ROBUST: 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

• Sponsor: Celgene (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02285062
• Collaborator: (none)
• Enrollment: 570
• Locations: 282
• Arms: 2
• Anticipated Duration (Months): 90.2
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in patients who have previously untreated ABC type DLBCL.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large B-Cell, Diffuse	Drug: lenalidomide; Drug: Placebo; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: prednisone; Drug: vincristine	Phase 3

Detailed Description

This research study is for patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL) of the activated B-cell (ABC) type who have not yet been treated. DLBCL is a cancer of a type of blood cell called B-lymphocytes. B lymphocytes are part of the body's immune system. There are different types of DLBCL. About a third of newly diagnosed DLBCL cancers are the ABC type. It has been observed that treatment does not work as well for patients with the ABC type compared to patients with other DLBCL types who receive standard treatment. However, at this time both ABC type and other DLBCL type patients receive the same standard treatments.

Patients with DLBCL who are otherwise healthy are usually treated first with the chemotherapy drug combination called R-CHOP. The drugs in this combination are "R" for rituximab, "C" for cyclophosphamide, "H" for doxorubicin which has a chemical name of hydroxydaunomycin, "O" for vincristine which has a trade name of oncovin, and "P" for prednisone. Depending on the local practice where you are treated, R-CHOP may be given for 6 or 8 cycles. A cycle could lasts for 14 or 21 days. The R-CHOP drug combination is approved for the treatment of DLBCL of all types, including ABC type. R-CHOP is standard care.

This study will test the standard R-CHOP21 against R-CHOP21 plus lenalidomide. The purpose is to see whether adding lenalidomide works better and is as safe as R-CHOP by itself. This study is only for patients with ABC type DLBCL who have not yet been treated. Lenalidomide is not approved for use in DLBCL. Its use in this disease is experimental. In this study, the experimental treatment is lenalidomide + R-CHOP21 x 6.

This study will use a gene expression profile (GEP) test to see if a patient has the ABC type. The results of this GEP test affect whether you may be treated on this study. Because the performance of this test has not been proven, it is for investigational use only, and is still under development. This means the GEP test is an experimental test.

Study Design

• Study Type: Interventional
• Actual Enrollment: 570 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 3 Randomized, Double-Blind, Placebo Controlled, Multicenter Study to Compare the Efficacy and Safety of Lenalidomide (CC-5013) Plus R-CHOP Chemotherapy (R2-CHOP) Versus Placebo Plus R-CHOP Chemotherapy in Subjects With Previously Untreated Activated B-cell Type Diffuse Large B-cell Lymphoma
• Actual Study Start Date: Jan 21, 2015
• Actual Primary Completion Date: Mar 15, 2019
• Anticipated Study Completion Date: Jul 28, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R2-CHOP Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)	Drug: lenalidomide; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: prednisone; Drug: vincristine
Active Comparator: R-CHOP Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)	Drug: Placebo; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: prednisone; Drug: vincristine

Outcome Measures

Primary Outcome Measures

1. Kaplan-Meier Estimate of Progression Free Survival (PFS) [From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months]

   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.

Secondary Outcome Measures

1. Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS) [From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months]

   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.

2. K-M Estimate of Overall Survival (OS) [From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months]

   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.

3. Percentage of Participants Who Achieved a Complete Response (CR) [From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months]

   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.

4. Percentage of Participants Who Achieved an Objective Response [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]

   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.

5. K-M Estimate of Duration of Complete Response [From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months.]

   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.

6. K-M Estimate of Time to Next Lymphoma Therapy (TTNLT) [From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months]

   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.

7. Number of Participants With a Treatment Emergent Adverse Event (TEAE) [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]

   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

8. Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire [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]

   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.

9. Percentage of Participants Who Completed the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Health Related Quality of Life (HR-QoL) Questionnaire [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]

   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'.

10. Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale [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]

    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.

11. Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale [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]

    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.

12. Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale [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]

    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.

13. Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI) [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]

    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.

14. Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score [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]

    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').

15. Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS) [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]

    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".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically proven Diffuse Large B-Cell Lymphoma of the Activated B-Cell type

2. Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma

3. Measurable Diffuse Large B-Cell Lymphoma disease by Computed Tomography (CT) / Magnetic Resonance Imagining (MRI) scans

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

5. Age 18 - 80 years; age > 80 allowed at investigator discretion if performance status ≤ 1; and each organ system score ≤ 2 using cumulative illness rating scale (CIRS)

Exclusion Criteria:

1. Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma

2. History of malignancies, other than Diffuse Large B-Cell Lymphoma, unless the patient has been disease free for 5 years or more

3. Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)

4. Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF (Left Ventricular Ejection Fraction) < 45% or peripheral neuropathy grade 2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	John Muir Health	Concord	California	United States	94520
3	California Cancer Associates for Research and Excellence cCARE	Encinitas	California	United States	92024
4	Moores UCSD Cancer Center MC-0987	La Jolla	California	United States	92093
5	University of Southern California	Los Angeles	California	United States	90033
6	University of Californai, Irvine	Orange	California	United States	92868
7	UC Davis Cancer Center	Sacramento	California	United States	95817
8	Memorial Hospital	Colorado Springs	Colorado	United States	80909
9	Yale Cancer Center	New Haven	Connecticut	United States	06510
10	Memorial Healthcare System	Hollywood	Florida	United States	33021
11	John B Amos Cancer Center	Columbus	Georgia	United States	31904
12	Cancer Treatment Centers of America - Southeastern Regional Medical Center	Newnan	Georgia	United States	30265
13	University of Illinois at Chicago	Chicago	Illinois	United States	69392
14	McFarland Clinic	Ames	Iowa	United States	50010-3014
15	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101-1733
16	University of Kansas Cancer Center	Fairway	Kansas	United States	66205
17	Hematology-Oncology Clinic	Baton Rouge	Louisiana	United States	70809
18	Cancer Center of Acadiana	Lafayette	Louisiana	United States	70503
19	West Jefferson Medical Center	Marrero	Louisiana	United States	70072
20	Willis Knighton Medical Center	Shreveport	Louisiana	United States	71103
21	Center For Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
22	Maryland Oncology Hematology PA	Columbia	Maryland	United States	21044
23	Associates of Oncology/Hematology, P.C.	Rockville	Maryland	United States	20850
24	Saint Joseph Medical Center	Westminster	Maryland	United States	21157
25	St. Joseph Mercy Hosp	Ann Arbor	Michigan	United States	48106
26	Karmanos Cancer Institute	Detroit	Michigan	United States	48201-2014
27	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55416
28	University of Minnesota	Minneapolis	Minnesota	United States	55455
29	Mayo Clinic	Rochester	Minnesota	United States	55905
30	St. Louis Cancer Care LLP	Bridgeton	Missouri	United States	63044
31	Saint Louis Univ Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
32	Regional Cancer Care Associates/Cherry Hill Division, LLC.	Cherry Hill	New Jersey	United States	08003
33	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
34	Carol G Simon Cancer Center	Morristown	New Jersey	United States	07962
35	Regional Cancer Care Associates - Somerset Division	Somerville	New Jersey	United States	08876
36	Queens Medical Associates PC	Fresh Meadows	New York	United States	11366
37	Columbia University Medical Center	New York	New York	United States	10019
38	Duke University Medical Center	Durham	North Carolina	United States	27710
39	Firsthealth of The Carolinas	Pinehurst	North Carolina	United States	28374
40	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania	United States	18015
41	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
42	Bon Secours Saint Francis Health System	Greenville	South Carolina	United States	29607
43	Texas Oncology-Arlington South	Arlington	Texas	United States	76014
44	Parkland Health and Hospital Systems	Dallas	Texas	United States	75235
45	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-9068
46	Baylor College of Medicine	Houston	Texas	United States	77030
47	Houston Methodist Cancer Center	Houston	Texas	United States	77030
48	Millennium Oncology	Houston	Texas	United States	77090
49	Utah Cancer Specialist	Salt Lake City	Utah	United States	84106
50	Virginia Cancer Institute	Richmond	Virginia	United States	23230
51	VCU Massey Cancer Center	Richmond	Virginia	United States	23298-0037
52	Swedish Cancer Institute Edmonds Campus	Edmonds	Washington	United States	98026
53	Swedish Medical Center	Issaquah	Washington	United States	98029
54	Virginia Mason Medical Center	Seattle	Washington	United States	98101
55	Swedish Cancer Institute	Seattle	Washington	United States	98104
56	Swedish Cancer Institute Ballard Campus	Seattle	Washington	United States	98107
57	Medical Oncology Associates	Spokane	Washington	United States	99208
58	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
59	Albury Wodonga Regional Cancer Centre	Albury	New South Wales	Australia	2640
60	Shoalhaven Cancer Care Centre	Nowra	New South Wales	Australia	2541
61	Bendigo Hosp	Bendigo	Victoria	Australia	3550
62	Monash Medical Centre	Clayton	Victoria	Australia	3168
63	Geelong Hospital	Geelong	Victoria	Australia	3220
64	St Vincents Hospital Melbourne	Fitzroy		Australia	3065
65	Frankston Hospital	Frankston		Australia	3199
66	Austin Hospital	Heidelberg		Australia	3084
67	Royal Melbourne Hospital	Parkville		Australia	3050
68	Wellington Hospital	Wellington		Australia	6021
69	Westmead Hospital	Westmead		Australia	NSW 2145
70	Wollongong Hospital	Wollongong		Australia	2500
71	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
72	Centre Hospitalier Universitaire de Liege	Liege		Belgium	4000
73	H. Hartziekenhuis Roeselare-Menen vzw campus Wilgenstraat	Roeselare		Belgium	8800
74	AZ Nikolaas	Sint-Niklaas		Belgium	9100
75	Regionaal Ziekenhuis Jan Yperman VZW	West-Vlaanderen		Belgium	8900
76	GZA St. Augustinus	Wilrijk		Belgium	2610
77	Cliniques Universitaires UCL de Mont-Godine	Yvoir		Belgium	5530
78	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N4N2
79	Fraser Health Authority	Surrey	British Columbia	Canada	V3T 0H1
80	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 3L6
81	Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
82	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
83	Centre Hospitalier Universitaire de Sherbrooke CHUS	Greenfield Park	Quebec	Canada	J4V 2H1
84	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
85	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S7N 4H4
86	Beijing Cancer Hospital	Beijing, PR		China	100142
87	Peking University People's Hospital	Beijing		China	100044
88	Peking University Third Hospital	Beijing		China	100191
89	Peking Union Medical College Hospital	Beijing		China	100730
90	First Hospital of Jilin University	Changchun		China	130021
91	West China Medical School West China Hospital Sichuan University	Chengdu		China	610041
92	Xinqiao Hospital, Third Military Medical University	Chongqing		China	400037
93	Fujian Medical University Union Hospital	Fuzhou		China	350001
94	Guangdong General Hospital	Guangzhou, Guangdong		China	510080
95	Sun Yat-sen University Cancer Center	Guangzhou		China	510060
96	Nanfang Hospital of Southern medicine university in Guangzhou	Guangzhou		China	510515
97	First Affiliated Hospital	Hangzhou		China	310003
98	Harbin Medical University Tumor Hospital	Harbin, Heilongjiang		China	150081
99	Jiangsu Cancer Hospital	Nanjing, Jiangsu		China	210009
100	Jiangsu Province Hospital	Nanjing		China	210029
101	Fudan University Shanghai Cancer Center	Shanghai		China	200032
102	First Affiliated Hospital of Soochow University	Suzhu		China	215006
103	Tianjin Medical University Cancer Institute and Hospital	Tianjin		China	300060
104	Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology	Wuhan		China	430030
105	Fakultni Nemocnice Brno	Brno		Czechia	625 00
106	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
107	Fakultni nemocnice Olomouc	Olomouc		Czechia	775 20
108	Fakultni nemocnice Kralovske Vinohrady, Interni hematologicka klinika	Prague 10		Czechia	100 34
109	Vseobecna Fakultni Nemocnice v Praze	Praha		Czechia	128 08
110	Centre Hospitalier de la cote basque	Bayonne		France	64109
111	Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux		France	33076
112	CHRU de Brest - Hopital Morvan	Brest Cedex		France	29609
113	Hopital Henri Mondor	Creteil		France	94010
114	Centre Hospitalier Departemental de Vendee	La Roche -Sur-Yon - Cedex 9		France	85925
115	CHU Hopital Saint Eloi	Montepellier Cedex 5		France	34295
116	Hotel Dieu	Nantes		France	44093
117	Hopital Necker	Paris Cedex 15		France	75015
118	Hopital Saint Louis	Paris		France	75010
119	Hopital Haut Leveque	Pessac Cedex		France	33604
120	Centre Hospitalier D'annecy	Pringy		France	74374
121	CHRU Rennes	Rennes		France	35033
122	Centre Hospitalier de Saint Brieuc Hopital Yves le Foll	ST-Brieuc cedex 1		France	22027
123	Centre Hospitalier Universitaire de Toulouse	Toulose		France	31059
124	CHU de Nancy-Hopital Brabois Adulte	Vandoeuvre les Nancy		France	54511
125	Institut Gustave Roussy	Villejuif CEDEX		France	94805
126	Cork University Hospital	Wilton	Cork	Ireland
127	St Vincent's University Hospital	Dublin 4		Ireland	4
128	St James's Hospital	Dublin 8		Ireland	8
129	Mater Misericordiae University Hospital	Dublin		Ireland	Dublin 7
130	Mater Private Hospital	Dublin		Ireland	Dublin 7
131	University College Hospital Galway	Galway		Ireland	ST46QG
132	The Soroka University Medical Center	Beer-Sheva		Israel	84101
133	Rambam Medical Center	Haifa		Israel	31096
134	Shaare Zedek Medical Center	Jerusalem		Israel	91031
135	Hadassah Medical Center	Jerusalem		Israel	91120
136	Meir Medical Center	Kfar-Saba		Israel	44281
137	Rabin Medical Center	Petach Tikva		Israel	49100
138	Chaim Sheba Medical Center	Ramat Gan		Israel	52621
139	Assuta Medical Centers	Tel Aviv		Israel	69710
140	Tel-Aviv Sourasky Medical Center	Tel-Aviv		Israel	64239
141	Assaf Harofeh Medical Center	Zerifin		Israel	70300
142	Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo	Allessandria		Italy	15100
143	Azienda Ospedaliero Universitaria Ospedali	Ancona		Italy	60126
144	Centro di Riferimento Oncologico	Aviano		Italy	33081
145	Azienda Ospedaliera Poloclinico di Bari	Bari		Italy	70124
146	Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi	Bologna		Italy	40138
147	Spedali Civili Di Brescia	Brescia		Italy	25123
148	Ospedale Ferrarotto	Catania		Italy	95124
149	Azienda Sanitaria Ospedaliera S. Croce e Carle	Cuneo		Italy	12100
150	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50134
151	Azienda Ospedaliera Universitaria San Martino	Genova		Italy	16132
152	Ospedale Civile di Ivrea	Ivrea		Italy	10015
153	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)	Meldola		Italy	47014
154	Ospedale San Raffaele S.r.l.	Milano		Italy	20132
155	Istituto Nazionale Dei Tumori	Milano		Italy	20133
156	Azienda Ospedaliera Niguarda Ca Granda	Milano		Italy	20162
157	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena		Italy	41100
158	Azienda Ospedaliera Universitaria Federico II	Napoli, Campania		Italy	80131
159	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Napoli, Campania		Italy	80131
160	A.O.U. Maggiore della Carità	Novara		Italy	28100
161	AOU San Luigi Gonzaga	Orbassano (TO)		Italy	10043
162	Hospital of Di Padova	Padova		Italy	35128
163	Presidio Ospedaliero Andrea Tortora	Pagani		Italy	84016
164	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
165	Ospedale Civile Spirito Santo	Pescara		Italy	65124
166	Azienda Sanitaria Locale di Ravenna	Ravenna		Italy	48121
167	Azienda Ospedaliera Bianchi-Melacrino-Morelli	Reggio Calabria		Italy	89100
168	Arcispedale Santa Maria Nuova	Reggio Emilia		Italy	42100
169	Ospedale degli Infermi di Rimini	Rimini		Italy	47900
170	Policlinico Umberto I	Roma		Italy	00161
171	Azienda Ospedaliera Sant Andrea	Roma		Italy	00189
172	Policlinico Universitario Campus Biomedico Di Roma	Roma		Italy	128
173	Azienda Ospedaliera San Camillo Forlanini	Rome		Italy	00152
174	Istituto Clinico Humanitas	Rozzano (MI)		Italy	20089
175	Azienda Ospedaliera Universitaria Senese	Siena		Italy	53100
176	Azienda Ospedaliera S Maria di Terni	Terni		Italy	05100
177	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino		Italy	10126
178	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino		Italy	O1012
179	Presidio Ospedaliero Di Treviso Ca' Foncello	Treviso		Italy	31100
180	Azienda Ospedaliera Cardinale G Panico	Tricase		Italy	73039
181	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine	Udine		Italy	33100
182	Azienda Ospedaliera Universitaria Integrata di Verona	Verona		Italy	37134
183	Azienda ULSS 6 Vicenza	Vicenza		Italy	36100
184	Akita University Hospital	Akita-shi		Japan	010-8543
185	National Cancer Center Hospital	Chuo-ku		Japan	104-0045
186	Kyushu University Hospital	Fukuoka		Japan	812-8582
187	Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital	Fukuyama		Japan	720-0001
188	Tokai University School of Medicine	Isehara City, Kanagawa		Japan	259-1193
189	National Cancer Center Hospital East	Kashiwa		Japan	277-8577
190	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Koto-ku		Japan	135-8550
191	University Hospital, Kyoto Prefectural University of Medicine	Kyoto-City		Japan	602-8566
192	National Hospital Organization Kyushu Cancer Center	Minami-Ku, Fukuoka		Japan	811-1347
193	Toranomon Hospital	Minato-ku		Japan	105-8470
194	Aichi Cancer Center	Nagoya		Japan	464-8681
195	Kochi Medical School Hospital	Nankoku-shi		Japan	783-8505
196	Sendai Medical Center	Sendai-city		Japan	983-8520
197	Ehime University Hospital	Toon		Japan	791-0295
198	Yamagata University Hospital	Yamagata		Japan	990-9585
199	National Cancer Center	Gyeonggi-do		Korea, Republic of	410-769
200	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	120-752
201	Samsung Medical Center	Seoul		Korea, Republic of	135-710
202	Seoul St Marys Hospital College of Medicine The Catholic University of Korea	Seoul		Korea, Republic of	137-701
203	Asan Medical Center	Seoul		Korea, Republic of	138-736
204	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands	1066 CX
205	VU University Medical Center VU Medisch Centrum	Amsterdam		Netherlands	1081 HV
206	Amphia Ziekenhuis Molengracht	Breda		Netherlands	4818 CK
207	HagaZiekenhuis	Den Haag		Netherlands	2545 CH
208	Spaarne Ziekenhuis	Hoofddorp		Netherlands	2135
209	Medisch Centrum Leeuwarden	Leeuwarden		Netherlands	8934 AD
210	Maasstad Ziekenhuis	Rotterdam		Netherlands	3079 DZ
211	Jeroen Bosch Ziekenhuis	s-Hertogenbosch		Netherlands	5223 GZ
212	Vlietland Ziekenhuis	Schiedam		Netherlands	3118 JH
213	St. Elisabeth Ziekenhuis	Tilburg		Netherlands	5022 GC
214	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands
215	Auckland City Hospital	Auckland		New Zealand	1023
216	Canterbury Health Laboratories	Christchurch		New Zealand	8011
217	Palmerston North Hospital	Palmerston		New Zealand	4414
218	Szpital Morski im. PCK	Gdynia		Poland	81-519
219	Malopolskie Centrum Medyczne S.C.	Kraków		Poland	30-510
220	Zaklad Opieki Zdrowotnej MSW z Warminsko-Mazurskim Centrum Onkologii	Olsztyn		Poland	10-228
221	Samodz.Pub.Zaklad Opieki Zdrow-ej Min-wa Spraw Wewnetrznych w Poznaniu im Prof.Ludwika Bierkowskiego	Poznan		Poland	60-631
222	Wojskowy Instytut Medyczny	Warszawa		Poland	00-909
223	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw		Poland	50-367
224	Centro Hospitalar E Universitario de Coimbra EPE	Coimbra		Portugal	3000-075
225	Hospital Distrital Da Figueira Da Foz	Figueira da Foz		Portugal	3094-001
226	Instituto Portugues de Oncologia de Lisboa, Francisco Gentil	Lisboa		Portugal	1099-023
227	Champalimaud Cancer Center	Lisboa		Portugal	1400-038
228	Centro Hospitalar do Porto - Hospital de Santo António	Porto		Portugal	4099-001
229	Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe	Porto		Portugal	4200-072
230	Hospital Garcia de Orta	Pragal		Portugal	2801-951
231	Auxilio Mutuo Cancer Center	San Juan		Puerto Rico	00918
232	Tatarstan Republican Oncology Center	Kazan		Russian Federation	420029
233	Russian Cancer Research Center n.a. Blokhin, Chemotherapy Department	Moscow		Russian Federation	115478
234	Research Oncology Institute of Rosmed Technologies n.a. prof. N.N. Petrov	St. Petersburg		Russian Federation	197758
235	Hospital del Mar	Barcelona		Spain	08003
236	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
237	Hospital Vall d'Hebron	Barcelona		Spain	08035
238	Hospital Clinic de Barcelona	Barcelona		Spain	08036
239	Hospital Universitario Germans Trias i Pujol	Barcelona		Spain	08916
240	Hospital de San Pedro de Alcantara	Caceres		Spain	10003
241	Hospital Universitario de Canarias	La Laguna		Spain	38320
242	Hospital Universitario de la Princessa	Madrid		Spain	28006
243	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
244	Hospital Universitario Infanta Leonor	Madrid		Spain	28031
245	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
246	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
247	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
248	Hospital Universitario La Paz	Madrid		Spain	28046
249	Hospital Universitario Madrid Sanchinarro	Madrid		Spain	28050
250	Hospital Costa del Sol	Marbella		Spain	29603
251	Hospital Universitario Central de Asturias	Oviedo		Spain	33006
252	Hospital Son Llatzer	Palma de Mallorca		Spain	7198
253	Complejo Hospitalario de Navarra	Pamplona/ Navarra		Spain	31008
254	Clinica Universitaria de Navarra	Pamplona		Spain	31008
255	Hospital Universitario de Salamanca	Salamanca		Spain	37007
256	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela		Spain	15706
257	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
258	Hospital Virgen del Rocio	Sevilla		Spain	41013
259	Complejo Hospitalario Nuestra Senora de Valme	Sevilla		Spain	41014
260	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
261	Hospital Universitario Doctor Peset	Valencia		Spain	46017
262	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
263	Kantonsspital Aarau AG	Aarau		Switzerland	5001
264	Ente Ospedaliero Cantonale	Bellinzona		Switzerland	6500
265	Hopitaux Universitaire de Geneve	Geneva		Switzerland	1211
266	Kantonsspital Winterthur	Winterthur		Switzerland	8400
267	Chang Gung Medical Foundation, Kaohsiung Memorial Hospital	Niao-Sung Hsiang Kaohsiung County		Taiwan	83301
268	Chang Gung Memorial Hospital - Chiayi	Puzi City Chiayi County		Taiwan	622
269	China Medical University Hospital	Taichung City		Taiwan	40447
270	National Taiwan University Hospital	Taipei, Zhongzheng Dist.		Taiwan	100
271	Chang Gung Medical Foundation-Linkou Branch	Taoyuan		Taiwan	333
272	Cukurova Universitesi Tip Fakultesi Balcali Hastanesi	Adana		Turkey	01330
273	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara		Turkey	06100
274	Ankara University Medical Faculty Cebeci Hospital	Ankara		Turkey	06590
275	Akdeniz University Medical Faculty	Antalya		Turkey	07058
276	Pamukkale University Medical Faculty	Denizli		Turkey	20070
277	Dicle University Medical Faculty	Diyarbakir		Turkey	21280
278	Trakya Universitesi Tip Fakultesi Hastanesi	Edirne		Turkey	22030
279	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul		Turkey	34093
280	Koc Universitesi Tip Fakultesi Amerikan Hastanesi	Istanbul		Turkey	34365
281	Dokuz Eylul University Izmir	Izmir		Turkey	35340
282	Erciyes University Kayseri	Kayseri		Turkey	38039

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Jun 12, 2019
• Statistical Analysis Plan - Feb 4, 2019

More Information

Publications

• Nowakowski GS, Chiappella A, Witzig TE, Spina M, Gascoyne RD, Zhang L, Flament J, Repici J, Vitolo U. ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma. Future Oncol. 2016 Jul;12(13):1553-63. doi: 10.2217/fon-2016-0130. Epub 2016 Apr 18.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT02285062
• Other Study ID Numbers: CC-5013-DLC-002; 2013-004054-21
• First Posted: Nov 6, 2014
• Last Update Posted: Feb 11, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Celgene: R-CHOP chemotherapy; DLBCL front line therapy; gene expression profiling (GEP) activated B-cell (ABC) type DLBCL biomarkers; Activated B-Cell (ABC) type; Diffuse Large B-Cell Lymphoma, not otherwise specified; Diffuse Large B-Cell Lymphoma, associated with chronic inflammation; Diffuse Large B-Cell Lymphoma, Epstein-Barr virus positive (EBS+) of the elderly; Diffuse Large B-Cell Lymphoma, T-cell / histiocyte-rich
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Lenalidomide

Study Results

Participant Flow

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 Detail	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
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	207	201
NOT COMPLETED	78	84

Baseline Characteristics

Arm/Group Title	Lenalidomide Plus R-CHOP (R2-CHOP)	Placebo Plus R-CHOP	Total
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 Participants	285	285	570
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.5 (11.72)	63.9 (9.35)	63.2 (10.62)
Age, Customized (Count of Participants)
< 65	138 48.4%	137 48.1%	275 48.2%
≥ 65	147 51.6%	148 51.9%	295 51.8%
Sex: Female, Male (Count of Participants)
Female	121 42.5%	142 49.8%	263 46.1%
Male	164 57.5%	143 50.2%	307 53.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 4.9%	17 6%	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 (Count of 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) (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.780 (0.2167)	1.775 (0.2101)	1.777 (0.2132)
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of 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%
Creatinine Clearance (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	92.08 (35.576)	90.19 (31.040)	91.14 (33.373)
International Prognostic Index (IPI) Score (Count of Participants)
= 2	121 42.5%	120 42.1%	241 42.3%
≥ 3	164 57.5%	165 57.9%	329 57.7%
Presence of Bulky Disease (Count of Participants)
< 7.0 cm (Non-Bulky Disease)	188 66%	186 65.3%	374 65.6%
≥ 7.0 cm (Bulky Disease)	97 34%	99 34.7%	196 34.4%
Disease Stage of Diffuse Large B-Cell Lymphoma at Diagnosis (Count of Participants)
Stage I	0 0%	1 0.4%	1 0.2%
Stage II	37 13%	32 11.2%	69 12.1%
Stage III	80 28.1%	98 34.4%	178 31.2%
Stage IV	168 58.9%	154 54%	322 56.5%

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimate of Progression Free Survival (PFS)
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2864
	Comments
	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
	Parameter Dispersion	Type: Value:
	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)
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7294
	Comments
	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
	Parameter Dispersion	Type: Value:
	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)
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6433
	Comments
	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
	Parameter Dispersion	Type: Value:
	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)
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Number (95% Confidence Interval) [Percentage of Participants]	69.1 24.2%	64.9 22.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
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

5. Secondary Outcome

Title	Percentage of Participants Who Achieved an Objective Response
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Number (95% Confidence Interval) [Percentage of Participants]	90.9 31.9%	90.9 31.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
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

6. Secondary Outcome

Title	K-M Estimate of Duration of Complete Response
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.

Outcome Measure Data

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
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.
Measure Participants	197	185
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2143
	Comments
	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
	Parameter Dispersion	Type: Value:
	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)
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide Plus R-CHOP (R2-CHOP), Placebo Plus R-CHOP
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3150
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR is derived from Cox model

8. Secondary Outcome

Title	Number of Participants With a Treatment Emergent Adverse Event (TEAE)
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

Outcome Measure Data

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
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.
Measure Participants	283	284
≥ 1 TEAE	281 98.6%	279 97.9%
≥1 TEAE Related to Lenalidomide (LEN)/Placebo	249 87.4%	222 77.9%
≥ 1 TEAE Related to RCHOP	271 95.1%	254 89.1%
≥ 1 Grade (GR) 3 TEAE	203 71.2%	172 60.4%
≥ 1 GR 4 TEAE	154 54%	129 45.3%
≥ 1 GR 3 or 4 TEAE	221 77.5%	203 71.2%
≥1 GR 3 or 4 TEAE Related to LEN/Placebo (PBO)	185 64.9%	157 55.1%
≥ 1 GR 3 or 4 TEAE related to R- CHOP	200 70.2%	177 62.1%
≥ 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 36.5%	88 30.9%
≥ 1 Treatment-Emergent SAE Related to LEN/PBO	69 24.2%	57 20%
≥1 Treatment-Emergent SAE Related to R-CHOP	67 23.5%	60 21.1%
≥1 TEAE Leading to Discontinuing (DC) LEN/PBO	49 17.2%	32 11.2%
≥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 55.8%	129 45.3%
≥1 TEAE Leading to Dose Reduction of LEN/PBO	68 23.9%	41 14.4%
≥1 TEAE Leading to Dose Interruption of LEN/PBO	144 50.5%	122 42.8%
≥1 TEAE Lead to Dose Reduction/Interruption R-CHOP	97 34%	82 28.8%
≥ 1 TEAE Leading to Dose Reduction of R-CHOP	54 18.9%	45 15.8%
≥ 1 TEAE Leading to Dose Interruption of R-CHOP	64 22.5%	53 18.6%

9. Secondary Outcome

Title	Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Screening	98.6 34.6%	98.2 34.5%
Midcycle = After Cycle 3, but before Cycle 4	87.0 30.5%	86.3 30.3%
End of Treatment (EoT) = 3-4 weeks after C6	76.1 26.7%	79.6 27.9%
Follow-Up Period: Week 34	67.7 23.8%	69.5 24.4%

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
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

Outcome Measure Data

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
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.
Measure Participants	285	285
Screening	98.9 34.7%	97.9 34.4%
Midcycle	87.0 30.5%	86.3 30.3%
End of Treatment (EoT)	76.5 26.8%	79.6 27.9%
Follow-Up Period: Week 34	68.1 23.9%	69.1 24.2%

11. Secondary Outcome

Title	Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale
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

Outcome Measure Data

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
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.
Measure Participants	257	257
Midcycle	-0.7 (5.91)	0.2 (5.40)
C6 D1	-0.0 (6.35)	0.9 (6.02)
EoT = 3-4 weeks after C6	1.5 (5.53)	0.7 (5.72)
Follow-Up Period: Week 34	2.8 (5.24)	2.6 (5.55)

12. Secondary Outcome

Title	Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale
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

Outcome Measure Data

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
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.
Measure Participants	257	255
Midcycle	3.8 (10.33)	4.1 (8.88)
C6 D1	5.8 (11.11)	5.2 (9.40)
EoT = 3-4 weeks after C6	6.6 (10.11)	4.5 (9.62)
Follow-Up Period: Week 34	8.3 (10.61)	6.5 (9.20)

13. Secondary Outcome

Title	Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale
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

Outcome Measure Data

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
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.
Measure Participants	258	256
Midcycle	-0.5 (6.12)	0.5 (5.84)
C6 D1	0.0 (6.24)	1.4 (5.63)
EoT = 3-4 weeks after C6	1.0 (6.53)	0.7 (6.71)
Follow-Up Period: Week 34	2.3 (6.65)	3.1 (6.17)

14. Secondary Outcome

Title	Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI)
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

Outcome Measure Data

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
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.
Measure Participants	256	254
Midcycle	2.6 (18.26)	4.6 (16.49)
C6 D1	5.9 (19.85)	7.5 (17.40)
EoT = 3-4 weeks after C6	9.1 (18.51)	5.8 (18.64)
Follow-Up Period: Week 34	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
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

Outcome Measure Data

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
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.
Measure Participants	257	255
Midcycle	0.08 (0.308)	0.08 (0.281)
C6 D1	0.10 (0.325)	0.14 (0.330)
EoT = 3-4 weeks after C6	0.10 (0.309)	0.06 (0.319)
Follow-Up Period: Week 34	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)
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

Outcome Measure Data

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
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.
Measure Participants	256	255
Midcycle	4.0 (20.5)	3.0 (18.2)
C6 D1	6.0 (23.5)	9.0 (24.5)
EoT = 3-4 weeks after C6	8.0 (18.7)	6.0 (21.5)
Follow-Up Period: Week 34	12.0 (20.2)	9 (21.4)

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	58/285 (20.4%)		62/285 (21.8%)
Serious Adverse Events
	Lenalidomide Plus R-CHOP (R2-CHOP)		Placebo Plus R-CHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/283 (36.7%)		88/284 (31%)
Blood and lymphatic system disorders
Agranulocytosis	1/283 (0.4%)		1/284 (0.4%)
Anaemia	6/283 (2.1%)		6/284 (2.1%)
Cytopenia	1/283 (0.4%)		0/284 (0%)
Febrile neutropenia	31/283 (11%)		14/284 (4.9%)
Leukopenia	2/283 (0.7%)		0/284 (0%)
Lymphadenopathy	0/283 (0%)		1/284 (0.4%)
Neutropenia	19/283 (6.7%)		13/284 (4.6%)
Splenic necrosis	0/283 (0%)		1/284 (0.4%)
Thrombocytopenia	16/283 (5.7%)		1/284 (0.4%)
Cardiac disorders
Acute coronary syndrome	1/283 (0.4%)		0/284 (0%)
Acute myocardial infarction	2/283 (0.7%)		0/284 (0%)
Arrhythmia supraventricular	1/283 (0.4%)		0/284 (0%)
Atrial fibrillation	2/283 (0.7%)		4/284 (1.4%)
Atrial flutter	0/283 (0%)		1/284 (0.4%)
Cardiac arrest	0/283 (0%)		1/284 (0.4%)
Cardiac disorder	0/283 (0%)		1/284 (0.4%)
Cardiac failure	0/283 (0%)		3/284 (1.1%)
Cardiac failure congestive	0/283 (0%)		1/284 (0.4%)
Coronary artery disease	0/283 (0%)		1/284 (0.4%)
Sinus tachycardia	0/283 (0%)		1/284 (0.4%)
Gastrointestinal disorders
Abdominal distension	1/283 (0.4%)		0/284 (0%)
Abdominal pain	4/283 (1.4%)		0/284 (0%)
Dental caries	0/283 (0%)		1/284 (0.4%)
Diarrhoea	6/283 (2.1%)		4/284 (1.4%)
Diverticular perforation	0/283 (0%)		1/284 (0.4%)
Enterocutaneous fistula	0/283 (0%)		1/284 (0.4%)
Flatulence	1/283 (0.4%)		0/284 (0%)
Gastric haemorrhage	2/283 (0.7%)		1/284 (0.4%)
Gastroduodenal haemorrhage	0/283 (0%)		1/284 (0.4%)
Gastrointestinal haemorrhage	1/283 (0.4%)		0/284 (0%)
Haematochezia	1/283 (0.4%)		0/284 (0%)
Intestinal obstruction	1/283 (0.4%)		0/284 (0%)
Large intestine perforation	0/283 (0%)		1/284 (0.4%)
Nausea	2/283 (0.7%)		2/284 (0.7%)
Neutropenic colitis	0/283 (0%)		1/284 (0.4%)
Stomatitis	2/283 (0.7%)		0/284 (0%)
Vomiting	3/283 (1.1%)		1/284 (0.4%)
General disorders
Asthenia	2/283 (0.7%)		1/284 (0.4%)
Death	1/283 (0.4%)		0/284 (0%)
Extravasation	1/283 (0.4%)		0/284 (0%)
Face oedema	1/283 (0.4%)		0/284 (0%)
General physical health deterioration	1/283 (0.4%)		0/284 (0%)
Hypothermia	1/283 (0.4%)		0/284 (0%)
Malaise	1/283 (0.4%)		0/284 (0%)
Non-cardiac chest pain	0/283 (0%)		1/284 (0.4%)
Oedema peripheral	1/283 (0.4%)		0/284 (0%)
Pyrexia	7/283 (2.5%)		9/284 (3.2%)
Sudden cardiac death	1/283 (0.4%)		0/284 (0%)
Hepatobiliary disorders
Bile duct stone	1/283 (0.4%)		0/284 (0%)
Drug-induced liver injury	1/283 (0.4%)		0/284 (0%)
Hepatic function abnormal	0/283 (0%)		1/284 (0.4%)
Hepatitis	0/283 (0%)		1/284 (0.4%)
Jaundice cholestatic	1/283 (0.4%)		0/284 (0%)
Liver injury	0/283 (0%)		1/284 (0.4%)
Immune system disorders
Contrast media allergy	0/283 (0%)		1/284 (0.4%)
Infections and infestations
Abdominal infection	0/283 (0%)		1/284 (0.4%)
Anal abscess	1/283 (0.4%)		0/284 (0%)
Appendicitis	1/283 (0.4%)		1/284 (0.4%)
Arthritis bacterial	1/283 (0.4%)		0/284 (0%)
Bacterial infection	1/283 (0.4%)		0/284 (0%)
Bronchitis	0/283 (0%)		1/284 (0.4%)
Campylobacter gastroenteritis	1/283 (0.4%)		0/284 (0%)
Cellulitis	3/283 (1.1%)		0/284 (0%)
Clostridium difficile colitis	1/283 (0.4%)		1/284 (0.4%)
Cytomegalovirus infection	1/283 (0.4%)		1/284 (0.4%)
Device related infection	1/283 (0.4%)		2/284 (0.7%)
Device related sepsis	2/283 (0.7%)		0/284 (0%)
Escherichia sepsis	1/283 (0.4%)		0/284 (0%)
Escherichia urinary tract infection	1/283 (0.4%)		0/284 (0%)
Groin abscess	1/283 (0.4%)		0/284 (0%)
Hepatitis B	0/283 (0%)		1/284 (0.4%)
Herpes zoster	0/283 (0%)		1/284 (0.4%)
Influenza	1/283 (0.4%)		0/284 (0%)
Klebsiella infection	1/283 (0.4%)		0/284 (0%)
Lower respiratory tract infection	0/283 (0%)		1/284 (0.4%)
Lower respiratory tract infection bacterial	1/283 (0.4%)		0/284 (0%)
Lung infection	4/283 (1.4%)		2/284 (0.7%)
Neutropenic sepsis	1/283 (0.4%)		0/284 (0%)
Osteomyelitis	0/283 (0%)		1/284 (0.4%)
Parainfluenzae virus infection	1/283 (0.4%)		0/284 (0%)
Pharyngitis	0/283 (0%)		1/284 (0.4%)
Pneumocystis jirovecii pneumonia	0/283 (0%)		1/284 (0.4%)
Pneumonia	11/283 (3.9%)		7/284 (2.5%)
Pulmonary sepsis	1/283 (0.4%)		0/284 (0%)
Salmonellosis	1/283 (0.4%)		0/284 (0%)
Sepsis	2/283 (0.7%)		2/284 (0.7%)
Septic shock	2/283 (0.7%)		1/284 (0.4%)
Soft tissue infection	0/283 (0%)		1/284 (0.4%)
Tracheobronchitis	0/283 (0%)		1/284 (0.4%)
Upper respiratory tract infection	2/283 (0.7%)		1/284 (0.4%)
Urinary tract infection	0/283 (0%)		4/284 (1.4%)
Varicella	1/283 (0.4%)		0/284 (0%)
Injury, poisoning and procedural complications
Craniofacial fracture	0/283 (0%)		1/284 (0.4%)
Femur fracture	0/283 (0%)		1/284 (0.4%)
Infusion related reaction	1/283 (0.4%)		3/284 (1.1%)
Lower limb fracture	1/283 (0.4%)		0/284 (0%)
Lumbar vertebral fracture	1/283 (0.4%)		0/284 (0%)
Procedural headache	1/283 (0.4%)		0/284 (0%)
Procedural nausea	1/283 (0.4%)		0/284 (0%)
Procedural vomiting	1/283 (0.4%)		0/284 (0%)
Spinal compression fracture	1/283 (0.4%)		1/284 (0.4%)
Spinal fracture	0/283 (0%)		1/284 (0.4%)
Traumatic intracranial haemorrhage	0/283 (0%)		1/284 (0.4%)
Investigations
Neutrophil count decreased	0/283 (0%)		2/284 (0.7%)
Platelet count decreased	0/283 (0%)		1/284 (0.4%)
White blood cell count decreased	1/283 (0.4%)		0/284 (0%)
Metabolism and nutrition disorders
Dehydration	0/283 (0%)		2/284 (0.7%)
Electrolyte imbalance	1/283 (0.4%)		0/284 (0%)
Hypercalcaemia	2/283 (0.7%)		0/284 (0%)
Hyperglycaemia	1/283 (0.4%)		1/284 (0.4%)
Hypokalaemia	0/283 (0%)		1/284 (0.4%)
Hyponatraemia	1/283 (0.4%)		0/284 (0%)
Tumour lysis syndrome	1/283 (0.4%)		1/284 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/283 (0.4%)		1/284 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/283 (0%)		1/284 (0.4%)
Central nervous system lymphoma	1/283 (0.4%)		0/284 (0%)
Diffuse large B-cell lymphoma	3/283 (1.1%)		0/284 (0%)
Lung adenocarcinoma	0/283 (0%)		1/284 (0.4%)
Malignant melanoma in situ	1/283 (0.4%)		0/284 (0%)
Tumour haemorrhage	0/283 (0%)		1/284 (0.4%)
Nervous system disorders
Altered state of consciousness	1/283 (0.4%)		0/284 (0%)
Amnesia	1/283 (0.4%)		0/284 (0%)
Aphasia	1/283 (0.4%)		0/284 (0%)
Cerebrovascular accident	0/283 (0%)		2/284 (0.7%)
Cognitive disorder	1/283 (0.4%)		0/284 (0%)
Dizziness	1/283 (0.4%)		0/284 (0%)
Dysarthria	1/283 (0.4%)		0/284 (0%)
Epilepsy	1/283 (0.4%)		0/284 (0%)
Guillain-Barre syndrome	0/283 (0%)		1/284 (0.4%)
Haemorrhage intracranial	0/283 (0%)		1/284 (0.4%)
Hemiparesis	1/283 (0.4%)		2/284 (0.7%)
Lethargy	0/283 (0%)		1/284 (0.4%)
Memory impairment	1/283 (0.4%)		0/284 (0%)
Nervous system disorder	1/283 (0.4%)		0/284 (0%)
Neuralgia	0/283 (0%)		1/284 (0.4%)
Presyncope	1/283 (0.4%)		0/284 (0%)
Syncope	2/283 (0.7%)		2/284 (0.7%)
Vocal cord paralysis	1/283 (0.4%)		0/284 (0%)
Psychiatric disorders
Confusional state	1/283 (0.4%)		0/284 (0%)
Psychotic disorder	1/283 (0.4%)		0/284 (0%)
Tic	0/283 (0%)		1/284 (0.4%)
Renal and urinary disorders
Acute kidney injury	2/283 (0.7%)		1/284 (0.4%)
Urinary retention	1/283 (0.4%)		0/284 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/283 (0%)		1/284 (0.4%)
Cough	1/283 (0.4%)		0/284 (0%)
Dyspnoea	0/283 (0%)		2/284 (0.7%)
Interstitial lung disease	1/283 (0.4%)		4/284 (1.4%)
Pleural effusion	1/283 (0.4%)		0/284 (0%)
Pleuritic pain	1/283 (0.4%)		0/284 (0%)
Pneumonitis	0/283 (0%)		1/284 (0.4%)
Pulmonary embolism	5/283 (1.8%)		3/284 (1.1%)
Pulmonary oedema	0/283 (0%)		2/284 (0.7%)
Respiratory failure	1/283 (0.4%)		3/284 (1.1%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/283 (0.4%)		0/284 (0%)
Drug eruption	1/283 (0.4%)		0/284 (0%)
Rash generalised	1/283 (0.4%)		0/284 (0%)
Vascular disorders
Deep vein thrombosis	2/283 (0.7%)		1/284 (0.4%)
Hypertension	1/283 (0.4%)		1/284 (0.4%)
Hypotension	0/283 (0%)		1/284 (0.4%)
Jugular vein thrombosis	1/283 (0.4%)		0/284 (0%)
Thrombophlebitis superficial	0/283 (0%)		1/284 (0.4%)
Other (Not Including Serious) Adverse Events
	Lenalidomide Plus R-CHOP (R2-CHOP)		Placebo Plus R-CHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	272/283 (96.1%)		270/284 (95.1%)
Blood and lymphatic system disorders
Anaemia	127/283 (44.9%)		95/284 (33.5%)
Leukopenia	50/283 (17.7%)		50/284 (17.6%)
Lymphopenia	35/283 (12.4%)		31/284 (10.9%)
Neutropenia	183/283 (64.7%)		150/284 (52.8%)
Thrombocytopenia	68/283 (24%)		55/284 (19.4%)
Gastrointestinal disorders
Abdominal pain	18/283 (6.4%)		16/284 (5.6%)
Abdominal pain upper	11/283 (3.9%)		18/284 (6.3%)
Constipation	92/283 (32.5%)		81/284 (28.5%)
Diarrhoea	49/283 (17.3%)		40/284 (14.1%)
Nausea	64/283 (22.6%)		66/284 (23.2%)
Stomatitis	33/283 (11.7%)		37/284 (13%)
Vomiting	32/283 (11.3%)		26/284 (9.2%)
General disorders
Asthenia	39/283 (13.8%)		28/284 (9.9%)
Fatigue	40/283 (14.1%)		50/284 (17.6%)
Oedema peripheral	33/283 (11.7%)		32/284 (11.3%)
Pyrexia	52/283 (18.4%)		40/284 (14.1%)
Infections and infestations
Upper respiratory tract infection	23/283 (8.1%)		18/284 (6.3%)
Injury, poisoning and procedural complications
Infusion related reaction	27/283 (9.5%)		30/284 (10.6%)
Investigations
Alanine aminotransferase increased	32/283 (11.3%)		27/284 (9.5%)
Aspartate aminotransferase increased	22/283 (7.8%)		20/284 (7%)
Lymphocyte count decreased	16/283 (5.7%)		12/284 (4.2%)
Platelet count decreased	21/283 (7.4%)		10/284 (3.5%)
Weight decreased	21/283 (7.4%)		10/284 (3.5%)
White blood cell count decreased	35/283 (12.4%)		19/284 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	29/283 (10.2%)		32/284 (11.3%)
Hyperglycaemia	18/283 (6.4%)		19/284 (6.7%)
Hypokalaemia	41/283 (14.5%)		28/284 (9.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	18/283 (6.4%)		13/284 (4.6%)
Back pain	15/283 (5.3%)		22/284 (7.7%)
Nervous system disorders
Dizziness	16/283 (5.7%)		16/284 (5.6%)
Dysgeusia	13/283 (4.6%)		16/284 (5.6%)
Headache	26/283 (9.2%)		28/284 (9.9%)
Neuropathy peripheral	19/283 (6.7%)		12/284 (4.2%)
Paraesthesia	25/283 (8.8%)		27/284 (9.5%)
Peripheral sensory neuropathy	51/283 (18%)		51/284 (18%)
Psychiatric disorders
Insomnia	23/283 (8.1%)		32/284 (11.3%)
Respiratory, thoracic and mediastinal disorders
Cough	31/283 (11%)		20/284 (7%)
Dyspnoea	12/283 (4.2%)		15/284 (5.3%)
Oropharyngeal pain	16/283 (5.7%)		10/284 (3.5%)
Skin and subcutaneous tissue disorders
Alopecia	48/283 (17%)		43/284 (15.1%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.