%) 
Haemorrhage intracranial  1  0/283 (0.00%)  1/284 (0.35%) 
Hemiparesis  1  1/283 (0.35%)  2/284 (0.70%) 
Lethargy  1  0/283 (0.00%)  1/284 (0.35%) 
Memory impairment  1  1/283 (0.35%)  0/284 (0.00%) 
Nervous system disorder  1  1/283 (0.35%)  0/284 (0.00%) 
Neuralgia  1  0/283 (0.00%)  1/284 (0.35%) 
Presyncope  1  1/283 (0.35%)  0/284 (0.00%) 
Syncope  1  2/283 (0.71%)  2/284 (0.70%) 
Vocal cord paralysis  1  1/283 (0.35%)  0/284 (0.00%) 
Psychiatric disorders     
Confusional state  1  1/283 (0.35%)  0/284 (0.00%) 
Psychotic disorder  1  1/283 (0.35%)  0/284 (0.00%) 
Tic  1  0/283 (0.00%)  1/284 (0.35%) 
Renal and urinary disorders     
Acute kidney injury  1  2/283 (0.71%)  1/284 (0.35%) 
Urinary retention  1  1/283 (0.35%)  0/284 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/283 (0.00%)  1/284 (0.35%) 
Cough  1  1/283 (0.35%)  0/284 (0.00%) 
Dyspnoea  1  0/283 (0.00%)  2/284 (0.70%) 
Interstitial lung disease  1  1/283 (0.35%)  4/284 (1.41%) 
Pleural effusion  1  1/283 (0.35%)  0/284 (0.00%) 
Pleuritic pain  1  1/283 (0.35%)  0/284 (0.00%) 
Pneumonitis  1  0/283 (0.00%)  1/284 (0.35%) 
Pulmonary embolism  1  5/283 (1.77%)  3/284 (1.06%) 
Pulmonary oedema  1  0/283 (0.00%)  2/284 (0.70%) 
Respiratory failure  1  1/283 (0.35%)  3/284 (1.06%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  1/283 (0.35%)  0/284 (0.00%) 
Drug eruption  1  1/283 (0.35%)  0/284 (0.00%) 
Rash generalised  1  1/283 (0.35%)  0/284 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  2/283 (0.71%)  1/284 (0.35%) 
Hypertension  1  1/283 (0.35%)  1/284 (0.35%) 
Hypotension  1  0/283 (0.00%)  1/284 (0.35%) 
Jugular vein thrombosis  1  1/283 (0.35%)  0/284 (0.00%) 
Thrombophlebitis superficial  1  0/283 (0.00%)  1/284 (0.35%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lenalidomide Plus R-CHOP (R2-CHOP) Placebo Plus R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   272/283 (96.11%)   270/284 (95.07%) 
Blood and lymphatic system disorders     
Anaemia  1  127/283 (44.88%)  95/284 (33.45%) 
Leukopenia  1  50/283 (17.67%)  50/284 (17.61%) 
Lymphopenia  1  35/283 (12.37%)  31/284 (10.92%) 
Neutropenia  1  183/283 (64.66%)  150/284 (52.82%) 
Thrombocytopenia  1  68/283 (24.03%)  55/284 (19.37%) 
Gastrointestinal disorders     
Abdominal pain  1  18/283 (6.36%)  16/284 (5.63%) 
Abdominal pain upper  1  11/283 (3.89%)  18/284 (6.34%) 
Constipation  1  92/283 (32.51%)  81/284 (28.52%) 
Diarrhoea  1  49/283 (17.31%)  40/284 (14.08%) 
Nausea  1  64/283 (22.61%)  66/284 (23.24%) 
Stomatitis  1  33/283 (11.66%)  37/284 (13.03%) 
Vomiting  1  32/283 (11.31%)  26/284 (9.15%) 
General disorders     
Asthenia  1  39/283 (13.78%)  28/284 (9.86%) 
Fatigue  1  40/283 (14.13%)  50/284 (17.61%) 
Oedema peripheral  1  33/283 (11.66%)  32/284 (11.27%) 
Pyrexia  1  52/283 (18.37%)  40/284 (14.08%) 
Infections and infestations     
Upper respiratory tract infection  1  23/283 (8.13%)  18/284 (6.34%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  27/283 (9.54%)  30/284 (10.56%) 
Investigations     
Alanine aminotransferase increased  1  32/283 (11.31%)  27/284 (9.51%) 
Aspartate aminotransferase increased  1  22/283 (7.77%)  20/284 (7.04%) 
Lymphocyte count decreased  1  16/283 (5.65%)  12/284 (4.23%) 
Platelet count decreased  1  21/283 (7.42%)  10/284 (3.52%) 
Weight decreased  1  21/283 (7.42%)  10/284 (3.52%) 
White blood cell count decreased  1  35/283 (12.37%)  19/284 (6.69%) 
Metabolism and nutrition disorders     
Decreased appetite  1  29/283 (10.25%)  32/284 (11.27%) 
Hyperglycaemia  1  18/283 (6.36%)  19/284 (6.69%) 
Hypokalaemia  1  41/283 (14.49%)  28/284 (9.86%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  18/283 (6.36%)  13/284 (4.58%) 
Back pain  1  15/283 (5.30%)  22/284 (7.75%) 
Nervous system disorders     
Dizziness  1  16/283 (5.65%)  16/284 (5.63%) 
Dysgeusia  1  13/283 (4.59%)  16/284 (5.63%) 
Headache  1  26/283 (9.19%)  28/284 (9.86%) 
Neuropathy peripheral  1  19/283 (6.71%)  12/284 (4.23%) 
Paraesthesia  1  25/283 (8.83%)  27/284 (9.51%) 
Peripheral sensory neuropathy  1  51/283 (18.02%)  51/284 (17.96%) 
Psychiatric disorders     
Insomnia  1  23/283 (8.13%)  32/284 (11.27%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  31/283 (10.95%)  20/284 (7.04%) 
Dyspnoea  1  12/283 (4.24%)  15/284 (5.28%) 
Oropharyngeal pain  1  16/283 (5.65%)  10/284 (3.52%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  48/283 (16.96%)  43/284 (15.14%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: ClinicalTrialDisclosure@Celgene.com
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02285062    
Other Study ID Numbers: CC-5013-DLC-002
2013-004054-21 ( EudraCT Number )
First Submitted: November 4, 2014
First Posted: November 6, 2014
Results First Submitted: March 13, 2020
Results First Posted: March 30, 2020
Last Update Posted: March 31, 2020