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Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial) (ORIGIN)

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ClinicalTrials.gov Identifier: NCT00910910
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : December 21, 2016
Last Update Posted : July 9, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition B-Cell Chronic Lymphocytic Leukemia
Interventions Drug: Lenalidomide
Drug: Chlorambucil
Enrollment 450
Recruitment Details 118 sites randomized participants in Austria, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Columbia, Croatia, Czech Republic, Denmark, Hungary, Israel, Italy, the Netherlands, New Zealand, Poland, Portugal, Romania, Russia, South Africa, Slovakia, Spain, Serbia, the United Kingdom, and the United States of America
Pre-assignment Details Participants were randomized 1:1 to lenalidomide or chlorambucil and stratified by disease stage, presence of pre-defined co-morbidities and presence of at least one of the following poor prognostic factors: 11q deletion, 17 p deletion, unmutated IgVH and B2M>4.0 mg/dL.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first. Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Period Title: Overall Study
Started 225 225
Safety Population 224 [1] 223 [1]
Completed 0 [2] 1 [2]
Not Completed 225 224
Reason Not Completed
Adverse Event             63             35
PD without histologic change             27             23
PD with histologic change             0             2
Withdrawal by Subject             7             5
Lost to Follow-up             2             2
Death             9             3
Protocol Violation             2             2
Completed 13 cycles of treatment             0             118
Other             114             32
Untreated before cycle 1             1             2
[1]
All randomized participants who received at least 1 dose of the either lenalidomide or chlorambucil
[2]
Completed includes participants who continued with ongoing treatment
Arm/Group Title Lenalidomide Chlorambucil Total
Hide Arm/Group Description For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first. Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles). Total of all reporting groups
Overall Number of Baseline Participants 225 225 450
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 225 participants 225 participants 450 participants
73.0  (5.72) 73.3  (5.72) 73.1  (5.72)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 225 participants 225 participants 450 participants
Female
93
  41.3%
83
  36.9%
176
  39.1%
Male
132
  58.7%
142
  63.1%
274
  60.9%
[1]
Measure Description: The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.
1.Primary Outcome
Title Kaplan-Meier Estimate of Progression Free Survival (PFS)
Hide Description Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator’s assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression
Time Frame From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
This is a smaller population used in this analysis (earlier cut-off date) prior to the last participant enrolled in the study. The ITT population was defined as all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 212 215
Median (95% Confidence Interval)
Unit of Measure: months
30.8 [1] 
(18.7 to NA)
23.0
(19.3 to 29.2)
[1]
Not Applicable = The upper boundary of confidence interval (CI) is not estimable because of censored participants.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments Stratification factors: Disease stage (Binet A or Binet B or Rai I or Rai II versus (VS) Binet C or Rai III or Rai IV); Presence of at least one of the co-morbidities Asparate transaminase (AST)/Alanine transaminase (ALT) ≥ 3.0 times Upper Limits of Normal (ULN,) Creatinine clearance ≥ 30 to < 60 mL/min, Yes VS No); Presence of at least one 11q deletion, 17p deletion, unmutated Immunoglobulin Heavy-chain Variable-region (IgVH) or Beta-2 Microglobulin (ß2M )> 4.0 mg/L (Yes versus No VS Unknown)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.323
Comments [Not Specified]
Method stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 90%
0.88 to 1.66
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
2.Primary Outcome
Title Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014
Hide Description Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator’s assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
Time Frame From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 225 225
Median (95% Confidence Interval)
Unit of Measure: months
30.8 [1] 
(18.7 to NA)
21.4
(19.3 to 25.1)
[1]
NA = The upper boundary of CI is not estimable because of censored participants.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments Stratification factors: Disease stage (Binet A or Binet B or Rai I or Rai II versus (VS) Binet C or Rai III or Rai IV); Presence of at least one of the co-morbidities Asparate transaminase (AST)/Alanine transaminase (ALT) ≥ 3.0 times Upper Limits of Normal (ULN,) Creatinine clearance ≥ 30 to < 60 mL/min, Yes VS No); Presence of at least one 11q deletion, 17p deletion, unmutated Immunoglobulin Heavy-chain Variable-region (IgVH) or Beta-2 Microglobulin (ß2M )> 4.0 mg/L (Yes versus No VS Unknown)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments The p-value is based on a stratified log-rank test
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.99
Confidence Interval (2-Sided) 90%
0.76 to 1.29
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
3.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time Frame From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil
Hide Outcome Measure Data
Hide Analysis Population Description
This is a smaller population used in this analysis (earlier cut-off date) prior to the last participant enrolled in the study. The safety population was defined as all randomized participants who received at least 1 dose of the study treatment (either lenalidomide or chlorambucil) as of the data cut off date of 18 Feb 2013
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 211 213
Measure Type: Number
Unit of Measure: participants
≥ 1 TEAE 202 186
≥ 1 TEAE related to study drug 183 139
≥ 1 NCI CTC Grade 3-4 TEAE 173 117
Grade 3-4 adverse event related to any study drug 143 82
≥ 1 NCI CTC Grade 5 TEAE 21 9
≥ Grade 5 adverse event related to any study drug 6 1
≥ 1 Serious TEAE 129 76
≥ 1 Serious TEAE related to any study drug 95 46
≥1 TEAE leading to stopping either study drug 61 34
≥1 Related TEAE leading to stopping either drug 39 19
4.Secondary Outcome
Title Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014
Hide Description AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time Frame From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all randomized participants who received at least 1 dose of the study treatment (either lenalidomide or chlorambucil).
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 224 223
Measure Type: Number
Unit of Measure: participants
≥ 1 TEAE 216 202
≥ 1 TEAE related to study drug 194 155
≥ 1 NCI CTC Grade 3-4 TEAE 188 131
Grade 3-4 adverse event related to any study drug 157 90
≥ 1 NCI CTC Grade 5 TEAE 21 11
≥ Grade 5 adverse event related to any study drug 6 1
≥ 1 Serious TEAE 148 90
≥ 1 Serious TEAE related to any study drug 107 53
≥1 TEAE leading to stopping either study drug 70 42
≥1 Related TEAE leading to stopping either drug 46 23
5.Secondary Outcome
Title Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
Hide Description

A best overall response rate is a CR, CRi, nPR or PR and is defined as:

Complete Remission (CR):

  • No lymphadenopathy
  • No hepatomegaly or splenomegaly
  • Absence of constitutional symptoms
  • Polymorphonuclear leukocytes ≥ 1500/ul
  • No circulating clonal B-lymphocytes
  • Platelets > 100,000/ul
  • Hemoglobin > 11.0 g/dl
  • Normocellular <30% lymphocytes, no B-lymphoid nodules;

Incomplete Clinical Response (CRi):

• CR without bone marrow biopsy confirmation.

Nodular Partial Response (nPR):

• CR with the presence of residual clonal nodules.

Partial Response (PR) requires:

  • ≥ 50% decrease in peripheral blood lymphocyte count
  • ≥ 50% reduction in lymphadenopathy
  • ≥ 50% reduction in size of liver and/or spleen
  • 1 or more of the following:
  • Polymorphonuclear leukocytes ≥ 1500/ul
  • Platelets >100,000/ul
Time Frame Up to data cut-off date of 18 Feb 2013; approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
This is a smaller population used in this analysis (earlier cut-off date) prior to the last participant enrolled in the study. The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 212 215
Measure Type: Number
Unit of Measure: percentage of participants
51.9 62.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.44 to 0.96
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014
Hide Description

A best overall response rate is a CR, CRi, nPR or PR and is defined as:

Complete Remission (CR):

  • No lymphadenopathy
  • No hepatomegaly or splenomegaly
  • Absence of constitutional symptoms
  • Polymorphonuclear leukocytes ≥ 1500/ul
  • No circulating clonal B-lymphocytes
  • Platelets > 100,000/ul
  • Hemoglobin > 11.0 g/dl
  • Normocellular <30% lymphocytes, no B-lymphoid nodules;

Incomplete Clinical Response (CRi):

• CR without bone marrow biopsy confirmation.

Nodular Partial Response:

• CR with the presence of residual clonal nodules.

Partial Response requires:

  • ≥ 50% decrease in peripheral blood lymphocyte count
  • ≥ 50% reduction in lymphadenopathy
  • ≥ 50% reduction in size of liver and/or spleen
  • 1 or more of the following:
  • Polymorphonuclear leukocytes ≥ 1500/ul
  • Platelets >100,000/ul
Time Frame Up to data cut-off of 31 March 2014; approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat population was defined as all participants who were randomized, independent of whether they received study treatment or not
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 225 225
Measure Type: Number
Unit of Measure: percentage of participants with response
60.9 70.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.45 to 0.98
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Kaplan-Meier Estimate for Duration of Response
Hide Description Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had withdrawn consent or were lost to follow-up prior to documentation of progression
Time Frame Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population with an objective response as of 18 Feb 2013; includes responders
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 110 134
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(131.1 to NA)
105.3
(77.4 to 123.7)
[1]
NA = The median and upper limit of the CI not estimable due to insufficient number of participants with events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.826
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 90%
0.58 to 1.52
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups
8.Secondary Outcome
Title Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014
Hide Description Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) patients who had not progressed at the time of analysis; 2) patients who had withdrawn consent or were lost to follow-up prior to documentation of progression
Time Frame Up to data cut-off of 31 March 2014; up to approximately 53 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population with an objective response as of 31 March 2014; includes responders.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 137 158
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(149.4 to NA)
87.1
(77.1 to 108.7)
[1]
NA due to large number of censored observations.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.149
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.71
Confidence Interval (2-Sided) 90%
0.48 to 1.05
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
9.Secondary Outcome
Title Time to Response
Hide Description Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines
Time Frame Up to data cut-off of 18 Feb 2013; up to approximately 39 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT participants with an objective response as of 18 February 2013
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 110 134
Median (Full Range)
Unit of Measure: weeks
8.6
(3.7 to 104.3)
8.1
(3.7 to 52.7)
10.Secondary Outcome
Title Time to Response for a Later Cut-off Date of 31 March 2014
Hide Description Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines
Time Frame Up to data cut-off of 31 March 2014; up to approximately 53 months
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Hide Analysis Population Description
ITT participants who had not progressed at the time of analysis; or those who had withdrawn consent or were lost to follow-up prior to documentation of progression.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 137 158
Median (Full Range)
Unit of Measure: weeks
10.4
(3.7 to 136.1)
8.1
(3.7 to 68.7)
11.Secondary Outcome
Title Kaplan Meier Estimate of Overall Survival
Hide Description Overall Survival is defined as the time between randomization and death from any cause.
Time Frame Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 225 225
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
44.0 [2] 
(37.3 to NA)
[1]
The median had not been reached and CI not estimable because of small number of events. .
[2]
Upper level CI not estimable because of small number of events
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.03
Confidence Interval (2-Sided) 90%
0.73 to 1.46
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
12.Secondary Outcome
Title Kaplan Meier Estimate for Overall Survival at the Final Analysis
Hide Description Overall Survival is defined as the time between randomization and death from any cause. Overall survival was censored at the last date that the subject was known to be alive for participants who were alive as of the data cutoff date and for participants who were lost to follow-up before death was documented.
Time Frame Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized, independent of whether they received study treatment.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 225 225
Median (95% Confidence Interval)
Unit of Measure: Months
74.3
(58.5 to 84.4)
70.5 [1] 
(57.1 to NA)
[1]
Upper CI not estimable because of censored observations.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Chlorambucil
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.709
Comments [Not Specified]
Method stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.06
Confidence Interval (2-Sided) 90%
0.83 to 1.34
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups
13.Secondary Outcome
Title Functional Assessment of Cancer Therapy-General to Create the FACT-Leukemia (FACT-Leu) Quality of Life Instrument
Hide Description The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease. The FACT-Leu is described as including 27 items that assess 17 physical symptoms (fevers, bleeding, general pain, stomach pain, chills, night sweats, bruising, lymph node swelling, weakness, tiredness, weight loss, appetite, shortness of breath, functional ability, diarrhea, concentration, and mouth sores) and 10 emotional/social concerns (frustration with activity limitation, discouraged by illness, future planning, uncertainty, worry about illness, emotional lability, isolation, infertility concern, family worry, and worry about infections).
Time Frame Day 1 and once every 8 weeks
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Hide Analysis Population Description
No data were collected for the FACT-Leu QOL assessment. Analysis was not conducted due to the discontinuation of the lenalidomide arm.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Euro Quality of Life Five Dimension (EQ-5D) Questionnaire
Hide Description The standardized extended version of EQ-5D was designed for the collection of health state values using a visual analogue scale (VAS) rating scale - a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
Time Frame Day 1 and once every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No data were collected for the EQ-5D QOL assessment. The EQ-5D analysis was not conducted due to the discontinuation of the lenalidomide arm.
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment
Hide Description Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil)
Time Frame Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all randomized participants who received at least 1 dose of the study treatment (either lenalidomide or chlorambucil).
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 224 223
Measure Type: Number
Unit of Measure: participants
Participants receiving additional CLL therapy 125 120
Participants receiving alkylating agents 107 106
Participants receiving antineoplastic aents 93 86
Participants receiving antimetabolites 34 24
Participants receiving corticosteroids 27 16
Participants receiving plant alkaloids 22 11
Participants receiving cytotoxic antibiotics 10 3
Participants receiving immunosuppressants 3 2
Participants receiving therapeutic products 4 3
Participants receiving other unspecified products 0 2
Antihistamine For Systemic Use 1 1
Drugs for Peptic ulcer and Gastric Reflex 1 0
Immunoglobulins 1 2
Other Analgesics and Antipyretics 1 1
Specific Antirheumatic Agents 1 0
Antiemetics and Antinauseants 0 1
Corticosteriods for Systemic Use 0 1
Immunostimulants 0 1
16.Other Pre-specified Outcome
Title Number of Participants Deaths During the Treatment and Survival Follow-Up Phase
Hide Description The number of study participants deaths during the treatment and follow-up phase
Time Frame From the first dose of study drug up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants who were randomized, independent of whether they received study treatment or not
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description:
For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first.
Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Overall Number of Participants Analyzed 225 225
Measure Type: Number
Unit of Measure: Participants
101 95
Time Frame All AEs were recorded by the Investigator(s) from first dose of study drug to 30 days after the treatment discontinuation visit. The median treatment duration was 263 days for lenalidomide and 362 days for chlorambucil.
Adverse Event Reporting Description Secondary Primary Malignancies (SPMs) were monitored and reported as SAEs regardless of the treatment arm the participant was is on. SPMs were reported from the time of signing the informed consent up to and including the survival follow-up period. Participants were followed for at least 5 years from the date the last participant was randomized.
 
Arm/Group Title Lenalidomide Chlorambucil
Hide Arm/Group Description For participants with normal renal function [defined as Creatinine Clearance (CrCL ) ≥ 60 mL/min], 5 mg lenalidomide was administered by mouth (PO) once daily (QD) on Days 1 through 28 of the first 28-day cycle, 10 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 15 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until progressive disease (PD) or unacceptable toxicity, whichever occurred first. For participants with moderate renal impairment (defined as CrCL ≥ 30 to < 60 mL/min), 2.5 mg lenalidomide PO QD on Days 1 through 28 of the first 28-day cycle, 5 mg lenalidomide PO QD on Days 1 through 28 starting at cycle 2, 7.5 mg lenalidomide PO QD starting at cycle 3 and for the remainder of the study until PD or unacceptable toxicity, whichever occurred first. Chlorambucil oral tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months
All-Cause Mortality
Lenalidomide Chlorambucil
Affected / at Risk (%) Affected / at Risk (%)
Total   100/224 (44.64%)   93/223 (41.70%) 
Show Serious Adverse Events Hide Serious Adverse Events
Lenalidomide Chlorambucil
Affected / at Risk (%) Affected / at Risk (%)
Total   148/224 (66.07%)   90/223 (40.36%) 
Blood and lymphatic system disorders     
AGRANULOCYTOSIS  1  0/224 (0.00%)  1/223 (0.45%) 
ANAEMIA  1  18/224 (8.04%)  10/223 (4.48%) 
AUTOIMMUNE HAEMOLYTIC ANAEMIA  1  3/224 (1.34%)  4/223 (1.79%) 
FEBRILE NEUTROPENIA  1  7/224 (3.13%)  3/223 (1.35%) 
HAEMOLYTIC ANAEMIA  1  1/224 (0.45%)  0/223 (0.00%) 
IDIOPATHIC THROMBOCYTOPENIC PURPURA  1  1/224 (0.45%)  0/223 (0.00%) 
LYMPHOPENIA  1  0/224 (0.00%)  1/223 (0.45%) 
NEUTROPENIA  1  54/224 (24.11%)  33/223 (14.80%) 
PANCYTOPENIA  1  0/224 (0.00%)  1/223 (0.45%) 
SPLENIC HAEMORRHAGE  1  1/224 (0.45%)  0/223 (0.00%) 
THROMBOCYTOPENIA  1  19/224 (8.48%)  13/223 (5.83%) 
Cardiac disorders     
ANGINA PECTORIS  1  1/224 (0.45%)  0/223 (0.00%) 
ATRIAL FIBRILLATION  1  3/224 (1.34%)  1/223 (0.45%) 
ATRIAL FLUTTER  1  0/224 (0.00%)  1/223 (0.45%) 
ATRIOVENTRICULAR BLOCK COMPLETE  1  1/224 (0.45%)  0/223 (0.00%) 
ATRIOVENTRICULAR BLOCK FIRST DEGREE  1  1/224 (0.45%)  0/223 (0.00%) 
BRADYCARDIA  1  1/224 (0.45%)  0/223 (0.00%) 
CARDIAC ARREST  1  4/224 (1.79%)  0/223 (0.00%) 
CARDIAC FAILURE  1  1/224 (0.45%)  1/223 (0.45%) 
CARDIAC FAILURE ACUTE  1  1/224 (0.45%)  0/223 (0.00%) 
CARDIAC FAILURE CONGESTIVE  1  4/224 (1.79%)  0/223 (0.00%) 
CARDIOPULMONARY FAILURE  1  3/224 (1.34%)  0/223 (0.00%) 
CONGESTIVE CARDIOMYOPATHY  1  1/224 (0.45%)  0/223 (0.00%) 
PERICARDIAL EFFUSION  1  1/224 (0.45%)  0/223 (0.00%) 
SICK SINUS SYNDROME  1  2/224 (0.89%)  0/223 (0.00%) 
VENTRICULAR TACHYCARDIA  1  0/224 (0.00%)  1/223 (0.45%) 
CARDIOGENIC SHOCK  1  1/224 (0.45%)  0/223 (0.00%) 
CORONARY ARTERY DISEASE  1  1/224 (0.45%)  0/223 (0.00%) 
MYOCARDIAL INFARCTION  1  3/224 (1.34%)  0/223 (0.00%) 
Eye disorders     
DIPLOPIA  1  0/224 (0.00%)  1/223 (0.45%) 
MACULOPATHY  1  1/224 (0.45%)  0/223 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION  1  0/224 (0.00%)  1/223 (0.45%) 
ABDOMINAL PAIN  1  1/224 (0.45%)  2/223 (0.90%) 
COLITIS  1  1/224 (0.45%)  0/223 (0.00%) 
DIARRHOEA  1  1/224 (0.45%)  0/223 (0.00%) 
FEMORAL HERNIA  1  1/224 (0.45%)  0/223 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE  1  0/224 (0.00%)  2/223 (0.90%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/224 (0.00%)  1/223 (0.45%) 
NAUSEA  1  1/224 (0.45%)  2/223 (0.90%) 
SMALL INTESTINAL OBSTRUCTION  1  0/224 (0.00%)  1/223 (0.45%) 
VOMITING  1  0/224 (0.00%)  3/223 (1.35%) 
ABDOMINAL PAIN LOWER  1  1/224 (0.45%)  0/223 (0.00%) 
General disorders     
ASTHENIA  1  0/224 (0.00%)  3/223 (1.35%) 
FATIGUE  1  2/224 (0.89%)  2/223 (0.90%) 
MULTI-ORGAN FAILURE  1  3/224 (1.34%)  0/223 (0.00%) 
OEDEMA PERIPHERAL  1  2/224 (0.89%)  0/223 (0.00%) 
PAIN  1  0/224 (0.00%)  1/223 (0.45%) 
PYREXIA  1  10/224 (4.46%)  6/223 (2.69%) 
SUDDEN CARDIAC DEATH  1  0/224 (0.00%)  1/223 (0.45%) 
Hepatobiliary disorders     
CHOLECYSTITIS  1  1/224 (0.45%)  1/223 (0.45%) 
CHOLECYSTITIS ACUTE  1  2/224 (0.89%)  0/223 (0.00%) 
CHOLECYSTITIS CHRONIC  1  1/224 (0.45%)  0/223 (0.00%) 
CHOLELITHIASIS  1  0/224 (0.00%)  2/223 (0.90%) 
HEPATIC FUNCTION ABNORMAL  1  1/224 (0.45%)  0/223 (0.00%) 
HEPATITIS TOXIC  1  1/224 (0.45%)  0/223 (0.00%) 
Immune system disorders     
DRUG HYPERSENSITIVITY  1  1/224 (0.45%)  0/223 (0.00%) 
Infections and infestations     
ANAL ABSCESS  1  1/224 (0.45%)  0/223 (0.00%) 
ARTHRITIS BACTERIAL  1  0/224 (0.00%)  1/223 (0.45%) 
ARTHRITIS INFECTIVE  1  1/224 (0.45%)  0/223 (0.00%) 
BRONCHITIS  1  2/224 (0.89%)  1/223 (0.45%) 
BRONCHITIS BACTERIAL  1  0/224 (0.00%)  1/223 (0.45%) 
BRONCHOPNEUMONIA  1  2/224 (0.89%)  1/223 (0.45%) 
CELLULITIS  1  2/224 (0.89%)  3/223 (1.35%) 
CELLULITIS STAPHYLOCOCCAL  1  0/224 (0.00%)  1/223 (0.45%) 
DIARRHOEA INFECTIOUS  1  1/224 (0.45%)  0/223 (0.00%) 
ENTEROBACTER SEPSIS  1  0/224 (0.00%)  1/223 (0.45%) 
ERYSIPELAS  1  1/224 (0.45%)  1/223 (0.45%) 
ESCHERICHIA SEPSIS  1  0/224 (0.00%)  1/223 (0.45%) 
GASTROENTERITIS  1  0/224 (0.00%)  1/223 (0.45%) 
HERPES ZOSTER  1  1/224 (0.45%)  0/223 (0.00%) 
LOCALISED INFECTION  1  0/224 (0.00%)  1/223 (0.45%) 
LOWER RESPIRATORY TRACT INFECTION  1  3/224 (1.34%)  1/223 (0.45%) 
LUNG INFECTION  1  2/224 (0.89%)  0/223 (0.00%) 
NEUTROPENIC SEPSIS  1  0/224 (0.00%)  1/223 (0.45%) 
PELVIC INFECTION  1  1/224 (0.45%)  0/223 (0.00%) 
PNEUMOCOCCAL SEPSIS  1  1/224 (0.45%)  0/223 (0.00%) 
PNEUMONIA  1  24/224 (10.71%)  6/223 (2.69%) 
PNEUMONIA PNEUMOCOCCAL  1  1/224 (0.45%)  0/223 (0.00%) 
RESPIRATORY TRACT INFECTION  1  1/224 (0.45%)  0/223 (0.00%) 
SEPSIS  1  1/224 (0.45%)  4/223 (1.79%) 
SEPSIS SYNDROME  1  1/224 (0.45%)  0/223 (0.00%) 
STAPHYLOCOCCAL BACTERAEMIA  1  1/224 (0.45%)  0/223 (0.00%) 
TONSILLITIS  1  0/224 (0.00%)  1/223 (0.45%) 
URINARY TRACT INFECTION  1  3/224 (1.34%)  1/223 (0.45%) 
CLOSTRIDIUM DIFFICILE COLITIS  1  1/224 (0.45%)  0/223 (0.00%) 
INFECTION  1  0/224 (0.00%)  1/223 (0.45%) 
LOBAR PNEUMONIA  1  2/224 (0.89%)  0/223 (0.00%) 
Injury, poisoning and procedural complications     
FALL  1  1/224 (0.45%)  1/223 (0.45%) 
FEMUR FRACTURE  1  1/224 (0.45%)  0/223 (0.00%) 
HEAD INJURY  1  1/224 (0.45%)  0/223 (0.00%) 
HIP FRACTURE  1  1/224 (0.45%)  1/223 (0.45%) 
PELVIC FRACTURE  1  1/224 (0.45%)  0/223 (0.00%) 
POST PROCEDURAL HAEMORRHAGE  1  1/224 (0.45%)  0/223 (0.00%) 
SPINAL COMPRESSION FRACTURE  1  2/224 (0.89%)  0/223 (0.00%) 
VASCULAR PSEUDOANEURYSM  1  1/224 (0.45%)  0/223 (0.00%) 
LUMBAR VERTEBRAL FRACTURE  1  0/224 (0.00%)  1/223 (0.45%) 
SKULL FRACTURE  1  0/224 (0.00%)  1/223 (0.45%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  0/224 (0.00%)  1/223 (0.45%) 
BLOOD BILIRUBIN INCREASED  1  0/224 (0.00%)  1/223 (0.45%) 
BLOOD UREA INCREASED  1  1/224 (0.45%)  0/223 (0.00%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/224 (0.00%)  1/223 (0.45%) 
INTERNATIONAL NORMALISED RATIO INCREASED  1  1/224 (0.45%)  0/223 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION  1  2/224 (0.89%)  3/223 (1.35%) 
DIABETES MELLITUS  1  0/224 (0.00%)  2/223 (0.90%) 
GOUT  1  1/224 (0.45%)  0/223 (0.00%) 
HYPERCALCAEMIA  1  1/224 (0.45%)  1/223 (0.45%) 
HYPERGLYCAEMIA  1  1/224 (0.45%)  1/223 (0.45%) 
HYPOCALCAEMIA  1  1/224 (0.45%)  0/223 (0.00%) 
HYPOGLYCAEMIA  1  1/224 (0.45%)  0/223 (0.00%) 
HYPONATRAEMIA  1  2/224 (0.89%)  3/223 (1.35%) 
TUMOUR LYSIS SYNDROME  1  2/224 (0.89%)  0/223 (0.00%) 
Musculoskeletal and connective tissue disorders     
ARTHROPATHY  1  1/224 (0.45%)  0/223 (0.00%) 
BACK PAIN  1  2/224 (0.89%)  0/223 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION  1  1/224 (0.45%)  0/223 (0.00%) 
MUSCULAR WEAKNESS  1  1/224 (0.45%)  0/223 (0.00%) 
SPINAL OSTEOARTHRITIS  1  1/224 (0.45%)  0/223 (0.00%) 
FLANK PAIN  1  0/224 (0.00%)  1/223 (0.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ADENOCARCINOMA PANCREAS  1  1/224 (0.45%)  0/223 (0.00%) 
BASAL CELL CARCINOMA  1  5/224 (2.23%)  8/223 (3.59%) 
BASOSQUAMOUS CARCINOMA OF SKIN  1  1/224 (0.45%)  1/223 (0.45%) 
BOWEN'S DISEASE  1  0/224 (0.00%)  1/223 (0.45%) 
BREAST CANCER  1  1/224 (0.45%)  0/223 (0.00%) 
CHRONIC LYMPHOCYTIC LEUKAEMIA  1  0/224 (0.00%)  1/223 (0.45%) 
COLON ADENOMA  1  1/224 (0.45%)  0/223 (0.00%) 
HEPATIC CANCER  1  0/224 (0.00%)  1/223 (0.45%) 
HODGKIN'S DISEASE  1  1/224 (0.45%)  0/223 (0.00%) 
LUNG NEOPLASM MALIGNANT  1  1/224 (0.45%)  0/223 (0.00%) 
LUNG SQUAMOUS CELL CARCINOMA STAGE II  1  1/224 (0.45%)  0/223 (0.00%) 
MALIGNANT MELANOMA  1  1/224 (0.45%)  0/223 (0.00%) 
METASTASES TO LIVER  1  1/224 (0.45%)  1/223 (0.45%) 
METASTATIC MALIGNANT MELANOMA  1  0/224 (0.00%)  1/223 (0.45%) 
RICHTER'S SYNDROME  1  0/224 (0.00%)  1/223 (0.45%) 
SKIN CANCER  1  1/224 (0.45%)  1/223 (0.45%) 
SQUAMOUS CELL CARCINOMA  1  1/224 (0.45%)  0/223 (0.00%) 
SQUAMOUS CELL CARCINOMA OF SKIN  1  2/224 (0.89%)  7/223 (3.14%) 
SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY  1  0/224 (0.00%)  1/223 (0.45%) 
TUMOUR FLARE  1  8/224 (3.57%)  0/223 (0.00%) 
Nervous system disorders     
CEREBRAL HAEMORRHAGE  1  0/224 (0.00%)  1/223 (0.45%) 
CEREBRAL INFARCTION  1  1/224 (0.45%)  0/223 (0.00%) 
CEREBRAL ISCHAEMIA  1  0/224 (0.00%)  1/223 (0.45%) 
CEREBROVASCULAR ACCIDENT  1  0/224 (0.00%)  1/223 (0.45%) 
CONVULSION  1  0/224 (0.00%)  1/223 (0.45%) 
HAEMORRHAGE INTRACRANIAL  1  1/224 (0.45%)  0/223 (0.00%) 
HEMIPARESIS  1  0/224 (0.00%)  1/223 (0.45%) 
ISCHAEMIC STROKE  1  0/224 (0.00%)  1/223 (0.45%) 
SCIATICA  1  0/224 (0.00%)  1/223 (0.45%) 
SIMPLE PARTIAL SEIZURES  1  0/224 (0.00%)  1/223 (0.45%) 
SYNCOPE  1  3/224 (1.34%)  0/223 (0.00%) 
TRANSIENT ISCHAEMIC ATTACK  1  3/224 (1.34%)  0/223 (0.00%) 
Psychiatric disorders     
DEPRESSION  1  1/224 (0.45%)  0/223 (0.00%) 
Renal and urinary disorders     
RENAL COLIC  1  1/224 (0.45%)  0/223 (0.00%) 
RENAL FAILURE  1  2/224 (0.89%)  0/223 (0.00%) 
RENAL FAILURE ACUTE  1  3/224 (1.34%)  0/223 (0.00%) 
URINARY RETENTION  1  1/224 (0.45%)  0/223 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
ACUTE PULMONARY OEDEMA  1  0/224 (0.00%)  1/223 (0.45%) 
ACUTE RESPIRATORY FAILURE  1  1/224 (0.45%)  1/223 (0.45%) 
BRONCHIECTASIS  1  0/224 (0.00%)  1/223 (0.45%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  2/224 (0.89%)  1/223 (0.45%) 
DYSPNOEA  1  3/224 (1.34%)  1/223 (0.45%) 
LUNG INFILTRATION  1  0/224 (0.00%)  1/223 (0.45%) 
PLEURAL EFFUSION  1  1/224 (0.45%)  1/223 (0.45%) 
PULMONARY ALVEOLAR HAEMORRHAGE  1  1/224 (0.45%)  0/223 (0.00%) 
PULMONARY EMBOLISM  1  4/224 (1.79%)  1/223 (0.45%) 
PULMONARY HYPERTENSION  1  1/224 (0.45%)  0/223 (0.00%) 
RESPIRATORY FAILURE  1  2/224 (0.89%)  0/223 (0.00%) 
SINUS CONGESTION  1  1/224 (0.45%)  0/223 (0.00%) 
Skin and subcutaneous tissue disorders     
BLISTER  1  0/224 (0.00%)  1/223 (0.45%) 
DRUG ERUPTION  1  1/224 (0.45%)  0/223 (0.00%) 
EXFOLIATIVE RASH  1  2/224 (0.89%)  0/223 (0.00%) 
RASH  1  4/224 (1.79%)  1/223 (0.45%) 
RASH GENERALISED  1  1/224 (0.45%)  0/223 (0.00%) 
RASH MACULO-PAPULAR  1  0/224 (0.00%)  1/223 (0.45%) 
STEVENS-JOHNSON SYNDROME  1  0/224 (0.00%)  1/223 (0.45%) 
URTICARIA  1  1/224 (0.45%)  0/223 (0.00%) 
Vascular disorders     
DEEP VEIN THROMBOSIS  1  3/224 (1.34%)  1/223 (0.45%) 
HYPERTENSIVE CRISIS  1  0/224 (0.00%)  1/223 (0.45%) 
LERICHE SYNDROME  1  1/224 (0.45%)  0/223 (0.00%) 
PERIPHERAL ARTERY ANEURYSM  1  1/224 (0.45%)  0/223 (0.00%) 
SHOCK  1  1/224 (0.45%)  0/223 (0.00%) 
THROMBOPHLEBITIS SUPERFICIAL  1  1/224 (0.45%)  0/223 (0.00%) 
VENOUS THROMBOSIS LIMB  1  1/224 (0.45%)  0/223 (0.00%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lenalidomide Chlorambucil
Affected / at Risk (%) Affected / at Risk (%)
Total   204/224 (91.07%)   184/223 (82.51%) 
Blood and lymphatic system disorders     
NEUTROPENIA  1  126/224 (56.25%)  74/223 (33.18%) 
ANAEMIA  1  69/224 (30.80%)  46/223 (20.63%) 
THROMBOCYTOPENIA  1  72/224 (32.14%)  50/223 (22.42%) 
Gastrointestinal disorders     
VOMITING  1  11/224 (4.91%)  28/223 (12.56%) 
ABDOMINAL PAIN  1  30/224 (13.39%)  10/223 (4.48%) 
CONSTIPATION  1  28/224 (12.50%)  17/223 (7.62%) 
DIARRHOEA  1  66/224 (29.46%)  32/223 (14.35%) 
NAUSEA  1  33/224 (14.73%)  63/223 (28.25%) 
General disorders     
ASTHENIA  1  19/224 (8.48%)  10/223 (4.48%) 
PYREXIA  1  37/224 (16.52%)  18/223 (8.07%) 
FATIGUE  1  66/224 (29.46%)  53/223 (23.77%) 
OEDEMA PERIPHERAL  1  43/224 (19.20%)  16/223 (7.17%) 
Infections and infestations     
NASOPHARYNGITIS  1  12/224 (5.36%)  3/223 (1.35%) 
PNEUMONIA  1  13/224 (5.80%)  1/223 (0.45%) 
BRONCHITIS  1  16/224 (7.14%)  4/223 (1.79%) 
INFLUENZA  1  13/224 (5.80%)  2/223 (0.90%) 
UPPER RESPIRATORY TRACT INFECTION  1  16/224 (7.14%)  11/223 (4.93%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  14/224 (6.25%)  7/223 (3.14%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  14/224 (6.25%)  7/223 (3.14%) 
BLOOD CREATININE INCREASED  1  22/224 (9.82%)  7/223 (3.14%) 
WEIGHT DECREASED  1  34/224 (15.18%)  23/223 (10.31%) 
Metabolism and nutrition disorders     
DECREASED APPETITE  1  30/224 (13.39%)  13/223 (5.83%) 
HYPERKALAEMIA  1  12/224 (5.36%)  4/223 (1.79%) 
Musculoskeletal and connective tissue disorders     
PAIN IN EXTREMITY  1  16/224 (7.14%)  4/223 (1.79%) 
ARTHRALGIA  1  15/224 (6.70%)  12/223 (5.38%) 
BACK PAIN  1  28/224 (12.50%)  18/223 (8.07%) 
MUSCLE SPASMS  1  15/224 (6.70%)  5/223 (2.24%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
TUMOUR FLARE  1  85/224 (37.95%)  11/223 (4.93%) 
Nervous system disorders     
DIZZINESS  1  16/224 (7.14%)  12/223 (5.38%) 
HEADACHE  1  16/224 (7.14%)  11/223 (4.93%) 
Psychiatric disorders     
INSOMNIA  1  14/224 (6.25%)  11/223 (4.93%) 
Respiratory, thoracic and mediastinal disorders     
DYSPNOEA  1  21/224 (9.38%)  12/223 (5.38%) 
COUGH  1  38/224 (16.96%)  21/223 (9.42%) 
Skin and subcutaneous tissue disorders     
NIGHT SWEATS  1  24/224 (10.71%)  14/223 (6.28%) 
PRURITUS  1  18/224 (8.04%)  7/223 (3.14%) 
RASH  1  41/224 (18.30%)  19/223 (8.52%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
After notification by the US Food and Drug Administration on 12Jul2013, Celgene agreed to stop lenalidomide due to an imbalance in the number of deaths on the lenalidomide arm versus the chlorambucil arm; no causality for the imbalance was identified
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 12 months since study completion. Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager of Clinical Trial Disclosure
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: ClinicalTrialDisclosure@Celgene.com
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00910910     History of Changes
Other Study ID Numbers: CC-5013-CLL-008
2008-003079-32 ( EudraCT Number )
First Submitted: May 28, 2009
First Posted: June 1, 2009
Results First Submitted: September 23, 2015
Results First Posted: December 21, 2016
Last Update Posted: July 9, 2019