Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01145495
• Collaborator: (none)
• Enrollment: 63
• Locations: 91
• Arm: 1
• Actual Duration (Months): 139
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well lenalidomide and rituximab work in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide together with rituximab may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Ann Arbor Stage III Grade 1 Follicular Lymphoma; Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage III Grade 3 Follicular Lymphoma; Ann Arbor Stage IV Grade 1 Follicular Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Grade 3 Follicular Lymphoma	Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the response rate (overall and complete) to lenalidomide + rituximab in follicular non-Hodgkin lymphoma (NHL) patients who have received no prior systemic therapy.

2. To determine the time to progression after lenalidomide + rituximab in previously untreated patients with cluster of differentiation (CD)20+ follicular NHL.

SECONDARY OBJECTIVES:

1. To determine the toxicity profile of lenalidomide + rituximab therapy in previously untreated patients with CD20+ follicular NHL.

2. To establish whether the therapeutic effects of lenalidomide + rituximab combination are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).

3. To correlate fragment crystallizable gamma (Fcg) receptor polymorphism profiling with response to lenalidomide + rituximab in previously untreated patients with follicular NHL.

4. To determine the impact of lenalidomide on immune parameters in patients with previously untreated follicular lymphoma.

5. To determine the impact of lenalidomide on angiogenic parameters in patients with previously untreated follicular lymphoma.

6. To correlate lymphoma-associated macrophages (LAM) and forkhead box P3 (FOXP3), granzyme B (GzB), CD10, multiple myeloma oncogene 1 (MUM1), and B-cell lymphoma 2 (BCL2) expression with response to rituximab + lenalidomide in previously untreated patients with follicular lymphoma.

7. Determine whether immune gene signatures previously identified as prognostic factors in follicular lymphoma (FL) can be applied to paraffin-embedded tissues in rituximab treated patients; evaluate micro ribonucleic acid (RNA) signatures associated with these gene signatures and outcome; to validate immunohistochemical markers associated with outcome in FL (CD68 LAMs, FOXP3, CD10, BCL6, FOXP1, MUM1); and investigate whether markers of angiogenesis may be of value in prognosis of FL.

OUTLINE:

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 and on weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for up to 8 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)
• Actual Study Start Date: Jun 15, 2010
• Actual Primary Completion Date: Dec 31, 2012
• Actual Study Completion Date: Jan 15, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (lenalidomide, rituximab) Patients receive lenalidomide PO QD on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 and in weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Biological: Rituximab; Given IV; Other Names: ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Riabni Rituxan Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR rituximab-abbs Rituximab-arrx Rituximab-pvvr RTXM83 Ruxience Truxima

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved a Complete Response [At 12 months]

   Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.

Secondary Outcome Measures

1. Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [Up to 10 years]

   Data will be summarized using frequency tables.

2. Time to Disease Progression [Up to 10 years]

   Kaplan-Meier method will be used.

3. Time to Best Response [Up to 10 years]

   Kaplan-Meier method will be used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any uni-dimensional measurement) stage II

• Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis

• Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation

• Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression

• Low or intermediate risk by Follicular Lymphoma International Prognostic Index (FLIPI): 0-2 risk factors

• No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy); patients may have received involved-field radiation therapy

• No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable

• Lesions that are considered non-measurable include the following:

• Bone lesions (lesions if present should be noted)

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Bone marrow (involvement by NHL should be noted)

• No known central nervous system (CNS) involvement by lymphoma

• Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following

• No evidence of coinfection with hepatitis B or C

• CD4+ cell count >= 400/mm^3

• No evidence of resistant strains of HIV

• If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL

• If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL

• No history of acquired immune deficiency syndrome (AIDS)-defining conditions

• No evidence of active hepatitis B or C infection (i.e., no positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen positive [HBsAg +]) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose

• Patients with a history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome are not eligible

• Patients with uncontrolled seizures are not eligible

• Patients with an autoimmune disorder requires active immunosuppression are not eligible

• Non-pregnant and non-nursing; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

• No known human anti-chimeric antibody (HACA) positivity

• Absolute neutrophil count (ANC) >= 1,000/microliter

• Platelet count >= 75,000/microliter

• Creatinine clearance >= 30 mL/min unless attributable to NHL; to be calculated by method of Cockcroft-Gault, using actual weight; maximum creatinine clearance (CrCl) 125 mL/min

• Total bilirubin =< 2 times upper limit of normal (ULN) unless attributable to NHL or Gilbert disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
2	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
3	Beebe Medical Center	Lewes	Delaware	United States	19958
4	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
5	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
6	AdventHealth Orlando	Orlando	Florida	United States	32803
7	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
8	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
9	Graham Hospital Association	Canton	Illinois	United States	61520
10	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
11	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
12	Memorial Hospital	Carthage	Illinois	United States	62321
13	University of Illinois	Chicago	Illinois	United States	60612
14	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
15	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
16	Eureka Hospital	Eureka	Illinois	United States	61530
17	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
18	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
19	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
20	Mason District Hospital	Havana	Illinois	United States	62644
21	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
22	AMITA Health Adventist Medical Center	La Grange	Illinois	United States	60525
23	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
24	Mcdonough District Hospital	Macomb	Illinois	United States	61455
25	Holy Family Medical Center	Monmouth	Illinois	United States	61462
26	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
27	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
28	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
29	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
30	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
31	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
32	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
33	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
34	Proctor Hospital	Peoria	Illinois	United States	61614
35	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
36	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
37	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
38	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
39	Illinois Valley Hospital	Peru	Illinois	United States	61354
40	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
41	Perry Memorial Hospital	Princeton	Illinois	United States	61356
42	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
43	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
44	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa	United States	52722
45	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
46	Eastern Maine Medical Center	Bangor	Maine	United States	04401
47	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
48	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
49	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
50	Minneapolis VA Medical Center	Minneapolis	Minnesota	United States	55417
51	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
52	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
53	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
54	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
55	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
56	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
57	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
58	Comprehensive Cancer Care PC	Saint Louis	Missouri	United States	63141
59	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
60	Great Plains Health Callahan Cancer Center	North Platte	Nebraska	United States	69101
61	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
62	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
63	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire	United States	03301
64	Exeter Hospital	Exeter	New Hampshire	United States	03833
65	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
66	Solinsky Center for Cancer Care	Manchester	New Hampshire	United States	03103
67	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
68	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
69	Glens Falls Hospital	Glens Falls	New York	United States	12801
70	Northwell Health NCORP	Lake Success	New York	United States	11042
71	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
72	North Shore University Hospital	Manhasset	New York	United States	11030
73	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
74	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
75	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
76	Randolph Hospital	Asheboro	North Carolina	United States	27203
77	Mission Hospital	Asheville	North Carolina	United States	28801
78	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
79	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
80	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
81	East Carolina University	Greenville	North Carolina	United States	27834
82	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
83	Annie Penn Memorial Hospital	Reidsville	North Carolina	United States	27320
84	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
85	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
86	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
87	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
88	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
89	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
90	Danville Regional Medical Center	Danville	Virginia	United States	24541
91	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Peter Martin, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01145495
• Other Study ID Numbers: NCI-2011-02047; NCI-2011-02047; CDR0000675161; CALGB 50803; CALGB-50803; U10CA180821; U10CA031946
• First Posted: Jun 16, 2010
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Rituximab; Antineoplastic Agents, Immunological; Lenalidomide; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Between June 2010 and November 2011, 66 participants were recruited.
Pre-assignment Detail	Three participants did not receive protocol treatment and were dropped from all analyses.

Arm/Group Title	Treatment (Lenalidomide, Rituximab)
Arm/Group Description	Patients receive oral lenalidomide (20mg) once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab (375mg/m^2) IV in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity. > > rituximab: Given IV > > lenalidomide: Given orally
Period Title: Overall Study
STARTED	63
COMPLETED	51
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Treatment (Lenalidomide, Rituximab)
Arm/Group Description	Patients receive oral lenalidomide (20mg) once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab (375mg/m^2) IV in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity. rituximab: Given IV lenalidomide: Given orally
Overall Participants	63
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	32 50.8%
Male	31 49.2%
Region of Enrollment (participants) [Number]
United States	63 100%
Follicular Lymphoma International Prognostic Index (FLIPI) (participants) [Number]
0-1	19 30.2%
2	42 66.7%
Not reported	2 3.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved a Complete Response
Description	Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

At the time of analysis, 54 participants had adequate to evaluate response.

Arm/Group Title	Treatment (Lenalidomide, Rituximab)
Arm/Group Description	Patients receive oral lenalidomide (20mg) once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab (375mg/m^2) IV in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity. rituximab: Given IV lenalidomide: Given orally
Measure Participants	54
Number [participants]	39 61.9%

2. Secondary Outcome

Title	Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description	Data will be summarized using frequency tables.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to Disease Progression
Description	Kaplan-Meier method will be used.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Best Response
Description	Kaplan-Meier method will be used.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Treatment (Lenalidomide, Rituximab)
Arm/Group Description	lenalidomide: Given orally
All Cause Mortality
	Treatment (Lenalidomide, Rituximab)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Lenalidomide, Rituximab)
	Affected / at Risk (%)	# Events
Total	15/63 (23.8%)
Blood and lymphatic system disorders
Anemia	5/63 (7.9%)	7
Leukocytosis	1/63 (1.6%)	1
Cardiac disorders
Chest pain - cardiac	1/63 (1.6%)	1
Sinus bradycardia	2/63 (3.2%)	2
Eye disorders
Photophobia	1/63 (1.6%)	1
Watering eyes	1/63 (1.6%)	1
Gastrointestinal disorders
Abdominal distension	1/63 (1.6%)	1
Abdominal pain	1/63 (1.6%)	1
Bloating	1/63 (1.6%)	1
Constipation	6/63 (9.5%)	12
Dyspepsia	2/63 (3.2%)	2
Enterocolitis	1/63 (1.6%)	1
Gastrointestinal disorders - Other	2/63 (3.2%)	2
Ileal perforation	1/63 (1.6%)	1
Mucositis oral	2/63 (3.2%)	2
Nausea	3/63 (4.8%)	6
Vomiting	2/63 (3.2%)	3
General disorders
Chills	1/63 (1.6%)	1
Edema limbs	1/63 (1.6%)	1
Fatigue	8/63 (12.7%)	13
Fever	3/63 (4.8%)	3
Infusion related reaction	2/63 (3.2%)	2
Non-cardiac chest pain	1/63 (1.6%)	1
Pain	2/63 (3.2%)	2
Immune system disorders
Allergic reaction	1/63 (1.6%)	1
Serum sickness	1/63 (1.6%)	1
Infections and infestations
Skin infection	2/63 (3.2%)	2
Urinary tract infection	1/63 (1.6%)	1
Injury, poisoning and procedural complications
Bruising	1/63 (1.6%)	1
Investigations
Activated partial thromboplastin time prolonged	1/63 (1.6%)	1
Alanine aminotransferase increased	4/63 (6.3%)	4
Alkaline phosphatase increased	1/63 (1.6%)	1
Aspartate aminotransferase increased	2/63 (3.2%)	2
Blood bilirubin increased	2/63 (3.2%)	2
Hemoglobin increased	1/63 (1.6%)	1
INR increased	1/63 (1.6%)	1
Lymphocyte count decreased	10/63 (15.9%)	13
Neutrophil count decreased	7/63 (11.1%)	8
Platelet count decreased	6/63 (9.5%)	6
White blood cell decreased	4/63 (6.3%)	4
Metabolism and nutrition disorders
Anorexia	1/63 (1.6%)	1
Dehydration	1/63 (1.6%)	1
Hyperglycemia	3/63 (4.8%)	3
Hypoalbuminemia	3/63 (4.8%)	3
Hypocalcemia	2/63 (3.2%)	2
Hypokalemia	2/63 (3.2%)	2
Hyponatremia	2/63 (3.2%)	2
Hypophosphatemia	1/63 (1.6%)	1
Tumor lysis syndrome	2/63 (3.2%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/63 (3.2%)	3
Back pain	2/63 (3.2%)	2
Generalized muscle weakness	1/63 (1.6%)	1
Myalgia	3/63 (4.8%)	4
Neck pain	1/63 (1.6%)	1
Pain in extremity	1/63 (1.6%)	1
Nervous system disorders
Dizziness	1/63 (1.6%)	1
Dysgeusia	1/63 (1.6%)	1
Headache	2/63 (3.2%)	2
Memory impairment	1/63 (1.6%)	1
Peripheral sensory neuropathy	3/63 (4.8%)	3
Psychiatric disorders
Anxiety	2/63 (3.2%)	4
Insomnia	1/63 (1.6%)	1
Renal and urinary disorders
Hematuria	1/63 (1.6%)	1
Proteinuria	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/63 (3.2%)	3
Dyspnea	1/63 (1.6%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/63 (1.6%)	1
Erythema multiforme	1/63 (1.6%)	1
Pruritus	2/63 (3.2%)	2
Rash maculo-papular	4/63 (6.3%)	4
Vascular disorders
Hot flashes	1/63 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Lenalidomide, Rituximab)
	Affected / at Risk (%)	# Events
Total	60/63 (95.2%)
Blood and lymphatic system disorders
Anemia	23/63 (36.5%)	79
Blood and lymphatic system disorders - Other	3/63 (4.8%)	3
Febrile neutropenia	1/63 (1.6%)	3
Cardiac disorders
Atrial fibrillation	1/63 (1.6%)	2
Chest pain - cardiac	2/63 (3.2%)	5
Palpitations	1/63 (1.6%)	2
Sinus bradycardia	3/63 (4.8%)	10
Sinus tachycardia	1/63 (1.6%)	4
Ear and labyrinth disorders
Ear pain	1/63 (1.6%)	3
Vertigo	1/63 (1.6%)	1
Endocrine disorders
Hyperthyroidism	1/63 (1.6%)	1
Hypothyroidism	4/63 (6.3%)	6
Eye disorders
Blurred vision	2/63 (3.2%)	2
Conjunctivitis	1/63 (1.6%)	1
Gastrointestinal disorders
Abdominal pain	7/63 (11.1%)	21
Bloating	3/63 (4.8%)	3
Constipation	18/63 (28.6%)	46
Diarrhea	20/63 (31.7%)	41
Dry mouth	2/63 (3.2%)	2
Dyspepsia	9/63 (14.3%)	24
Dysphagia	1/63 (1.6%)	1
Gastroesophageal reflux disease	6/63 (9.5%)	8
Gastrointestinal disorders - Other	1/63 (1.6%)	4
Ileal perforation	1/63 (1.6%)	1
Lip pain	1/63 (1.6%)	1
Mucositis oral	6/63 (9.5%)	10
Nausea	16/63 (25.4%)	39
Oral hemorrhage	1/63 (1.6%)	1
Stomach pain	3/63 (4.8%)	3
Vomiting	4/63 (6.3%)	5
General disorders
Chills	5/63 (7.9%)	14
Edema limbs	11/63 (17.5%)	40
Facial pain	1/63 (1.6%)	1
Fatigue	52/63 (82.5%)	258
Fever	5/63 (7.9%)	6
Flu like symptoms	1/63 (1.6%)	1
General disorders and administration site conditions - Other	1/63 (1.6%)	1
Infusion related reaction	20/63 (31.7%)	25
Localized edema	1/63 (1.6%)	4
Non-cardiac chest pain	4/63 (6.3%)	8
Pain	9/63 (14.3%)	19
Immune system disorders
Allergic reaction	5/63 (7.9%)	11
Cytokine release syndrome	2/63 (3.2%)	2
Infections and infestations
Appendicitis	1/63 (1.6%)	1
Gum infection	1/63 (1.6%)	1
Infections and infestations - Other	2/63 (3.2%)	2
Lung infection	1/63 (1.6%)	1
Rash pustular	1/63 (1.6%)	2
Sinusitis	4/63 (6.3%)	6
Skin infection	4/63 (6.3%)	6
Tooth infection	2/63 (3.2%)	2
Upper respiratory infection	9/63 (14.3%)	14
Urinary tract infection	2/63 (3.2%)	3
Vaginal infection	1/63 (1.6%)	1
Injury, poisoning and procedural complications
Bruising	2/63 (3.2%)	6
Investigations
Alanine aminotransferase increased	26/63 (41.3%)	85
Alkaline phosphatase increased	11/63 (17.5%)	32
Aspartate aminotransferase increased	19/63 (30.2%)	49
Blood bilirubin increased	10/63 (15.9%)	21
CD4 lymphocytes decreased	1/63 (1.6%)	1
Cholesterol high	2/63 (3.2%)	2
Creatinine increased	3/63 (4.8%)	9
Hemoglobin increased	1/63 (1.6%)	2
Lymphocyte count decreased	37/63 (58.7%)	150
Neutrophil count decreased	32/63 (50.8%)	134
Platelet count decreased	26/63 (41.3%)	103
Weight gain	2/63 (3.2%)	9
Weight loss	4/63 (6.3%)	16
White blood cell decreased	26/63 (41.3%)	141
Metabolism and nutrition disorders
Acidosis	1/63 (1.6%)	1
Anorexia	6/63 (9.5%)	8
Hyperglycemia	21/63 (33.3%)	67
Hyperkalemia	3/63 (4.8%)	3
Hypernatremia	2/63 (3.2%)	2
Hyperuricemia	3/63 (4.8%)	4
Hypoalbuminemia	7/63 (11.1%)	17
Hypocalcemia	10/63 (15.9%)	24
Hypoglycemia	8/63 (12.7%)	20
Hypokalemia	4/63 (6.3%)	12
Hyponatremia	4/63 (6.3%)	13
Hypophosphatemia	5/63 (7.9%)	21
Obesity	3/63 (4.8%)	23
Musculoskeletal and connective tissue disorders
Arthralgia	12/63 (19%)	28
Back pain	8/63 (12.7%)	22
Bone pain	2/63 (3.2%)	2
Chest wall pain	2/63 (3.2%)	3
Flank pain	2/63 (3.2%)	3
Generalized muscle weakness	3/63 (4.8%)	4
Joint range of motion decreased	1/63 (1.6%)	2
Muscle weakness lower limb	1/63 (1.6%)	4
Musculoskeletal and connective tissue disorder - Other	2/63 (3.2%)	13
Myalgia	9/63 (14.3%)	19
Neck pain	8/63 (12.7%)	16
Pain in extremity	7/63 (11.1%)	15
Nervous system disorders
Dizziness	6/63 (9.5%)	6
Dysgeusia	5/63 (7.9%)	5
Extrapyramidal disorder	1/63 (1.6%)	1
Headache	12/63 (19%)	26
Intracranial hemorrhage	1/63 (1.6%)	1
Memory impairment	1/63 (1.6%)	1
Paresthesia	3/63 (4.8%)	4
Peripheral motor neuropathy	1/63 (1.6%)	2
Peripheral sensory neuropathy	7/63 (11.1%)	22
Sinus pain	1/63 (1.6%)	1
Tremor	3/63 (4.8%)	8
Psychiatric disorders
Agitation	1/63 (1.6%)	1
Anxiety	9/63 (14.3%)	25
Depression	6/63 (9.5%)	20
Insomnia	11/63 (17.5%)	29
Libido decreased	1/63 (1.6%)	1
Restlessness	1/63 (1.6%)	1
Renal and urinary disorders
Acute kidney injury	1/63 (1.6%)	2
Renal and urinary disorders - Other	1/63 (1.6%)	2
Urinary frequency	2/63 (3.2%)	3
Urinary retention	1/63 (1.6%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/63 (1.6%)	1
Pelvic pain	1/63 (1.6%)	1
Penile pain	1/63 (1.6%)	1
Reproductive system and breast disorders - Other	1/63 (1.6%)	2
Vaginal hemorrhage	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/63 (6.3%)	7
Cough	10/63 (15.9%)	27
Dyspnea	9/63 (14.3%)	23
Hoarseness	1/63 (1.6%)	2
Nasal congestion	5/63 (7.9%)	10
Pharyngolaryngeal pain	1/63 (1.6%)	1
Pleuritic pain	1/63 (1.6%)	1
Postnasal drip	1/63 (1.6%)	5
Productive cough	1/63 (1.6%)	2
Sleep apnea	1/63 (1.6%)	1
Sore throat	2/63 (3.2%)	2
Wheezing	1/63 (1.6%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/63 (1.6%)	1
Dry skin	9/63 (14.3%)	15
Hyperhidrosis	5/63 (7.9%)	19
Pruritus	11/63 (17.5%)	17
Purpura	1/63 (1.6%)	1
Rash acneiform	3/63 (4.8%)	4
Rash maculo-papular	29/63 (46%)	67
Scalp pain	1/63 (1.6%)	1
Skin and subcutaneous tissue disorders - Other	7/63 (11.1%)	9
Skin ulceration	1/63 (1.6%)	3
Urticaria	1/63 (1.6%)	1
Vascular disorders
Flushing	2/63 (3.2%)	2
Hypertension	10/63 (15.9%)	32
Phlebitis	1/63 (1.6%)	1
Thromboembolic event	3/63 (4.8%)	4
Vasculitis	1/63 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.