Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00238238
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 97
• Locations: 79
• Arms: 3
• Duration (Months): 113
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells. This randomized phase II trial is studying how well rituximab and/or lenalidomide work in treating patients with follicular non-Hodgkin's lymphoma that is not refractory to rituximab.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab; Drug: lenalidomide	Phase 2

Detailed Description

Outline:

This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. Please see the "Arms" section for a description of each treatment arm. The primary and secondary objectives of the study are provided below.

Primary Objectives:

• To determine the response rate (overall and complete) after lenalidomide therapy and rituximab + lenalidomide in follicular NHL patients who have relapsed.

• To determine time to progression after lenalidomide therapy and rituximab and lenalidomide in follicular NHL patients who have relapsed.

Secondary Objectives:

• To compare the time to progression of the previous rituximab regimen to that obtained subsequently to lenalidomide therapy and rituximab + lenalidomide.

• To determine the toxicity profile of lenalidomide therapy and of rituximab and lenalidomide in follicular NHL patients who have received a previous rituximab regimen.

• To correlate Fc receptor polymorphism profiling with response to lenalidomide or rituximab + lenalidomide in previously treated patients with follicular NHL who have relapsed.

• To evaluate changes in Natural Killer (NK) cells, activated NK cells, activated T-cells and several plasma cytokines followed by rituximab therapy and correlation of observed changes to objective response rates.

After completion of study treatment, patients are followed for up to 10 years from study entry.

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Rituximab Versus Lenalidomide (REVLIMID™, Cc-5013) (IND#73034) Versus Rituximab + Lenalidomide in Recurrent Follicular Non-Hodgkin Lymphoma (NHL) That is Not Rituximab-Refractory
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I - rituximab Patients receive rituximab IV on days 1, 8, 15, and 22.	Biological: rituximab; Given IV
Experimental: Arm II - lenalidomide Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide; Given orally
Experimental: Arm III - lenalidomide and rituximab Patients receive lenalidomide as in arm II. Patients also receive rituximab IV on days 8, 15, 22 and 29.	Biological: rituximab; Given IV; Drug: lenalidomide; Given orally

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Duration of treatment (12 cycles)]

   Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.

2. Time to Progression [Up to 10 years]

   Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

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

• Documentation of Disease

• Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification, grade 1, 2, or 3a

• Institutional flow cytometry or immunohistochemistry must confirm Cluster of Differentiation 20 (CD20) antigen expression.

• Prior Treatment

• Patient must have been treated with rituximab either alone or in combination with chemotherapy.

• Patient must have a time to progression of ≥ 6 months from last rituximab dose.

• No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease. Maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent.

• No prior radioimmunotherapy within 12 months of study entry.

• Age ≥ 18 years.

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

• 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

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Bone marrow

• No known Central Nervous System (CNS) involvement by lymphoma.

• No known Human Immunodeficiency Virus (HIV) infection.

• Non-pregnant and non-nursing.

• Patients with a "currently active" second malignancy, other than non-melanoma skin cancers, are not eligible.

• Patients with a recent history (within 3 months of study entry) of Deep Vein Thrombosis/Pulmonary Embolism (DVT/PE) are not eligible.

• Required Initial Laboratory Values:

• Absolute Neutrophil Count (ANC) ≥ 1000/µL

• Platelet count ≥ 75,000/µL

• Creatinine < 1.5 x Upper Limit of Normal (ULN) unless attributed to lymphoma or calculated clearance > 50 mL/min (patients on dialysis are not eligible)

• Total Bilirubin ≤ 2 x ULN unless attributed to lymphoma or Gilbert's disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
2	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
3	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
4	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
5	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
6	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
7	Illinois CancerCare - Bloomington	Bloomington%	Illinois	United States	61701
8	Graham Hospital	Canton	Illinois	United States	61520
9	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
10	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
11	Memorial Hospital	Carthage	Illinois	United States	62321
12	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
13	Eureka Community Hospital	Eureka	Illinois	United States	61530
14	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
15	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
16	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
17	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
18	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
19	Mason District Hospital	Havana	Illinois	United States	62644
20	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
21	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
22	McDonough District Hospital	Macomb	Illinois	United States	61455
23	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
24	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
25	Community Cancer Center	Normal	Illinois	United States	61761
26	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
27	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
28	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
29	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
30	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
31	Proctor Hospital	Peoria	Illinois	United States	61614
32	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
33	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
34	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
35	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
36	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
37	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
38	Perry Memorial Hospital	Princeton	Illinois	United States	61356
39	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
40	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
41	Menorah Medical Center	Overland Park	Kansas	United States	66209
42	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
43	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
44	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
45	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
46	North Kansas City Hospital	Kansas City	Missouri	United States	64116
47	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
48	CCOP - Kansas City	Kansas City	Missouri	United States	64131
49	Research Medical Center	Kansas City	Missouri	United States	64132
50	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
51	Liberty Hospital	Liberty	Missouri	United States	64068
52	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
53	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
54	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
55	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
56	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
57	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
58	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
59	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
60	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
61	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
62	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
63	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
64	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
65	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
66	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
67	Cancer Centers of the Carolinas - Easley	Easley	South Carolina	United States	29640
68	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
69	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
70	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina	United States	29605
71	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
72	CCOP - Greenville	Greenville	South Carolina	United States	29615
73	Self Regional Cancer Center at Self Regional Medical Center	Greenwood	South Carolina	United States	29646
74	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina	United States	29650
75	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
76	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
77	Mountainview Medical	Berlin	Vermont	United States	05602
78	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
79	Danville Regional Medical Center	Danville	Virginia	United States	24541

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: John P. Leonard, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00238238
• Other Study ID Numbers: CALGB-50401; CALGB-50401; U10CA031946; CDR0000442872
• First Posted: Oct 13, 2005
• Last Update Posted: Mar 15, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Rituximab; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Between October 2006 and April 2011, 97 participants were accrued to the study.
Pre-assignment Detail	Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Arm/Group Title	Arm I - Rituximab	Arm II - Lenalidomide	Arm III - Lenalidomide and Rituximab
Arm/Group Description	Patients receive rituximab 375 mg/m^2 IV on days 1, 8, 15, and 22.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m^2 IV on days 8, 15, 22 and 29.
Period Title: Overall Study
STARTED	3	48	46
COMPLETED	3	45	46
NOT COMPLETED	0	3	0

Baseline Characteristics

Arm/Group Title	Arm I - Rituximab	Arm II - Lenalidomide	Arm III - Lenalidomide and Rituximab	Total
Arm/Group Description	Patients receive rituximab 375 mg/m^2 IV on days 1, 8, 15, and 22.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m^2 IV on days 8, 15, 22 and 29.	Total of all reporting groups
Overall Participants	0	45	46	91
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	64	63
Sex: Female, Male (Count of Participants)
Female	18 Infinity	19 42.2%	37 80.4%
Male	27 Infinity	27 60%	54 117.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%	0 0%
Asian	0 NaN	1 2.2%	1 2.2%
Native Hawaiian or Other Pacific Islander	1 Infinity	0 0%	1 2.2%
Black or African American	3 Infinity	1 2.2%	4 8.7%
White	37 Infinity	44 97.8%	81 176.1%
More than one race	0 NaN	0 0%	0 0%
Unknown or Not Reported	4 Infinity	0 0%	4 8.7%
Region of Enrollment (participants) [Number]
United States	45 Infinity	46 102.2%	91 197.8%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.
Time Frame	Duration of treatment (12 cycles)

Outcome Measure Data

Analysis Population Description

Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Arm/Group Title	Arm I - Rituximab	Arm II - Lenalidomide	Arm III - Lenalidomide and Rituximab
Arm/Group Description	Patients receive rituximab 375 mg/m^2 IV on days 1, 8, 15, and 22.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m^2 IV on days 8, 15, 22 and 29.
Measure Participants	0	45	46
Number (95% Confidence Interval) [percentage of participants]	53.3 Infinity	76.1 169.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II - Lenalidomide, Arm III - Lenalidomide and Rituximab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Time to Progression
Description	Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Arm/Group Title	Arm I - Rituximab	Arm II - Lenalidomide	Arm III - Lenalidomide and Rituximab
Arm/Group Description	Patients receive rituximab 375 mg/m^2 IV on days 1, 8, 15, and 22.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m^2 IV on days 8, 15, 22 and 29.
Measure Participants	0	45	46
Median (95% Confidence Interval) [years]	1.1	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II - Lenalidomide, Arm III - Lenalidomide and Rituximab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log Rank
	Comments

Adverse Events

Adverse Event Reporting Description	90 participants, on Arms II and III, were evaluable for adverse events.
Arm/Group Title	Arm I - Rituximab		Arm II - Lenalidomide		Arm III - Lenalidomide and Rituximab
Arm/Group Description	Patients receive rituximab 375 mg/m^2 IV on days 1, 8, 15, and 22.		Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.		Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m^2 IV on days 8, 15, 22 and 29.
All Cause Mortality
	Arm I - Rituximab		Arm II - Lenalidomide		Arm III - Lenalidomide and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I - Rituximab		Arm II - Lenalidomide		Arm III - Lenalidomide and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		8/45 (17.8%)		12/45 (26.7%)
Blood and lymphatic system disorders
Febrile neutropenia	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Hemoglobin decreased	0/0 (NaN)	0	4/45 (8.9%)	4	4/45 (8.9%)	4
Cardiac disorders
Sinus arrhythmia	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Sinus tachycardia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Endocrine disorders
Hypothyroidism	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Eye disorders
Dry eye syndrome	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	4
Vision blurred	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Gastrointestinal disorders
Abdominal distension	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Abdominal pain	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Colitis	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Constipation	0/0 (NaN)	0	1/45 (2.2%)	2	4/45 (8.9%)	8
Diarrhea	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Dyspepsia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Dysphagia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Ear, nose and throat examination abnormal	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Esophageal pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Hemorrhoids	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Nausea	0/0 (NaN)	0	2/45 (4.4%)	2	3/45 (6.7%)	3
Obstruction gastric	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Oral pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Vomiting	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	2
General disorders
Chest pain	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Chills	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Death NOS	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Disease progression	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Edema limbs	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	2
Fatigue	0/0 (NaN)	0	5/45 (11.1%)	6	7/45 (15.6%)	11
Fever	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Gait abnormal	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Pain	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Immune system disorders
Cytokine release syndrome	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Infections and infestations
Bronchitis	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Infection	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Opportunistic infection	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Pneumonia	0/0 (NaN)	0	2/45 (4.4%)	2	2/45 (4.4%)	2
Sepsis	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Skin infection	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Vaginal infection	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Injury, poisoning and procedural complications
Intraoperative musculoskeletal injury	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Investigations
Alanine aminotransferase increased	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Alkaline phosphatase increased	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Aspartate aminotransferase increased	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	3
Blood bilirubin increased	0/0 (NaN)	0	1/45 (2.2%)	1	3/45 (6.7%)	4
Creatinine increased	0/0 (NaN)	0	1/45 (2.2%)	1	3/45 (6.7%)	4
Electrocardiogram QTc interval prolonged	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
INR increased	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Leukocyte count decreased	0/0 (NaN)	0	4/45 (8.9%)	4	5/45 (11.1%)	6
Lymphocyte count decreased	0/0 (NaN)	0	2/45 (4.4%)	2	3/45 (6.7%)	3
Neutrophil count decreased	0/0 (NaN)	0	2/45 (4.4%)	2	4/45 (8.9%)	6
Platelet count decreased	0/0 (NaN)	0	6/45 (13.3%)	7	5/45 (11.1%)	6
Weight loss	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Metabolism and nutrition disorders
Alkalosis	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Anorexia	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Blood glucose increased	0/0 (NaN)	0	4/45 (8.9%)	4	6/45 (13.3%)	7
Dehydration	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Serum albumin decreased	0/0 (NaN)	0	0/45 (0%)	0	5/45 (11.1%)	5
Serum calcium decreased	0/0 (NaN)	0	2/45 (4.4%)	2	4/45 (8.9%)	4
Serum glucose decreased	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Serum magnesium increased	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Serum phosphate decreased	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Serum potassium decreased	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Serum sodium decreased	0/0 (NaN)	0	1/45 (2.2%)	1	5/45 (11.1%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Back pain	0/0 (NaN)	0	2/45 (4.4%)	2	1/45 (2.2%)	1
Bone pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Muscle weakness lower limb	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Myalgia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Neck pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Pain in extremity	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Nervous system disorders
Dysgeusia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Ischemia cerebrovascular	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Mini mental status examination abnormal	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Neuralgia	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Peripheral sensory neuropathy	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Seizure	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Speech disorder	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Psychiatric disorders
Depression	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Insomnia	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Renal and urinary disorders
Kidney pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Proteinuria	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Renal failure	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Ureteric obstruction	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Allergic rhinitis	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Bronchospasm	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Cough	0/0 (NaN)	0	2/45 (4.4%)	3	4/45 (8.9%)	4
Dyspnea	0/0 (NaN)	0	3/45 (6.7%)	5	4/45 (8.9%)	4
Hypoxia	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Pleural effusion	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Skin and subcutaneous tissue disorders
Dry skin	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	5
Erythema multiforme	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Pruritus	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Sweating	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Vascular disorders
Flushing	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Hot flashes	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Hypotension	0/0 (NaN)	0	2/45 (4.4%)	2	1/45 (2.2%)	1
Thrombosis	0/0 (NaN)	0	3/45 (6.7%)	3	2/45 (4.4%)	2
Other (Not Including Serious) Adverse Events
	Arm I - Rituximab		Arm II - Lenalidomide		Arm III - Lenalidomide and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		44/45 (97.8%)		41/45 (91.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Hemoglobin decreased	0/0 (NaN)	0	19/45 (42.2%)	89	17/45 (37.8%)	86
Lymph node pain	0/0 (NaN)	0	1/45 (2.2%)	2	0/45 (0%)	0
Cardiac disorders
Cardiac disorder	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Cardiac pain	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Left ventricular dysfunction	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Sinus bradycardia	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	3
Ventricular arrhythmia	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Ear and labyrinth disorders
Ear pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
External ear pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Hearing impaired	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Endocrine disorders
Hypothyroidism	0/0 (NaN)	0	1/45 (2.2%)	1	6/45 (13.3%)	24
Eye disorders
Dry eye syndrome	0/0 (NaN)	0	3/45 (6.7%)	5	2/45 (4.4%)	3
Eye disorder	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Glaucoma	0/0 (NaN)	0	1/45 (2.2%)	3	0/45 (0%)	0
Watering eyes	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	3
Gastrointestinal disorders
Abdominal distension	0/0 (NaN)	0	2/45 (4.4%)	2	2/45 (4.4%)	7
Abdominal pain	0/0 (NaN)	0	3/45 (6.7%)	6	4/45 (8.9%)	9
Anal hemorrhage	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Constipation	0/0 (NaN)	0	21/45 (46.7%)	40	16/45 (35.6%)	45
Diarrhea	0/0 (NaN)	0	14/45 (31.1%)	46	14/45 (31.1%)	34
Dry mouth	0/0 (NaN)	0	3/45 (6.7%)	12	4/45 (8.9%)	6
Dyspepsia	0/0 (NaN)	0	6/45 (13.3%)	7	2/45 (4.4%)	4
Ear, nose and throat examination abnormal	0/0 (NaN)	0	2/45 (4.4%)	2	1/45 (2.2%)	3
Esophageal pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Esophagitis	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Gastrointestinal disorder	0/0 (NaN)	0	2/45 (4.4%)	4	0/45 (0%)	0
Gastroscopy abnormal	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Hemorrhoids	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Nausea	0/0 (NaN)	0	16/45 (35.6%)	40	12/45 (26.7%)	32
Oral pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Rectal hemorrhage	0/0 (NaN)	0	1/45 (2.2%)	2	0/45 (0%)	0
Stomach pain	0/0 (NaN)	0	1/45 (2.2%)	3	0/45 (0%)	0
Toothache	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	3
Vomiting	0/0 (NaN)	0	4/45 (8.9%)	9	6/45 (13.3%)	7
General disorders
Chest pain	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	7
Chills	0/0 (NaN)	0	2/45 (4.4%)	2	7/45 (15.6%)	7
Edema limbs	0/0 (NaN)	0	9/45 (20%)	28	6/45 (13.3%)	11
Fatigue	0/0 (NaN)	0	35/45 (77.8%)	138	33/45 (73.3%)	166
Fever	0/0 (NaN)	0	2/45 (4.4%)	2	7/45 (15.6%)	7
Flu-like symptoms	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
General symptom	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Localized edema	0/0 (NaN)	0	2/45 (4.4%)	3	0/45 (0%)	0
Pain	0/0 (NaN)	0	4/45 (8.9%)	5	4/45 (8.9%)	16
Hepatobiliary disorders
Gallbladder pain	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Immune system disorders
Cytokine release syndrome	0/0 (NaN)	0	1/45 (2.2%)	1	12/45 (26.7%)	12
Hypersensitivity	0/0 (NaN)	0	3/45 (6.7%)	4	3/45 (6.7%)	3
Immune system disorder	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Infections and infestations
Bronchitis	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Catheter related infection	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Gastric infection	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Gingival infection	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	3
Infection	0/0 (NaN)	0	2/45 (4.4%)	2	2/45 (4.4%)	2
Otitis media	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Pharyngitis	0/0 (NaN)	0	0/45 (0%)	0	2/45 (4.4%)	2
Rhinitis infective	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Sinusitis	0/0 (NaN)	0	3/45 (6.7%)	3	8/45 (17.8%)	15
Skin infection	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Tooth infection	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Tracheitis	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Upper respiratory infection	0/0 (NaN)	0	5/45 (11.1%)	7	2/45 (4.4%)	3
Urinary tract infection	0/0 (NaN)	0	0/45 (0%)	0	3/45 (6.7%)	11
Vaginal infection	0/0 (NaN)	0	1/45 (2.2%)	2	1/45 (2.2%)	2
Injury, poisoning and procedural complications
Bruising	0/0 (NaN)	0	1/45 (2.2%)	5	1/45 (2.2%)	1
Thermal burn	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Vascular access complication	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Investigations
Alanine aminotransferase increased	0/0 (NaN)	0	8/45 (17.8%)	27	9/45 (20%)	35
Alkaline phosphatase increased	0/0 (NaN)	0	5/45 (11.1%)	14	2/45 (4.4%)	4
Aspartate aminotransferase increased	0/0 (NaN)	0	8/45 (17.8%)	21	10/45 (22.2%)	33
Blood bilirubin increased	0/0 (NaN)	0	2/45 (4.4%)	6	8/45 (17.8%)	31
Creatinine increased	0/0 (NaN)	0	6/45 (13.3%)	10	4/45 (8.9%)	14
INR increased	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Laboratory test abnormal	0/0 (NaN)	0	1/45 (2.2%)	3	2/45 (4.4%)	15
Leukocyte count decreased	0/0 (NaN)	0	21/45 (46.7%)	86	16/45 (35.6%)	131
Lymphocyte count decreased	0/0 (NaN)	0	9/45 (20%)	21	13/45 (28.9%)	80
Neutrophil count decreased	0/0 (NaN)	0	19/45 (42.2%)	94	25/45 (55.6%)	123
Platelet count decreased	0/0 (NaN)	0	25/45 (55.6%)	96	23/45 (51.1%)	114
Serum cholesterol increased	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Weight gain	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Weight loss	0/0 (NaN)	0	2/45 (4.4%)	2	3/45 (6.7%)	4
Metabolism and nutrition disorders
Anorexia	0/0 (NaN)	0	6/45 (13.3%)	12	5/45 (11.1%)	8
Blood glucose increased	0/0 (NaN)	0	15/45 (33.3%)	50	14/45 (31.1%)	55
Blood uric acid increased	0/0 (NaN)	0	3/45 (6.7%)	5	2/45 (4.4%)	2
Glucose intolerance	0/0 (NaN)	0	1/45 (2.2%)	4	0/45 (0%)	0
Serum albumin decreased	0/0 (NaN)	0	7/45 (15.6%)	12	6/45 (13.3%)	18
Serum calcium decreased	0/0 (NaN)	0	8/45 (17.8%)	24	10/45 (22.2%)	38
Serum calcium increased	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	11
Serum glucose decreased	0/0 (NaN)	0	4/45 (8.9%)	6	7/45 (15.6%)	14
Serum magnesium decreased	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Serum phosphate decreased	0/0 (NaN)	0	6/45 (13.3%)	10	6/45 (13.3%)	23
Serum potassium decreased	0/0 (NaN)	0	7/45 (15.6%)	13	6/45 (13.3%)	27
Serum potassium increased	0/0 (NaN)	0	2/45 (4.4%)	3	2/45 (4.4%)	4
Serum sodium decreased	0/0 (NaN)	0	6/45 (13.3%)	20	6/45 (13.3%)	16
Serum sodium increased	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Serum triglycerides increased	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/0 (NaN)	0	1/45 (2.2%)	1	7/45 (15.6%)	13
Arthritis	0/0 (NaN)	0	0/45 (0%)	0	3/45 (6.7%)	8
Back pain	0/0 (NaN)	0	6/45 (13.3%)	9	6/45 (13.3%)	14
Bone pain	0/0 (NaN)	0	1/45 (2.2%)	5	3/45 (6.7%)	4
Chest wall pain	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Muscle weakness	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Muscle weakness upper limb	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Musculoskeletal disorder	0/0 (NaN)	0	3/45 (6.7%)	5	4/45 (8.9%)	15
Myalgia	0/0 (NaN)	0	7/45 (15.6%)	16	6/45 (13.3%)	20
Myositis	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Neck pain	0/0 (NaN)	0	3/45 (6.7%)	3	0/45 (0%)	0
Pain in extremity	0/0 (NaN)	0	4/45 (8.9%)	6	4/45 (8.9%)	9
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	2
Tumor pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Nervous system disorders
Ataxia	0/0 (NaN)	0	1/45 (2.2%)	4	0/45 (0%)	0
Depressed level of consciousness	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Dizziness	0/0 (NaN)	0	8/45 (17.8%)	11	10/45 (22.2%)	16
Dysgeusia	0/0 (NaN)	0	5/45 (11.1%)	18	3/45 (6.7%)	7
Headache	0/0 (NaN)	0	5/45 (11.1%)	16	5/45 (11.1%)	10
Memory impairment	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Neuralgia	0/0 (NaN)	0	1/45 (2.2%)	3	0/45 (0%)	0
Neurological disorder NOS	0/0 (NaN)	0	1/45 (2.2%)	2	1/45 (2.2%)	1
Olfactory nerve disorder	0/0 (NaN)	0	1/45 (2.2%)	4	0/45 (0%)	0
Peripheral motor neuropathy	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	2
Peripheral sensory neuropathy	0/0 (NaN)	0	15/45 (33.3%)	32	17/45 (37.8%)	51
Syncope	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Tremor	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	4
Trigeminal nerve disorder	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Psychiatric disorders
Anxiety	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	2
Depression	0/0 (NaN)	0	4/45 (8.9%)	15	1/45 (2.2%)	2
Insomnia	0/0 (NaN)	0	4/45 (8.9%)	6	4/45 (8.9%)	10
Libido decreased	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Renal and urinary disorders
Bladder spasm	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Proteinuria	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	1
Urinary frequency	0/0 (NaN)	0	2/45 (4.4%)	2	3/45 (6.7%)	4
Urinary incontinence	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Urinary retention	0/0 (NaN)	0	1/45 (2.2%)	1	2/45 (4.4%)	7
Reproductive system and breast disorders
Pelvic pain	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	5
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/0 (NaN)	0	9/45 (20%)	20	6/45 (13.3%)	12
Bronchospasm	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Cough	0/0 (NaN)	0	8/45 (17.8%)	15	11/45 (24.4%)	30
Dyspnea	0/0 (NaN)	0	6/45 (13.3%)	13	8/45 (17.8%)	14
Nasal congestion	0/0 (NaN)	0	1/45 (2.2%)	2	1/45 (2.2%)	1
Pharyngolaryngeal pain	0/0 (NaN)	0	2/45 (4.4%)	3	4/45 (8.9%)	6
Pleural effusion	0/0 (NaN)	0	1/45 (2.2%)	2	0/45 (0%)	0
Pneumonitis	0/0 (NaN)	0	0/45 (0%)	0	1/45 (2.2%)	7
Pulmonary hemorrhage	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Respiratory disorder	0/0 (NaN)	0	4/45 (8.9%)	4	6/45 (13.3%)	8
Skin and subcutaneous tissue disorders
Alopecia	0/0 (NaN)	0	1/45 (2.2%)	3	0/45 (0%)	0
Dry skin	0/0 (NaN)	0	7/45 (15.6%)	12	2/45 (4.4%)	2
Erythema multiforme	0/0 (NaN)	0	10/45 (22.2%)	15	8/45 (17.8%)	22
Petechiae	0/0 (NaN)	0	2/45 (4.4%)	2	0/45 (0%)	0
Pruritus	0/0 (NaN)	0	9/45 (20%)	17	6/45 (13.3%)	16
Rash acneiform	0/0 (NaN)	0	1/45 (2.2%)	1	1/45 (2.2%)	1
Rash desquamating	0/0 (NaN)	0	11/45 (24.4%)	16	10/45 (22.2%)	13
Skin disorder	0/0 (NaN)	0	6/45 (13.3%)	9	8/45 (17.8%)	11
Skin hypopigmentation	0/0 (NaN)	0	1/45 (2.2%)	5	0/45 (0%)	0
Skin ulceration	0/0 (NaN)	0	1/45 (2.2%)	1	0/45 (0%)	0
Sweating	0/0 (NaN)	0	6/45 (13.3%)	8	3/45 (6.7%)	4
Vascular disorders
Hot flashes	0/0 (NaN)	0	1/45 (2.2%)	8	0/45 (0%)	0
Hypotension	0/0 (NaN)	0	3/45 (6.7%)	5	0/45 (0%)	0
Peripheral ischemia	0/0 (NaN)	0	1/45 (2.2%)	2	0/45 (0%)	0
Thrombosis	0/0 (NaN)	0	4/45 (8.9%)	7	1/45 (2.2%)	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.