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Trial record 97 of 179 for:    LENALIDOMIDE AND Leukemia

Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00602459
Recruitment Status : Completed
First Posted : January 28, 2008
Results First Posted : April 4, 2017
Last Update Posted : November 29, 2018
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Stage I Chronic Lymphocytic Leukemia
Stage II Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage IV Chronic Lymphocytic Leukemia
Interventions Drug: Cyclophosphamide
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Biological: Rituximab
Enrollment 418
Recruitment Details From January 2008 to August 2012, 418 participants were recruited to this study.
Pre-assignment Details  
Arm/Group Title Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Hide Arm/Group Description Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3. Patients receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.
Period Title: Initial Registration/Randomization
Started 138 140 140 0
Completed 133 130 137 0
Not Completed 5 10 3 0
Period Title: Re-assignment After Del(11q22.3) Testing
Started 123 109 137 31
Completed 123 109 137 31
Not Completed 0 0 0 0
Arm/Group Title Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide) Total
Hide Arm/Group Description Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3. Patients receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle. Total of all reporting groups
Overall Number of Baseline Participants 123 109 137 31 400
Hide Baseline Analysis Population Description
400 participants were evaluable for analysis. (18 participants were excluded from the analysis.)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 109 participants 137 participants 31 participants 400 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
80
  65.0%
67
  61.5%
88
  64.2%
21
  67.7%
256
  64.0%
>=65 years
43
  35.0%
42
  38.5%
49
  35.8%
10
  32.3%
144
  36.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 109 participants 137 participants 31 participants 400 participants
Female
40
  32.5%
40
  36.7%
51
  37.2%
8
  25.8%
139
  34.8%
Male
83
  67.5%
69
  63.3%
86
  62.8%
23
  74.2%
261
  65.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 123 participants 109 participants 137 participants 31 participants 400 participants
Canada 15 14 16 8 53
United States 108 95 121 23 347
1.Primary Outcome
Title 2-Year Progression Free Survival (PFS) Rate
Hide Description Proportion of participants who were alive and progression free at 2 years.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients re-assigned to Arm C were split into two analysis groups, patients with del(11q22.3), as assessed by interphase cytogenetics and present in at least 20% of cells, and those without del(11q22.3). This endpoint is limited to patients without del(11q22.3).
Arm/Group Title Arm A, FR in Non-del(11q22.3) Arm B, FR+L in Non-del(11q22.3) Arm C1, FCR in Non-del(11q22.3)
Hide Arm/Group Description:
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate (F) 25 mg/m^2/day IV over 30 minutes or PO on days 1-5.
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate (F) 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide (L) 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle.
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (F) (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (C) (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Overall Number of Participants Analyzed 123 109 110
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.64
(0.57 to 0.71)
0.71
(0.63 to 0.78)
0.74
(0.66 to 0.80)
2.Secondary Outcome
Title Overall Response Rate in Patients Without Del(11q22.3)
Hide Description Percentage of non-del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions.
Time Frame Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients without Del(11q22.3) were included in this analysis.
Arm/Group Title Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide)
Hide Arm/Group Description:
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5.
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle.
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Overall Number of Participants Analyzed 123 109 110
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
75
(68 to 81)
69
(61 to 76)
71
(63 to 78)
3.Secondary Outcome
Title Overall Response Rates in Patients With Del(11q22.3)
Hide Description Percentage of del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions.
Time Frame Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with del(11q22.3) were included in this analysis.
Arm/Group Title Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Hide Arm/Group Description:
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Patients receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 27 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
59
(42 to 75)
74
(58 to 86)
4.Secondary Outcome
Title PFS Rate of Patients With Del(11q22.3)
Hide Description Proportion of del (11q22.3) participants who were alive and progression free at 2 years.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint is limited to patients with del(11q22.3).
Arm/Group Title Arm C2, FCR in Del(11q22.3) Arm D, FCR+L in Del(11q22.3)
Hide Arm/Group Description:
Participants who have del(11q22.3) receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Patients who have del(11q22.3)receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 27 31
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.56
(0.38 to 0.72)
0.65
(0.48 to 0.79)
5.Secondary Outcome
Title Time-to-progression in Patients Without Del(11q22.3)
Hide Description Time to progression (TTP) was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progressive disease (PD) required at least one of the following: >= 50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes, >= 50% increase in the product of at least two lymphnodes, >= 50% increase in the enlargement of the liver and/or spleen.
Time Frame Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint is limited to patients without del(11q22.3).
Arm/Group Title Arm A, FR in Non-del(11q22.3) Arm B, FR+L in Non-del(11q22.3) Arm C1, FCR in Non-del(11q22.3)
Hide Arm/Group Description:
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate (F) 25 mg/m^2/day IV over 30 minutes or PO on days 1-5.
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate (F) 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide (L) 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle.
Participants, who are non-del(11q22.3), receive induction therapy (every 28 days for up to 6 cycles) of: rituximab (R) IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (F) (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (C) (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Overall Number of Participants Analyzed 123 109 110
Median (95% Confidence Interval)
Unit of Measure: months
43.5
(32.8 to 49.9)
66.0 [1] 
(44.5 to NA)
78.0 [1] 
(57.9 to NA)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment
6.Secondary Outcome
Title Time-to-progression in Patients With Del(11q22.3)
Hide Description Time to progression (TTP) in del(11q22.3) participants was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method.
Time Frame Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint is limited to patients with del(11q22.3).
Arm/Group Title Arm C2, FCR in Del(11q22.3) Arm D, FCR+L in Del(11q22.3)
Hide Arm/Group Description:
Participants who have del(11q22.3) receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Patients who have del(11q22.3)receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.
Overall Number of Participants Analyzed 27 31
Median (95% Confidence Interval)
Unit of Measure: months
35.5
(21.8 to 65.5)
44.6
(25.7 to 50.7)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Hide Arm/Group Description Participants receive induction therapy (every 28 days for up to 6 cycles) of: Patients receive rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle. Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3. Patients receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.
All-Cause Mortality
Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/123 (10.57%)      21/109 (19.27%)      14/137 (10.22%)      3/31 (9.68%)    
Blood and lymphatic system disorders         
Febrile neutropenia  1  1/123 (0.81%)  1 6/109 (5.50%)  6 4/137 (2.92%)  4 0/31 (0.00%)  0
Hemoglobin decreased  1  8/123 (6.50%)  8 15/109 (13.76%)  17 10/137 (7.30%)  10 1/31 (3.23%)  1
Hemolysis  1  1/123 (0.81%)  1 2/109 (1.83%)  2 0/137 (0.00%)  0 1/31 (3.23%)  1
Lymphatic disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Cardiac disorders         
Atrial fibrillation  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Cardiac disorder  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Left ventricular dysfunction  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Left ventricular failure  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Premature ventricular contractions  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Sinus tachycardia  1  1/123 (0.81%)  1 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Ear and labyrinth disorders         
Ear disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Ear pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Tinnitus  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Gastrointestinal disorders         
Abdominal distension  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Abdominal pain  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anal fistula  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Ascites  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Colitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Constipation  1  0/123 (0.00%)  0 3/109 (2.75%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
Diarrhea  1  0/123 (0.00%)  0 3/109 (2.75%)  3 1/137 (0.73%)  1 1/31 (3.23%)  1
Dry mouth  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Dyspepsia  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Gastric perforation  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Lower gastrointestinal hemorrhage  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Mucositis oral  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Nausea  1  2/123 (1.63%)  2 8/109 (7.34%)  8 2/137 (1.46%)  2 0/31 (0.00%)  0
Oral pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Periodontal disease  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Upper gastrointestinal hemorrhage  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Vomiting  1  2/123 (1.63%)  2 3/109 (2.75%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
General disorders         
Chest pain  1  1/123 (0.81%)  1 3/109 (2.75%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Chills  1  1/123 (0.81%)  1 7/109 (6.42%)  7 2/137 (1.46%)  2 0/31 (0.00%)  0
Death NOS  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Disease progression  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Edema limbs  1  1/123 (0.81%)  1 3/109 (2.75%)  4 1/137 (0.73%)  1 0/31 (0.00%)  0
Fatigue  1  8/123 (6.50%)  8 15/109 (13.76%)  17 6/137 (4.38%)  6 1/31 (3.23%)  1
Fever  1  0/123 (0.00%)  0 5/109 (4.59%)  5 2/137 (1.46%)  2 0/31 (0.00%)  0
Localized edema  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Pain  1  2/123 (1.63%)  2 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Immune system disorders         
Hypersensitivity  1  0/123 (0.00%)  0 4/109 (3.67%)  4 1/137 (0.73%)  1 0/31 (0.00%)  0
Infections and infestations         
Bladder infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Bronchitis  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Joint infection  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Peripheral nerve infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pneumonia  1  0/123 (0.00%)  0 2/109 (1.83%)  2 3/137 (2.19%)  3 0/31 (0.00%)  0
Sepsis  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Sinusitis  1  0/123 (0.00%)  0 3/109 (2.75%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Skin infection  1  0/123 (0.00%)  0 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Upper respiratory infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Urinary tract infection  1  0/123 (0.00%)  0 1/109 (0.92%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Vaginal infection  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Vulvitis  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Investigations         
Activated partial thromboplastin time prolonged  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Alanine aminotransferase increased  1  0/123 (0.00%)  0 3/109 (2.75%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Alkaline phosphatase increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 3/137 (2.19%)  3 0/31 (0.00%)  0
Aspartate aminotransferase increased  1  0/123 (0.00%)  0 5/109 (4.59%)  5 1/137 (0.73%)  1 0/31 (0.00%)  0
Blood bilirubin increased  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 1/31 (3.23%)  1
Carbon monoxide diffusing capacity decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Creatine phosphokinase increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Creatinine increased  1  0/123 (0.00%)  0 5/109 (4.59%)  5 2/137 (1.46%)  2 0/31 (0.00%)  0
Electrocardiogram QTc interval prolonged  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Haptoglobin decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
INR increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Laboratory test abnormal  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Leukocyte count decreased  1  1/123 (0.81%)  1 7/109 (6.42%)  7 5/137 (3.65%)  5 0/31 (0.00%)  0
Lymphocyte count decreased  1  1/123 (0.81%)  1 4/109 (3.67%)  4 4/137 (2.92%)  4 0/31 (0.00%)  0
Neutrophil count decreased  1  7/123 (5.69%)  7 12/109 (11.01%)  14 8/137 (5.84%)  8 0/31 (0.00%)  0
Platelet count decreased  1  9/123 (7.32%)  9 10/109 (9.17%)  12 9/137 (6.57%)  9 0/31 (0.00%)  0
Serum cholesterol increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Weight loss  1  2/123 (1.63%)  2 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Metabolism and nutrition disorders         
Acidosis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Alkalosis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anorexia  1  1/123 (0.81%)  1 5/109 (4.59%)  5 1/137 (0.73%)  1 0/31 (0.00%)  0
Blood bicarbonate decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Blood glucose increased  1  2/123 (1.63%)  2 9/109 (8.26%)  9 4/137 (2.92%)  4 0/31 (0.00%)  0
Blood uric acid increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Dehydration  1  1/123 (0.81%)  1 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Renal tubular disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Serum albumin decreased  1  0/123 (0.00%)  0 2/109 (1.83%)  2 2/137 (1.46%)  2 0/31 (0.00%)  0
Serum calcium decreased  1  2/123 (1.63%)  2 5/109 (4.59%)  5 3/137 (2.19%)  3 0/31 (0.00%)  0
Serum calcium increased  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Serum glucose decreased  1  2/123 (1.63%)  2 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Serum magnesium decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Serum magnesium increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Serum phosphate decreased  1  0/123 (0.00%)  0 4/109 (3.67%)  4 0/137 (0.00%)  0 0/31 (0.00%)  0
Serum potassium decreased  1  2/123 (1.63%)  2 5/109 (4.59%)  5 2/137 (1.46%)  2 0/31 (0.00%)  0
Serum potassium increased  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Serum sodium decreased  1  1/123 (0.81%)  1 2/109 (1.83%)  2 5/137 (3.65%)  5 0/31 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/123 (0.00%)  0 2/109 (1.83%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
Back pain  1  1/123 (0.81%)  1 1/109 (0.92%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Muscle weakness  1  0/123 (0.00%)  0 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Muscle weakness left-sided  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Muscle weakness lower limb  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Muscle weakness upper limb  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Myalgia  1  0/123 (0.00%)  0 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Pain in extremity  1  1/123 (0.81%)  1 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Treatment related secondary malignancy  1  2/123 (1.63%)  2 0/109 (0.00%)  0 3/137 (2.19%)  3 0/31 (0.00%)  0
Tumor pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Nervous system disorders         
Ataxia  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Dizziness  1  1/123 (0.81%)  1 4/109 (3.67%)  4 1/137 (0.73%)  1 0/31 (0.00%)  0
Dysgeusia  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Encephalopathy  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Headache  1  1/123 (0.81%)  1 3/109 (2.75%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Memory impairment  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Peripheral motor neuropathy  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Sinus pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Speech disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Syncope  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Psychiatric disorders         
Agitation  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anxiety  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Confusion  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Depression  1  0/123 (0.00%)  0 2/109 (1.83%)  2 2/137 (1.46%)  2 1/31 (3.23%)  1
Insomnia  1  0/123 (0.00%)  0 1/109 (0.92%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Personality change  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Renal and urinary disorders         
Glomerular filtration rate decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Hemoglobin urine positive  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Renal failure  1  1/123 (0.81%)  1 3/109 (2.75%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
Urethral pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Urinary frequency  1  0/123 (0.00%)  0 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Urinary incontinence  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Urinary retention  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Urogenital disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Reproductive system and breast disorders         
Breast pain  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Allergic rhinitis  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Atelectasis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Bronchospasm  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Cough  1  2/123 (1.63%)  2 8/109 (7.34%)  9 1/137 (0.73%)  1 0/31 (0.00%)  0
Dyspnea  1  5/123 (4.07%)  5 7/109 (6.42%)  7 3/137 (2.19%)  3 0/31 (0.00%)  0
Hypoxia  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Pharyngolaryngeal pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pleural effusion  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Respiratory disorder  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Voice alteration  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Skin and subcutaneous tissue disorders         
Petechiae  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pruritus  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Rash desquamating  1  2/123 (1.63%)  2 3/109 (2.75%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Sweating  1  1/123 (0.81%)  1 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Vascular disorders         
Flushing  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Hematoma  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Hot flashes  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Hypertension  1  0/123 (0.00%)  0 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Hypotension  1  0/123 (0.00%)  0 3/109 (2.75%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Vascular disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 6
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm A (Rituximab, Fludarabine Phosphate) Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   117/123 (95.12%)      107/109 (98.17%)      132/137 (96.35%)      30/31 (96.77%)    
Blood and lymphatic system disorders         
Blood disorder  1  8/123 (6.50%)  22 5/109 (4.59%)  21 8/137 (5.84%)  26 1/31 (3.23%)  1
Febrile neutropenia  1  14/123 (11.38%)  17 13/109 (11.93%)  13 18/137 (13.14%)  18 5/31 (16.13%)  6
Hemoglobin decreased  1  92/123 (74.80%)  398 90/109 (82.57%)  436 116/137 (84.67%)  516 23/31 (74.19%)  91
Hemolysis  1  1/123 (0.81%)  1 3/109 (2.75%)  3 0/137 (0.00%)  0 2/31 (6.45%)  2
Lymph node pain  1  6/123 (4.88%)  16 0/109 (0.00%)  0 2/137 (1.46%)  4 1/31 (3.23%)  1
Lymphatic disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Thrombotic microangiopathy  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Cardiac disorders         
Arrhythmia  1  4/123 (3.25%)  4 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Atrial fibrillation  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Atrial flutter  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Cardiac disorder  1  0/123 (0.00%)  0 2/109 (1.83%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Conduction disorder  1  1/123 (0.81%)  4 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Edema  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Left ventricular dysfunction  1  1/123 (0.81%)  1 1/109 (0.92%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Left ventricular failure  1  0/123 (0.00%)  0 1/109 (0.92%)  1 3/137 (2.19%)  3 0/31 (0.00%)  0
Myocardial ischemia  1  2/123 (1.63%)  2 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Palpitations  1  1/123 (0.81%)  1 4/109 (3.67%)  4 3/137 (2.19%)  3 0/31 (0.00%)  0
Pericardial effusion  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Premature ventricular contractions  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 1/31 (3.23%)  1
Restrictive cardiomyopathy  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Sinus bradycardia  1  0/123 (0.00%)  0 4/109 (3.67%)  8 2/137 (1.46%)  6 1/31 (3.23%)  1
Sinus tachycardia  1  4/123 (3.25%)  5 9/109 (8.26%)  9 3/137 (2.19%)  4 2/31 (6.45%)  2
Ventricular bigeminy  1  1/123 (0.81%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Ear and labyrinth disorders         
Ear disorder  1  2/123 (1.63%)  3 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Ear pain  1  1/123 (0.81%)  1 4/109 (3.67%)  5 3/137 (2.19%)  8 1/31 (3.23%)  1
External ear pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Hearing impaired  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 1/31 (3.23%)  3
Middle ear inflammation  1  1/123 (0.81%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Tinnitus  1  5/123 (4.07%)  16 0/109 (0.00%)  0 1/137 (0.73%)  6 0/31 (0.00%)  0
Endocrine disorders         
Endocrine disorder  1  0/123 (0.00%)  0 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Hyperthyroidism  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Hypothyroidism  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Eye disorders         
Cataract  1  0/123 (0.00%)  0 0/109 (0.00%)  0 3/137 (2.19%)  4 0/31 (0.00%)  0
Conjunctivitis  1  1/123 (0.81%)  1 1/109 (0.92%)  1 1/137 (0.73%)  2 0/31 (0.00%)  0
Diplopia  1  0/123 (0.00%)  0 1/109 (0.92%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Dry eye syndrome  1  1/123 (0.81%)  3 0/109 (0.00%)  0 2/137 (1.46%)  4 0/31 (0.00%)  0
Eye disorder  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  4 0/31 (0.00%)  0
Eye pain  1  3/123 (2.44%)  6 1/109 (0.92%)  2 1/137 (0.73%)  4 0/31 (0.00%)  0
Eyelid function disorder  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Flashing vision  1  1/123 (0.81%)  1 2/109 (1.83%)  6 1/137 (0.73%)  2 0/31 (0.00%)  0
Keratitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Photophobia  1  0/123 (0.00%)  0 4/109 (3.67%)  5 0/137 (0.00%)  0 1/31 (3.23%)  4
Retinopathy  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Vision blurred  1  6/123 (4.88%)  7 8/109 (7.34%)  10 4/137 (2.92%)  4 0/31 (0.00%)  0
Vitreous hemorrhage  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Watering eyes  1  0/123 (0.00%)  0 1/109 (0.92%)  2 1/137 (0.73%)  1 0/31 (0.00%)  0
Gastrointestinal disorders         
Abdominal distension  1  1/123 (0.81%)  1 4/109 (3.67%)  7 2/137 (1.46%)  2 0/31 (0.00%)  0
Abdominal pain  1  17/123 (13.82%)  22 18/109 (16.51%)  26 23/137 (16.79%)  24 4/31 (12.90%)  5
Anal exam abnormal  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Anal mucositis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anal pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Ascites  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Cheilitis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Colitis  1  1/123 (0.81%)  1 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Colonic fistula  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Constipation  1  35/123 (28.46%)  90 47/109 (43.12%)  123 46/137 (33.58%)  89 10/31 (32.26%)  23
Diarrhea  1  30/123 (24.39%)  47 35/109 (32.11%)  88 39/137 (28.47%)  60 6/31 (19.35%)  15
Dry mouth  1  4/123 (3.25%)  6 4/109 (3.67%)  10 1/137 (0.73%)  1 1/31 (3.23%)  1
Duodenal hemorrhage  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Duodenal ulcer  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Dyspepsia  1  6/123 (4.88%)  17 15/109 (13.76%)  24 10/137 (7.30%)  24 2/31 (6.45%)  3
Dysphagia  1  2/123 (1.63%)  9 1/109 (0.92%)  1 5/137 (3.65%)  6 0/31 (0.00%)  0
Ear, nose and throat examination abnormal  1  1/123 (0.81%)  2 6/109 (5.50%)  17 4/137 (2.92%)  5 1/31 (3.23%)  1
Esophagitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Flatulence  1  1/123 (0.81%)  2 3/109 (2.75%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
Gastric hemorrhage  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Gastritis  1  2/123 (1.63%)  3 2/109 (1.83%)  2 3/137 (2.19%)  3 0/31 (0.00%)  0
Gastrointestinal disorder  1  6/123 (4.88%)  6 3/109 (2.75%)  3 3/137 (2.19%)  3 0/31 (0.00%)  0
Gastrointestinal pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Gingival pain  1  0/123 (0.00%)  0 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Hemorrhoids  1  4/123 (3.25%)  15 3/109 (2.75%)  4 4/137 (2.92%)  8 0/31 (0.00%)  0
Lower gastrointestinal hemorrhage  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Mucositis oral  1  8/123 (6.50%)  11 6/109 (5.50%)  10 2/137 (1.46%)  2 0/31 (0.00%)  0
Nausea  1  64/123 (52.03%)  158 57/109 (52.29%)  155 79/137 (57.66%)  197 22/31 (70.97%)  50
Oral hemorrhage  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Oral pain  1  0/123 (0.00%)  0 2/109 (1.83%)  3 1/137 (0.73%)  3 0/31 (0.00%)  0
Pancreatitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Peritoneal pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Proctitis  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Rectal hemorrhage  1  1/123 (0.81%)  2 0/109 (0.00%)  0 3/137 (2.19%)  3 0/31 (0.00%)  0
Rectal pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  9 0/31 (0.00%)  0
Salivary gland disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Stomach pain  1  2/123 (1.63%)  2 3/109 (2.75%)  10 1/137 (0.73%)  1 1/31 (3.23%)  1
Tooth disorder  1  1/123 (0.81%)  1 2/109 (1.83%)  2 3/137 (2.19%)  3 0/31 (0.00%)  0
Toothache  1  3/123 (2.44%)  5 3/109 (2.75%)  6 3/137 (2.19%)  4 0/31 (0.00%)  0
Vomiting  1  23/123 (18.70%)  41 17/109 (15.60%)  31 47/137 (34.31%)  74 5/31 (16.13%)  9
General disorders         
Chest pain  1  13/123 (10.57%)  14 13/109 (11.93%)  19 21/137 (15.33%)  30 1/31 (3.23%)  1
Chills  1  39/123 (31.71%)  50 39/109 (35.78%)  57 44/137 (32.12%)  61 5/31 (16.13%)  6
Edema limbs  1  15/123 (12.20%)  31 20/109 (18.35%)  41 20/137 (14.60%)  49 3/31 (9.68%)  10
Facial pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Fatigue  1  89/123 (72.36%)  401 90/109 (82.57%)  481 106/137 (77.37%)  408 24/31 (77.42%)  119
Fever  1  19/123 (15.45%)  20 23/109 (21.10%)  27 23/137 (16.79%)  29 7/31 (22.58%)  8
Flu-like symptoms  1  0/123 (0.00%)  0 6/109 (5.50%)  10 4/137 (2.92%)  5 2/31 (6.45%)  2
Gait abnormal  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
General symptom  1  3/123 (2.44%)  3 1/109 (0.92%)  1 3/137 (2.19%)  6 0/31 (0.00%)  0
Injection site reaction  1  1/123 (0.81%)  1 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Irritability  1  0/123 (0.00%)  0 1/109 (0.92%)  3 1/137 (0.73%)  1 1/31 (3.23%)  4
Localized edema  1  3/123 (2.44%)  3 4/109 (3.67%)  4 10/137 (7.30%)  14 1/31 (3.23%)  2
Pain  1  12/123 (9.76%)  16 18/109 (16.51%)  38 19/137 (13.87%)  26 1/31 (3.23%)  1
Pericardial pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis  1  2/123 (1.63%)  2 1/109 (0.92%)  1 2/137 (1.46%)  3 0/31 (0.00%)  0
Gallbladder pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Hepatic failure  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Immune system disorders         
Autoimmune disorder  1  2/123 (1.63%)  4 0/109 (0.00%)  0 2/137 (1.46%)  4 0/31 (0.00%)  0
Cytokine release syndrome  1  6/123 (4.88%)  6 5/109 (4.59%)  5 3/137 (2.19%)  3 1/31 (3.23%)  1
Hypersensitivity  1  7/123 (5.69%)  7 11/109 (10.09%)  16 11/137 (8.03%)  13 2/31 (6.45%)  2
Immune system disorder  1  1/123 (0.81%)  1 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Infections and infestations         
Abdominal infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anorectal infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Appendicitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Bladder infection  1  3/123 (2.44%)  3 2/109 (1.83%)  2 2/137 (1.46%)  3 1/31 (3.23%)  1
Bone infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Bronchitis  1  9/123 (7.32%)  11 11/109 (10.09%)  13 5/137 (3.65%)  7 1/31 (3.23%)  1
Catheter related infection  1  3/123 (2.44%)  5 0/109 (0.00%)  0 4/137 (2.92%)  4 1/31 (3.23%)  1
Colitis, infectious (e.g., Clostridium difficile)  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Conjunctivitis infective  1  1/123 (0.81%)  1 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Corneal infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Esophageal infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Eye infection  1  0/123 (0.00%)  0 3/109 (2.75%)  4 1/137 (0.73%)  5 1/31 (3.23%)  1
Eye infection intraocular  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Gallbladder infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Gastric infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Gingival infection  1  0/123 (0.00%)  0 2/109 (1.83%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Hepatic infection  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Infection  1  7/123 (5.69%)  16 9/109 (8.26%)  12 4/137 (2.92%)  5 1/31 (3.23%)  1
Infection with unknown ANC  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Infectious meningitis  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Joint infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 0/137 (0.00%)  0 1/31 (3.23%)  1
Laryngitis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Lip infection  1  2/123 (1.63%)  3 4/109 (3.67%)  5 3/137 (2.19%)  3 0/31 (0.00%)  0
Mucosal infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Nail infection  1  0/123 (0.00%)  0 1/109 (0.92%)  5 2/137 (1.46%)  4 0/31 (0.00%)  0
Opportunistic infection  1  1/123 (0.81%)  1 1/109 (0.92%)  2 3/137 (2.19%)  10 0/31 (0.00%)  0
Otitis externa  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Otitis media  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Penile infection  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Peripheral nerve infection  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Pharyngitis  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pneumonia  1  8/123 (6.50%)  10 8/109 (7.34%)  9 5/137 (3.65%)  5 2/31 (6.45%)  2
Rhinitis infective  1  1/123 (0.81%)  1 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Salivary gland infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Sepsis  1  2/123 (1.63%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Sinusitis  1  13/123 (10.57%)  18 12/109 (11.01%)  24 8/137 (5.84%)  11 0/31 (0.00%)  0
Skin infection  1  8/123 (6.50%)  9 7/109 (6.42%)  10 8/137 (5.84%)  10 1/31 (3.23%)  1
Small intestine infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Soft tissue infection  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Tooth infection  1  3/123 (2.44%)  3 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Tracheitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Upper aerodigestive tract infection  1  2/123 (1.63%)  2 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Upper respiratory infection  1  15/123 (12.20%)  20 13/109 (11.93%)  21 12/137 (8.76%)  14 2/31 (6.45%)  3
Ureteritis  1  10/123 (8.13%)  13 8/109 (7.34%)  9 9/137 (6.57%)  13 1/31 (3.23%)  2
Urinary tract infection  1  3/123 (2.44%)  5 6/109 (5.50%)  8 9/137 (6.57%)  12 1/31 (3.23%)  1
Vaginal infection  1  1/123 (0.81%)  1 4/109 (3.67%)  4 1/137 (0.73%)  1 0/31 (0.00%)  0
Viral hepatitis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Vulvitis  1  1/123 (0.81%)  3 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Wound infection  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Injury, poisoning and procedural complications         
Bruising  1  1/123 (0.81%)  1 6/109 (5.50%)  20 6/137 (4.38%)  6 1/31 (3.23%)  1
Fracture  1  3/123 (2.44%)  3 3/109 (2.75%)  7 1/137 (0.73%)  1 0/31 (0.00%)  0
Intraoperative neurological injury - NERVES: Sciatic  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Seroma  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  3 0/31 (0.00%)  0
Thermal burn  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Vascular access complication  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Venous injury - Extremity-upper  1  1/123 (0.81%)  1 1/109 (0.92%)  4 0/137 (0.00%)  0 0/31 (0.00%)  0
Wound dehiscence  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Investigations         
Activated partial thromboplastin time prolonged  1  1/123 (0.81%)  1 3/109 (2.75%)  4 1/137 (0.73%)  4 0/31 (0.00%)  0
Alanine aminotransferase increased  1  28/123 (22.76%)  74 29/109 (26.61%)  89 33/137 (24.09%)  89 7/31 (22.58%)  19
Alkaline phosphatase increased  1  19/123 (15.45%)  39 15/109 (13.76%)  42 23/137 (16.79%)  50 4/31 (12.90%)  4
Amylase increased  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Aspartate aminotransferase increased  1  31/123 (25.20%)  67 33/109 (30.28%)  76 33/137 (24.09%)  72 7/31 (22.58%)  13
Blood bilirubin increased  1  24/123 (19.51%)  59 17/109 (15.60%)  49 9/137 (6.57%)  9 4/31 (12.90%)  19
CD4 lymphocytes decreased  1  1/123 (0.81%)  1 3/109 (2.75%)  3 4/137 (2.92%)  7 1/31 (3.23%)  6
Cardiac troponin I increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Creatine phosphokinase increased  1  1/123 (0.81%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Creatinine increased  1  22/123 (17.89%)  34 18/109 (16.51%)  34 19/137 (13.87%)  39 2/31 (6.45%)  3
Electrocardiogram QTc interval prolonged  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  3 0/31 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Haptoglobin decreased  1  1/123 (0.81%)  1 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
INR increased  1  2/123 (1.63%)  4 2/109 (1.83%)  3 6/137 (4.38%)  18 0/31 (0.00%)  0
Laboratory test abnormal  1  8/123 (6.50%)  22 8/109 (7.34%)  20 11/137 (8.03%)  30 3/31 (9.68%)  3
Leukocyte count decreased  1  64/123 (52.03%)  258 61/109 (55.96%)  271 64/137 (46.72%)  273 14/31 (45.16%)  67
Lipase increased  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Lymphocyte count decreased  1  49/123 (39.84%)  225 48/109 (44.04%)  216 55/137 (40.15%)  281 10/31 (32.26%)  58
Neutrophil count decreased  1  100/123 (81.30%)  356 97/109 (88.99%)  420 109/137 (79.56%)  370 28/31 (90.32%)  106
Platelet count decreased  1  95/123 (77.24%)  528 85/109 (77.98%)  470 114/137 (83.21%)  546 22/31 (70.97%)  116
Serum cholesterol increased  1  2/123 (1.63%)  2 2/109 (1.83%)  5 2/137 (1.46%)  7 0/31 (0.00%)  0
Weight gain  1  13/123 (10.57%)  31 13/109 (11.93%)  21 12/137 (8.76%)  29 1/31 (3.23%)  1
Weight loss  1  5/123 (4.07%)  5 12/109 (11.01%)  15 10/137 (7.30%)  16 3/31 (9.68%)  3
Metabolism and nutrition disorders         
Acidosis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Alkalosis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Anorexia  1  23/123 (18.70%)  41 28/109 (25.69%)  49 20/137 (14.60%)  26 7/31 (22.58%)  16
Blood bicarbonate decreased  1  1/123 (0.81%)  1 2/109 (1.83%)  2 5/137 (3.65%)  6 0/31 (0.00%)  0
Blood glucose increased  1  54/123 (43.90%)  185 54/109 (49.54%)  217 62/137 (45.26%)  212 10/31 (32.26%)  39
Blood uric acid increased  1  7/123 (5.69%)  12 9/109 (8.26%)  22 10/137 (7.30%)  16 0/31 (0.00%)  0
Dehydration  1  2/123 (1.63%)  4 2/109 (1.83%)  6 2/137 (1.46%)  2 1/31 (3.23%)  1
Glucose intolerance  1  1/123 (0.81%)  3 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Iron overload  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Obesity  1  0/123 (0.00%)  0 0/109 (0.00%)  0 3/137 (2.19%)  11 0/31 (0.00%)  0
Serum albumin decreased  1  15/123 (12.20%)  23 23/109 (21.10%)  43 20/137 (14.60%)  29 4/31 (12.90%)  12
Serum calcium decreased  1  31/123 (25.20%)  59 42/109 (38.53%)  78 38/137 (27.74%)  68 7/31 (22.58%)  20
Serum calcium increased  1  4/123 (3.25%)  7 5/109 (4.59%)  10 2/137 (1.46%)  8 0/31 (0.00%)  0
Serum glucose decreased  1  6/123 (4.88%)  14 5/109 (4.59%)  12 8/137 (5.84%)  10 1/31 (3.23%)  2
Serum magnesium decreased  1  3/123 (2.44%)  5 6/109 (5.50%)  14 6/137 (4.38%)  7 1/31 (3.23%)  1
Serum magnesium increased  1  1/123 (0.81%)  1 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Serum phosphate decreased  1  12/123 (9.76%)  23 15/109 (13.76%)  36 8/137 (5.84%)  13 3/31 (9.68%)  5
Serum potassium decreased  1  16/123 (13.01%)  33 19/109 (17.43%)  35 22/137 (16.06%)  36 3/31 (9.68%)  4
Serum potassium increased  1  11/123 (8.94%)  13 10/109 (9.17%)  14 12/137 (8.76%)  15 1/31 (3.23%)  2
Serum sodium decreased  1  21/123 (17.07%)  40 28/109 (25.69%)  46 23/137 (16.79%)  44 3/31 (9.68%)  3
Serum sodium increased  1  7/123 (5.69%)  8 1/109 (0.92%)  1 2/137 (1.46%)  5 0/31 (0.00%)  0
Serum triglycerides increased  1  3/123 (2.44%)  3 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Tumor lysis syndrome  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  24/123 (19.51%)  65 24/109 (22.02%)  57 24/137 (17.52%)  53 3/31 (9.68%)  5
Arthritis  1  2/123 (1.63%)  5 3/109 (2.75%)  4 6/137 (4.38%)  13 1/31 (3.23%)  1
Back pain  1  22/123 (17.89%)  28 21/109 (19.27%)  57 23/137 (16.79%)  44 3/31 (9.68%)  4
Bone pain  1  7/123 (5.69%)  11 7/109 (6.42%)  8 7/137 (5.11%)  11 1/31 (3.23%)  1
Buttock pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 4/137 (2.92%)  6 0/31 (0.00%)  0
Chest wall pain  1  2/123 (1.63%)  3 0/109 (0.00%)  0 4/137 (2.92%)  6 1/31 (3.23%)  1
Fibrosis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Fibrosis deep connective tissue  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Joint disorder  1  3/123 (2.44%)  11 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Joint effusion  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Muscle weakness  1  6/123 (4.88%)  11 10/109 (9.17%)  12 3/137 (2.19%)  10 2/31 (6.45%)  3
Muscle weakness lower limb  1  1/123 (0.81%)  2 5/109 (4.59%)  11 1/137 (0.73%)  2 0/31 (0.00%)  0
Muscle weakness right-sided  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Muscle weakness upper limb  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  2 0/31 (0.00%)  0
Musculoskeletal disorder  1  0/123 (0.00%)  0 5/109 (4.59%)  6 5/137 (3.65%)  7 2/31 (6.45%)  2
Myalgia  1  17/123 (13.82%)  31 15/109 (13.76%)  43 16/137 (11.68%)  25 4/31 (12.90%)  5
Myositis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Neck pain  1  7/123 (5.69%)  9 5/109 (4.59%)  8 11/137 (8.03%)  20 2/31 (6.45%)  2
Neck soft tissue necrosis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Osteoporosis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  3 0/31 (0.00%)  0
Pain in extremity  1  17/123 (13.82%)  34 18/109 (16.51%)  39 16/137 (11.68%)  33 0/31 (0.00%)  0
Trismus  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 0/31 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Treatment related secondary malignancy  1  3/123 (2.44%)  3 2/109 (1.83%)  2 1/137 (0.73%)  1 3/31 (9.68%)  3
Tumor flare  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 1/31 (3.23%)  2
Tumor pain  1  4/123 (3.25%)  4 8/109 (7.34%)  16 5/137 (3.65%)  8 0/31 (0.00%)  0
Nervous system disorders         
Acoustic nerve disorder NOS  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Ataxia  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Cerebrospinal fluid leakage  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Cognitive disturbance  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 1/31 (3.23%)  5
Depressed level of consciousness  1  1/123 (0.81%)  1 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Dizziness  1  17/123 (13.82%)  33 25/109 (22.94%)  49 19/137 (13.87%)  32 2/31 (6.45%)  5
Dysgeusia  1  9/123 (7.32%)  14 12/109 (11.01%)  19 5/137 (3.65%)  6 1/31 (3.23%)  4
Encephalopathy  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Extrapyramidal disorder  1  1/123 (0.81%)  1 2/109 (1.83%)  3 3/137 (2.19%)  3 1/31 (3.23%)  2
Headache  1  33/123 (26.83%)  62 35/109 (32.11%)  72 27/137 (19.71%)  60 8/31 (25.81%)  22
Memory impairment  1  3/123 (2.44%)  3 3/109 (2.75%)  22 5/137 (3.65%)  9 1/31 (3.23%)  1
Neuralgia  1  0/123 (0.00%)  0 2/109 (1.83%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Neurological disorder NOS  1  4/123 (3.25%)  6 5/109 (4.59%)  10 7/137 (5.11%)  12 1/31 (3.23%)  1
Nystagmus  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Peripheral motor neuropathy  1  0/123 (0.00%)  0 2/109 (1.83%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Peripheral sensory neuropathy  1  18/123 (14.63%)  39 20/109 (18.35%)  69 17/137 (12.41%)  56 2/31 (6.45%)  3
Phrenic nerve paralysis  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Seizure  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Sinus pain  1  4/123 (3.25%)  4 3/109 (2.75%)  6 2/137 (1.46%)  2 0/31 (0.00%)  0
Speech disorder  1  2/123 (1.63%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Syncope  1  0/123 (0.00%)  0 3/109 (2.75%)  3 0/137 (0.00%)  0 0/31 (0.00%)  0
Tremor  1  3/123 (2.44%)  4 3/109 (2.75%)  4 0/137 (0.00%)  0 1/31 (3.23%)  1
Psychiatric disorders         
Agitation  1  0/123 (0.00%)  0 3/109 (2.75%)  10 3/137 (2.19%)  4 0/31 (0.00%)  0
Anxiety  1  14/123 (11.38%)  38 17/109 (15.60%)  27 13/137 (9.49%)  22 2/31 (6.45%)  4
Confusion  1  1/123 (0.81%)  2 2/109 (1.83%)  3 1/137 (0.73%)  1 0/31 (0.00%)  0
Depression  1  8/123 (6.50%)  35 11/109 (10.09%)  23 9/137 (6.57%)  16 2/31 (6.45%)  18
Euphoria  1  0/123 (0.00%)  0 2/109 (1.83%)  8 0/137 (0.00%)  0 0/31 (0.00%)  0
Insomnia  1  19/123 (15.45%)  45 23/109 (21.10%)  52 25/137 (18.25%)  55 5/31 (16.13%)  12
Libido decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  6 1/137 (0.73%)  1 0/31 (0.00%)  0
Renal and urinary disorders         
Cystitis  1  0/123 (0.00%)  0 2/109 (1.83%)  5 3/137 (2.19%)  3 0/31 (0.00%)  0
Glomerular filtration rate decreased  1  0/123 (0.00%)  0 1/109 (0.92%)  1 4/137 (2.92%)  7 0/31 (0.00%)  0
Hemorrhage urinary tract  1  1/123 (0.81%)  1 5/109 (4.59%)  10 2/137 (1.46%)  2 0/31 (0.00%)  0
Kidney pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Proteinuria  1  1/123 (0.81%)  1 6/109 (5.50%)  7 1/137 (0.73%)  1 0/31 (0.00%)  0
Renal failure  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Urethral pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Urinary frequency  1  6/123 (4.88%)  15 9/109 (8.26%)  17 12/137 (8.76%)  21 2/31 (6.45%)  2
Urinary incontinence  1  0/123 (0.00%)  0 3/109 (2.75%)  3 4/137 (2.92%)  16 0/31 (0.00%)  0
Urinary retention  1  3/123 (2.44%)  4 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Urine discoloration  1  0/123 (0.00%)  0 0/109 (0.00%)  0 2/137 (1.46%)  2 1/31 (3.23%)  1
Urogenital disorder  1  5/123 (4.07%)  9 4/109 (3.67%)  10 5/137 (3.65%)  15 2/31 (6.45%)  3
Reproductive system and breast disorders         
Breast pain  1  2/123 (1.63%)  2 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Erectile dysfunction  1  0/123 (0.00%)  0 2/109 (1.83%)  7 0/137 (0.00%)  0 0/31 (0.00%)  0
Pelvic pain  1  1/123 (0.81%)  2 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Perineal pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Prostatic obstruction  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Reproductive tract disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Scrotal pain  1  1/123 (0.81%)  1 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Testicular pain  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Vaginal dryness  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Vaginal hemorrhage  1  0/123 (0.00%)  0 1/109 (0.92%)  1 1/137 (0.73%)  1 0/31 (0.00%)  0
Vaginal pain  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Adult respiratory distress syndrome  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Allergic rhinitis  1  18/123 (14.63%)  48 18/109 (16.51%)  42 13/137 (9.49%)  24 1/31 (3.23%)  3
Aspiration  1  1/123 (0.81%)  1 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Atelectasis  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Bronchospasm  1  2/123 (1.63%)  2 0/109 (0.00%)  0 3/137 (2.19%)  7 0/31 (0.00%)  0
Cough  1  30/123 (24.39%)  69 48/109 (44.04%)  122 44/137 (32.12%)  91 8/31 (25.81%)  11
Dyspnea  1  32/123 (26.02%)  102 43/109 (39.45%)  104 43/137 (31.39%)  90 9/31 (29.03%)  22
Epistaxis  1  2/123 (1.63%)  2 3/109 (2.75%)  8 4/137 (2.92%)  7 0/31 (0.00%)  0
Hiccups  1  1/123 (0.81%)  1 2/109 (1.83%)  2 4/137 (2.92%)  6 0/31 (0.00%)  0
Hypoxia  1  0/123 (0.00%)  0 2/109 (1.83%)  2 1/137 (0.73%)  1 2/31 (6.45%)  2
Nasal congestion  1  7/123 (5.69%)  9 2/109 (1.83%)  2 2/137 (1.46%)  2 0/31 (0.00%)  0
Pharyngeal hemorrhage  1  1/123 (0.81%)  1 0/109 (0.00%)  0 0/137 (0.00%)  0 0/31 (0.00%)  0
Pharyngeal mucositis  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Pharyngolaryngeal pain  1  7/123 (5.69%)  14 8/109 (7.34%)  19 13/137 (9.49%)  16 0/31 (0.00%)  0
Pleural effusion  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pleuritic pain  1  0/123 (0.00%)  0 1/109 (0.92%)  1 2/137 (1.46%)  2 0/31 (0.00%)  0
Pneumonitis  1  1/123 (0.81%)  1 1/109 (0.92%)  1 4/137 (2.92%)  4 0/31 (0.00%)  0
Respiratory disorder  1  5/123 (4.07%)  6 6/109 (5.50%)  10 1/137 (0.73%)  4 2/31 (6.45%)  4
Respiratory tract hemorrhage  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Voice alteration  1  1/123 (0.81%)  1 3/109 (2.75%)  5 2/137 (1.46%)  2 0/31 (0.00%)  0
Skin and subcutaneous tissue disorders         
Alopecia  1  4/123 (3.25%)  9 4/109 (3.67%)  16 3/137 (2.19%)  5 0/31 (0.00%)  0
Decubitus ulcer  1  0/123 (0.00%)  0 0/109 (0.00%)  0 0/137 (0.00%)  0 1/31 (3.23%)  1
Dry skin  1  4/123 (3.25%)  5 10/109 (9.17%)  21 6/137 (4.38%)  21 2/31 (6.45%)  5
Erythema multiforme  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Hand-and-foot syndrome  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Nail disorder  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Pain of skin  1  1/123 (0.81%)  5 2/109 (1.83%)  3 2/137 (1.46%)  2 0/31 (0.00%)  0
Petechiae  1  3/123 (2.44%)  3 0/109 (0.00%)  0 2/137 (1.46%)  3 0/31 (0.00%)  0
Pruritus  1  14/123 (11.38%)  24 20/109 (18.35%)  35 18/137 (13.14%)  25 7/31 (22.58%)  14
Rash acneiform  1  0/123 (0.00%)  0 1/109 (0.92%)  1 0/137 (0.00%)  0 0/31 (0.00%)  0
Rash desquamating  1  32/123 (26.02%)  48 49/109 (44.95%)  122 50/137 (36.50%)  99 15/31 (48.39%)  28
Scalp pain  1  0/123 (0.00%)  0 2/109 (1.83%)  2 0/137 (0.00%)  0 0/31 (0.00%)  0
Skin disorder  1  3/123 (2.44%)  3 10/109 (9.17%)  11 9/137 (6.57%)  14 4/31 (12.90%)  4
Skin hyperpigmentation  1  0/123 (0.00%)  0 0/109 (0.00%)  0 0/137 (0.00%)  0 1/31 (3.23%)  1
Skin hypopigmentation  1  0/123 (0.00%)  0 1/109 (0.92%)  4 0/137 (0.00%)  0 0/31 (0.00%)  0
Skin ulceration  1  3/123 (2.44%)  4 1/109 (0.92%)  1 0/137 (0.00%)  0 1/31 (3.23%)  1
Sweating  1  21/123 (17.07%)  52 27/109 (24.77%)  50 31/137 (22.63%)  81 6/31 (19.35%)  12
Telangiectasia  1  0/123 (0.00%)  0 0/109 (0.00%)  0 1/137 (0.73%)  1 0/31 (0.00%)  0
Urticaria  1  4/123 (3.25%)  9 4/109 (3.67%)  7 6/137 (4.38%)  8 1/31 (3.23%)  1
Vascular disorders         
Flushing  1  4/123 (3.25%)  9 7/109 (6.42%)  17 2/137 (1.46%)  2 0/31 (0.00%)  0