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A Study to Assess the Effect of Maintenance Treatment With Rituximab Versus No Treatment in Participants With Progressive B-Cell Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT00718549
Recruitment Status : Completed
First Posted : July 18, 2008
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphocytic Leukemia, Chronic
Interventions Drug: Cladribine
Drug: Cyclophosphamide
Drug: Rituximab
Enrollment 128
Recruitment Details  
Pre-assignment Details A total 136 participants were screened, out of which 128 participants were enrolled in this study.
Arm/Group Title Induction: Rituximab, Cladribine, Cyclophosphamide Maintenance Arm: Rituximab Observation Arm: No Intervention
Hide Arm/Group Description Participants received rituximab at a dose of 375 milligrams per meter squared (mg/m^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 minutes (min) on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration. Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks). Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Period Title: Induction Phase
Started 128 0 0
Completed 66 0 0
Not Completed 62 0 0
Reason Not Completed
Disease Progression             1             0             0
Eligibility Criteria Violation             2             0             0
Early Termination - No Additional Info             59             0             0
Period Title: Maintenance/ Observation Phase
Started 0 33 33
Completed 0 5 3
Not Completed 0 28 30
Reason Not Completed
Early Termination - No Additional Info             0             15             8
Death             0             1             2
Lost to Follow-up             0             4             4
Progression             0             5             14
Relapse             0             3             2
Arm/Group Title Induction: Rituximab, Cladribine, Cyclophosphamide
Hide Arm/Group Description Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.
Overall Number of Baseline Participants 128
Hide Baseline Analysis Population Description
All enrolled participants who received at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 128 participants
57.5  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 128 participants
Female
44
  34.4%
Male
84
  65.6%
1.Primary Outcome
Title Percentage of Participants With Disease Progression (PD), Relapse, or Death Due to Any Cause Assessed According to the National Cancer Institute (NCI) Revised Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia (CLL)
Hide Description PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (greater than [>]1.5 centimeters [cm]), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of greater than or equal to (>/=) 50 percent (%) in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by >/=50%; an increase in the number of blood lymphocytes by >/=50% with B-lymphocytes >/=5000 per microliter (/mcL); transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Time Frame From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least one dose of study medication and had at least one post-treatment efficacy measurement available. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title Maintenance Arm: Rituximab Observation Arm: No Intervention All Randomized Participants
Hide Arm/Group Description:
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 33 33 66
Measure Type: Number
Unit of Measure: percentage of participants
27.3 54.5 40.9
2.Primary Outcome
Title Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
Hide Description PFS was defined as the time from date of randomization to date of PD, relapse, or death due to any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD occurred if any of the following events was observed: appearance of any new lesion, such as enlarged lymph nodes (>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of >/=50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by >/=50%; an increase in the number of blood lymphocytes by >/=50% with B-lymphocytes >/=5000/mcL; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL.
Time Frame From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title Maintenance Arm: Rituximab Observation Arm: No Intervention All Randomized Participants
Hide Arm/Group Description:
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 33 33 66
Median (95% Confidence Interval)
Unit of Measure: years
NA [1] 
(3.0 to NA)
2.1 [2] 
(1.9 to NA)
3.1 [2] 
(2.2 to NA)
[1]
Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.
[2]
Upper Limit could not be calculated due to insufficient number of participants who had an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance Arm: Rituximab, Observation Arm: No Intervention
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance Arm: Rituximab, Observation Arm: No Intervention
Comments Univariate comparison
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Cox's proportional hazards regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.418
Confidence Interval 95%
0.187 to 0.933
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maintenance Arm: Rituximab, Observation Arm: No Intervention
Comments Multivariate Comparison
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.052
Confidence Interval (2-Sided) 95%
0.001 to 1.972
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
Hide Description CR was achieved if participants met all of the following criteria >/= 2 months after last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, platelets (PL) >100,000/mcL, hemoglobin (Hb) >11.0 grams per deciliter (g/dL), bone marrow (BM) sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly (decrease in lymph node size by >/=50% compared to pre-treatment state, no increase in any lymph node, no new enlarged lymph node); a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline).
Time Frame 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Maintenance Arm: Rituximab Observation Arm: No Intervention Overall Population
Hide Arm/Group Description:
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 21 18 97
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 29 Number Analyzed 0 participants 0 participants 97 participants
73.2
(64.9 to 82.1)
Week 129 Number Analyzed 21 participants 18 participants 39 participants
90.5
(85.7 to 100.0)
72.2
(55.6 to 92.9)
82.1
(71.8 to 93.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance Arm: Rituximab, Observation Arm: No Intervention
Comments Week 129: Univariate Comparison
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.155
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.654
Confidence Interval (2-Sided) 95%
0.674 to 28.337
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR
Hide Description MRD was defined by the presence of tumor cells in bone marrow, using 4-color flow cytometry of cluster of differentiation (CD)19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR: if participants met all of the following criteria >/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, PL >100,000/mcL, Hb >11.0 g/dL, BM sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly; a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline).
Time Frame 8 weeks after the last dose of rituximab during induction treatment (Week 29) and 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
Arm/Group Title Maintenance Arm: Rituximab Observation Arm: No Intervention All Randomized Participants
Hide Arm/Group Description:
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 14 10 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 29 Number Analyzed 0 participants 0 participants 65 participants
15.4
(7.7 to 23.7)
Week 129 Number Analyzed 14 participants 10 participants 24 participants
28.6
(14.3 to 55.6)
20.0
(10.0 to 48.7)
25.0
(12.5 to 43.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance Arm: Rituximab, Observation Arm: No Intervention
Comments Week 129: Univariate comparison
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.634
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.625
Confidence Interval (2-Sided) 95%
0.073 to 4.114
Estimation Comments [Not Specified]
5.Secondary Outcome
Title PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors
Hide Description PFS: time from date of randomization to date of PD, relapse, or death from any cause. Participants alive with no evidence of PD or relapse were censored at date of last clinical examination. PD: appearance of any new lesion, such as enlarged lymph nodes (>1.5 cm), splenomegaly, hepatomegaly, or other organ infiltrates; an increase of >/=50% in greatest determined diameter of any previous site; an increase in previously noted enlargement of liver or spleen by >/=50%; an increase in number of blood lymphocytes by >/=50% with B-lymphocytes >/=5000/mcL; transformation to a more aggressive histology; or occurrence of cytopenia attributable to CLL. Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and clinical outcome (PFS) after study treatment.
Time Frame From randomization to PD, relapse, or death due to any cause (overall approximately 5 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Overall Number of Participants Analyzed: participants evaluable for this outcome; Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among All Randomized Participants only.
Arm/Group Title All Randomized Participants
Hide Arm/Group Description:
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 66
Median (95% Confidence Interval)
Unit of Measure: years
Age <60 years Number Analyzed 41 participants
3.0 [1] 
(2.2 to NA)
Age >/=60 years Number Analyzed 25 participants
4.0 [1] 
(1.9 to NA)
Sex: Female Number Analyzed 24 participants
4.0 [1] 
(2.2 to NA)
Sex: Male Number Analyzed 42 participants
3.0 [1] 
(2.1 to NA)
Rai Stage: I or II Number Analyzed 52 participants
3.1 [1] 
(2.1 to NA)
Rai Stage: III or IV Number Analyzed 14 participants
3.0 [1] 
(2.1 to NA)
Beta-2-Microglobulin >/= Median Value Number Analyzed 27 participants
1.9 [1] 
(1.4 to NA)
Beta-2-Microglobulin <Median Value Number Analyzed 38 participants
NA [2] 
(3.5 to NA)
Zeta-Associated Protein (ZAP)-70: Negative Number Analyzed 45 participants
3.0 [1] 
(2.1 to NA)
ZAP-70 Expression: Positive Number Analyzed 15 participants
NA [2] 
(4.0 to NA)
CD38 Expression: Negative Number Analyzed 18 participants
2.1 [1] 
(1.9 to NA)
CD38 Expression: Positive Number Analyzed 23 participants
2.8 [1] 
(1.9 to NA)
Cytogenetic abnormality 17p: No Number Analyzed 54 participants
3.1 [1] 
(2.2 to NA)
Cytogenetic abnormality 17p: Yes Number Analyzed 5 participants
1.9 [1] 
(1.9 to NA)
Cytogenetic abnormality 13q: No Number Analyzed 21 participants
3.5 [1] 
(1.4 to NA)
Cytogenetic abnormality 13q: Yes Number Analyzed 31 participants
3.0 [1] 
(1.9 to NA)
Cytogenetic abnormality 11q: No Number Analyzed 37 participants
3.5 [1] 
(2.1 to NA)
Cytogenetic abnormality 11q: Yes Number Analyzed 18 participants
2.8 [1] 
(1.9 to NA)
Cytogenetic abnormality 12q: No Number Analyzed 41 participants
2.2 [1] 
(1.9 to NA)
Cytogenetic abnormality 12q: Yes Number Analyzed 4 participants
3.1 [1] 
(3.1 to NA)
[1]
Upper Limit could not be calculated due to insufficient number of participants who had an event.
[2]
Median and Upper Limit could not be calculated due to insufficient number of participants who had an event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Age <60 years versus Age >/=60 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.752
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.769
Confidence Interval (2-Sided) 95%
0.151 to 3.920
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Sex: Female versus Male
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.068
Confidence Interval (2-Sided) 95%
0.002 to 2.158
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.728
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.282
Confidence Interval (2-Sided) 95%
0.022 to 240.864
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Beta-2-Microglobulin >/= Median Value versus Beta-2-Microglobulin <Median Value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 26.275
Confidence Interval (2-Sided) 95%
1.036 to 666.708
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: ZAP-70 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.417
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.210
Confidence Interval (2-Sided) 95%
0.005 to 9.100
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: CD38 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.197
Confidence Interval (2-Sided) 95%
0.024 to 1.647
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Cytogenetic abnormality 17p No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 8.373
Confidence Interval (2-Sided) 95%
0.045 to 1568.717
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Cytogenetic abnormality 13q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.733
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.438
Confidence Interval (2-Sided) 95%
0.004 to 50.334
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Cytogenetic abnormality 11q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.463
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.621
Confidence Interval (2-Sided) 95%
0.200 to 34.422
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Multivariate Comparison: Cytogenetic abnormality 12q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.397
Comments [Not Specified]
Method Cox’s proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.288
Confidence Interval (2-Sided) 95%
0.016 to 5.122
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 29
Hide Description CR was achieved if participants met all of the following criteria >/= 2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, PL >100,000/mcL, Hb >11.0 g/dL, BM sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly; a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
Time Frame 8 weeks after the last dose of rituximab during induction treatment (Week 29)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among Participants included in Overall IIT population only.
Arm/Group Title Overall Population
Hide Arm/Group Description:
Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 97
Measure Type: Number
Unit of Measure: percentage of participants
Age <60 years Number Analyzed 60 participants
73.3
Age >/=60 years Number Analyzed 37 participants
73.0
Sex: Female Number Analyzed 31 participants
80.6
Sex: Male Number Analyzed 66 participants
69.7
Rai Stage: I or II Number Analyzed 71 participants
77.5
Rai Stage: III or IV Number Analyzed 26 participants
61.5
Beta-2-Microglobulin >/= Median Value Number Analyzed 48 participants
64.6
Beta-2-Microglobulin <Median Value Number Analyzed 47 participants
83.0
ZAP-70 Expression: Negative Number Analyzed 70 participants
67.1
ZAP-70 Expression: Positive Number Analyzed 19 participants
94.7
CD38 Expression: Negative Number Analyzed 26 participants
73.1
CD38 Expression: Positive Number Analyzed 35 participants
71.4
Cytogenetic abnormality 17p: No Number Analyzed 81 participants
72.8
Cytogenetic abnormality 17p: Yes Number Analyzed 7 participants
71.4
Cytogenetic abnormality 13q: No Number Analyzed 35 participants
62.9
Cytogenetic abnormality 13q: Yes Number Analyzed 46 participants
76.1
Cytogenetic abnormality 11q: No Number Analyzed 59 participants
69.5
Cytogenetic abnormality 11q: Yes Number Analyzed 24 participants
79.2
Cytogenetic abnormality 12q: No Number Analyzed 68 participants
67.6
Cytogenetic abnormality 12q: Yes Number Analyzed 6 participants
66.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Age <60 years versus Age >/=60 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.969
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.982
Confidence Interval (2-Sided) 95%
0.393 to 2.531
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Sex: Female versus Male
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.260
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.552
Confidence Interval (2-Sided) 95%
0.183 to 1.488
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.465
Confidence Interval (2-Sided) 95%
0.177 to 1.242
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Beta-2-Microglobulin >/= Median Value versus Beta-2-Microglobulin <Median Value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.374
Confidence Interval (2-Sided) 95%
0.137 to 0.957
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: ZAP-70 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.809
Confidence Interval (2-Sided) 95%
1.655 to 163.316
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: CD38 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.887
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.921
Confidence Interval (2-Sided) 95%
0.287 to 2.851
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Cytogenetic abnormality 17p No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.936
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.932
Confidence Interval (2-Sided) 95%
0.186 to 6.839
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Cytogenetic abnormality 13q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.880
Confidence Interval (2-Sided) 95%
0.719 to 5.012
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Cytogenetic abnormality 11q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.375
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.668
Confidence Interval (2-Sided) 95%
0.566 to 5.649
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Overall Population
Comments Univariate Comparison: Cytogenetic abnormality 12q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.961
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.957
Confidence Interval (2-Sided) 95%
0.173 to 7.275
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors at Week 129
Hide Description CR was achieved if participants met all of the following criteria >/=2 months after last treatment: no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, PL >100,000/mcL, Hb >11.0 g/dL, BM sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly; a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed the relationship between clinical markers and clinical outcome (response) after study treatment.
Time Frame 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Overall Number of Participants Analyzed: participants evaluable for this outcome; Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among All Randomized Participants only.
Arm/Group Title All Randomized Participants
Hide Arm/Group Description:
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 39
Measure Type: Number
Unit of Measure: percentage of participants
Age <60 years Number Analyzed 26 participants
80.8
Age >/=60 years Number Analyzed 13 participants
84.6
Sex: Female Number Analyzed 14 participants
85.7
Sex: Male Number Analyzed 25 participants
80.0
Rai Stage: I or II Number Analyzed 31 participants
80.6
Rai Stage: III or IV Number Analyzed 8 participants
87.5
Beta-2-Microglobulin >/= Median Value Number Analyzed 13 participants
76.9
Beta-2-Microglobulin <Median Value Number Analyzed 25 participants
84.0
ZAP-70 Expression: Negative Number Analyzed 24 participants
83.3
ZAP-70 Expression: Positive Number Analyzed 12 participants
83.3
CD38 Expression: Negative Number Analyzed 9 participants
77.8
CD38 Expression: Positive Number Analyzed 12 participants
75.0
Cytogenetic abnormality 17p: No Number Analyzed 30 participants
86.7
Cytogenetic abnormality 17p: Yes Number Analyzed 2 participants
50.0
Cytogenetic abnormality 13q: No Number Analyzed 10 participants
90.0
Cytogenetic abnormality 13q: Yes Number Analyzed 17 participants
76.5
Cytogenetic abnormality 11q: No Number Analyzed 19 participants
84.2
Cytogenetic abnormality 11q: Yes Number Analyzed 10 participants
80.0
Cytogenetic abnormality 12q: No Number Analyzed 21 participants
76.2
Cytogenetic abnormality 12q: Yes Number Analyzed 3 participants
100.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Age <60 years versus Age >/=60 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.768
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.310
Confidence Interval (2-Sided) 95%
0.237 to 10.189
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Sex: Female versus Male
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.657
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.667
Confidence Interval (2-Sided) 95%
0.086 to 3.653
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.655
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.680
Confidence Interval (2-Sided) 95%
0.229 to 34.486
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Beta-2-Microglobulin >/= Median Value versus Beta-2-Microglobulin <Median Value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.595
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.635
Confidence Interval (2-Sided) 95%
0.117 to 3.730
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: ZAP-70 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.000
Confidence Interval (2-Sided) 95%
0.164 to 8.102
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: CD38 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.882
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.857
Confidence Interval (2-Sided) 95%
0.093 to 6.636
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 17p No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.216
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.154
Confidence Interval (2-Sided) 95%
0.005 to 4.405
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 13q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.396
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.361
Confidence Interval (2-Sided) 95%
0.017 to 2.971
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 11q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.776
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.750
Confidence Interval (2-Sided) 95%
0.103 to 6.572
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29
Hide Description MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, PL >100,000/mcL, Hb >11.0 g/dL, BM sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly; a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
Time Frame 8 weeks after the last dose of rituximab during induction treatment (Week 29)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Overall Number of Participants Analyzed: participants evaluable for this outcome; Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among All Randomized Participants only.
Arm/Group Title All Randomized Participants
Hide Arm/Group Description:
Participants with PR or CR after induction phase were randomized to either observation arm (received no intervention) or to maintenance arm (received maintenance treatment with rituximab administered at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles until disease progression for up to approximately 96 weeks).
Overall Number of Participants Analyzed 65
Measure Type: Number
Unit of Measure: percentage of participants
Age <60 years Number Analyzed 41 participants
87.8
Age >/=60 years Number Analyzed 24 participants
79.2
Sex: Female Number Analyzed 24 participants
87.5
Sex: Male Number Analyzed 41 participants
82.9
Rai Stage: I or II Number Analyzed 51 participants
80.4
Rai Stage: III or IV Number Analyzed 14 participants
100.0
Beta-2-Microglobulin >/= Median Value Number Analyzed 29 participants
93.1
Beta-2-Microglobulin <Median Value Number Analyzed 35 participants
77.1
ZAP-70 Expression: Negative Number Analyzed 46 participants
82.6
ZAP-70 Expression: Positive Number Analyzed 15 participants
100.0
CD38 Expression: Negative Number Analyzed 18 participants
83.3
CD38 Expression: Positive Number Analyzed 22 participants
95.5
Cytogenetic abnormality 17p: No Number Analyzed 55 participants
83.6
Cytogenetic abnormality 17p: Yes Number Analyzed 4 participants
100.0
Cytogenetic abnormality 13q: No Number Analyzed 19 participants
84.2
Cytogenetic abnormality 13q: Yes Number Analyzed 33 participants
81.8
Cytogenetic abnormality 11q: No Number Analyzed 36 participants
83.3
Cytogenetic abnormality 11q: Yes Number Analyzed 19 participants
84.2
Cytogenetic abnormality 12q: No Number Analyzed 41 participants
80.5
Cytogenetic abnormality 12q: Yes Number Analyzed 4 participants
75.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Age <60 years versus Age >/=60 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.357
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.528
Confidence Interval (2-Sided) 95%
0.131 to 2.114
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Sex: Female versus Male
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.623
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.694
Confidence Interval (2-Sided) 95%
0.138 to 2.800
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Beta-2-Microglobulin >/= Median Value versus Beta-2-Microglobulin <Median Value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.097
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.000
Confidence Interval (2-Sided) 95%
0.901 to 28.158
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: CD38 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.233
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.200
Confidence Interval (2-Sided) 95%
0.484 to 89.588
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 13q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.826
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.844
Confidence Interval (2-Sided) 95%
0.161 to 3.681
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 11q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.933
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.067
Confidence Interval (2-Sided) 95%
0.246 to 5.581
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 12q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.794
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.727
Confidence Interval (2-Sided) 95%
0.080 to 15.779
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129
Hide Description MRD: the presence of tumor cells in bone marrow, using 4-color flow cytometry of CD19/CD5/CD20/CD79b. MRD was assessed in participants who achieved CR or PR. CR (>/=2 months after last treatment): no Ly/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils >1500/mcL, PL >100,000/mcL, Hb >11.0 g/dL, BM sample must be normocellular for age with lymphocytes <30% of nucleated cells. PR: a reduction in Ly; a reduction of >/=50% from pre-treatment state in the lymphocytes count, and in enlargement of the spleen or liver; any one of the following: neutrophils >1500/mcL, PL >100,000/mcL (or 50% improvement from baseline), Hb >11.0 g/dL (or 50% improvement from baseline). Rai Stage: staging for CLL, based on lymphocyte, red blood cell and platelet counts and size of lymph nodes, spleen, and liver. Rai Stage I or II are intermediate risk CLL and Rai Stage III or IV are high risk CLL. This outcome measure assessed relationship between clinical markers and MRD after study treatment.
Time Frame 12 weeks after the end of maintenance treatment or observation phase (Week 129)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Overall Number of Participants Analyzed: participants evaluable for this outcome; Number Analyzed: participants evaluable for specified category. This outcome was planned to be reported for groups defined by clinical and biochemical factors (i.e. reported categories) among All Randomized Participants only.
Arm/Group Title All Randomized Participants
Hide Arm/Group Description:
Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression [up to approximately 96 weeks]).
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
Age <60 years Number Analyzed 18 participants
72.2
Age >/=60 years Number Analyzed 6 participants
83.3
Sex: Female Number Analyzed 7 participants
71.4
Sex: Male Number Analyzed 17 participants
76.5
Rai Stage: I or II Number Analyzed 20 participants
75.0
Rai Stage: III or IV Number Analyzed 4 participants
75.0
Beta-2-Microglobulin >/= Median Value Number Analyzed 9 participants
88.9
Beta-2-Microglobulin <Median Value Number Analyzed 14 participants
71.4
ZAP-70 Expression: Negative Number Analyzed 15 participants
66.7
ZAP-70 Expression: Positive Number Analyzed 7 participants
100.0
CD38 Expression: Negative Number Analyzed 5 participants
60.0
CD38 Expression: Positive Number Analyzed 9 participants
77.8
Cytogenetic abnormality 17p: No Number Analyzed 21 participants
76.2
Cytogenetic abnormality 17p: Yes Number Analyzed 1 participants
0.0
Cytogenetic abnormality 13q: No Number Analyzed 8 participants
75.0
Cytogenetic abnormality 13q: Yes Number Analyzed 12 participants
66.7
Cytogenetic abnormality 11q: No Number Analyzed 12 participants
66.7
Cytogenetic abnormality 11q: Yes Number Analyzed 8 participants
75.0
Cytogenetic abnormality 12q: No Number Analyzed 15 participants
66.7
Cytogenetic abnormality 12q: Yes Number Analyzed 3 participants
66.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Age <60 years versus Age >/=60 years
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.591
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.923
Confidence Interval (2-Sided) 95%
0.225 to 41.751
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Sex: Female versus Male
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.796
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.300
Confidence Interval (2-Sided) 95%
0.147 to 9.222
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Beta-2-Microglobulin >/= Median Value versus Beta-2-Microglobulin <Median Value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.338
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.200
Confidence Interval (2-Sided) 95%
0.375 to 69.479
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: CD38 Expression Negative versus Positive
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.486
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.333
Confidence Interval (2-Sided) 95%
0.201 to 29.008
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 13q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.691
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.667
Confidence Interval (2-Sided) 95%
0.074 to 4.722
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 11q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.691
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.500
Confidence Interval (2-Sided) 95%
0.212 to 13.563
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Cytogenetic abnormality 12q No versus Yes
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.000
Confidence Interval (2-Sided) 95%
0.076 to 24.621
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection All Randomized Participants
Comments Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.000
Confidence Interval (2-Sided) 95%
0.099 to 22.791
Estimation Comments [Not Specified]
Time Frame From Day 1 to end of study (up to 261 weeks)
Adverse Event Reporting Description All enrolled participants who received at least one dose of study medication were included in the analysis.
 
Arm/Group Title Induction (Excluding Maintenance/ Observation) Maintenance Arm: Rituximab Observation Arm: No Intervention All Participants
Hide Arm/Group Description Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration. Only participants who were not randomized to maintenance or observation arm were included. Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks). Participants received rituximab at a dose of 375 mg/m^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks. All enrolled participants who received at least one dose of study medication were included in the analysis.
All-Cause Mortality
Induction (Excluding Maintenance/ Observation) Maintenance Arm: Rituximab Observation Arm: No Intervention All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Induction (Excluding Maintenance/ Observation) Maintenance Arm: Rituximab Observation Arm: No Intervention All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/62 (37.10%)   13/33 (39.39%)   9/33 (27.27%)   45/128 (35.16%) 
Blood and lymphatic system disorders         
Anaemia * 1  2/62 (3.23%)  0/33 (0.00%)  0/33 (0.00%)  2/128 (1.56%) 
Aplasia pure red cell * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Febrile neutropenia * 1  4/62 (6.45%)  2/33 (6.06%)  0/33 (0.00%)  6/128 (4.69%) 
Leukopenia * 1  0/62 (0.00%)  1/33 (3.03%)  2/33 (6.06%)  3/128 (2.34%) 
Neutropenia * 1  1/62 (1.61%)  4/33 (12.12%)  0/33 (0.00%)  5/128 (3.91%) 
Pancytopenia * 1  3/62 (4.84%)  0/33 (0.00%)  0/33 (0.00%)  3/128 (2.34%) 
Thrombocytopenia * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Cardiac disorders         
Atrial fibrillation * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Gastrointestinal disorders         
Abdominal pain upper * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Diarrhoea * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
General disorders         
Disease progression * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Pelvic mass * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Pyrexia * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Soft tissue inflammation * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Hepatobiliary disorders         
Cholecystitis acute * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Infections and infestations         
Appendiceal abscess * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Bacterial sepsis * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Cytomegalovirus infection * 1  2/62 (3.23%)  0/33 (0.00%)  0/33 (0.00%)  2/128 (1.56%) 
Herpes zoster * 1  2/62 (3.23%)  0/33 (0.00%)  1/33 (3.03%)  3/128 (2.34%) 
Oral fungal infection * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Pneumonia * 1  1/62 (1.61%)  1/33 (3.03%)  2/33 (6.06%)  4/128 (3.13%) 
Injury, poisoning and procedural complications         
Overdose * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Metabolism and nutrition disorders         
Abnormal loss of weight * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Musculoskeletal and connective tissue disorders         
Groin abscess * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Myositis * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Sympathetic posterior cervical syndrome * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute leukaemia * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Breast cancer recurrent * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Lip neoplasm malignant stage unspecified * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Meningioma * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Richter's syndrome * 1  1/62 (1.61%)  0/33 (0.00%)  1/33 (3.03%)  2/128 (1.56%) 
Squamous cell carcinoma of skin * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Uterine cancer * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Nervous system disorders         
Haemorrhage intracranial * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Loss of consciousness * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Renal and urinary disorders         
Renal failure * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Reproductive system and breast disorders         
Endometrial hyperplasia * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Uterine polyp * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Respiratory, thoracic and mediastinal disorders         
Bronchitis * 1  1/62 (1.61%)  0/33 (0.00%)  1/33 (3.03%)  2/128 (1.56%) 
Pulmonary embolism * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Skin and subcutaneous tissue disorders         
Acne varioliformis * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Cellulitis * 1  1/62 (1.61%)  0/33 (0.00%)  0/33 (0.00%)  1/128 (0.78%) 
Skin ulcer * 1  0/62 (0.00%)  1/33 (3.03%)  0/33 (0.00%)  1/128 (0.78%) 
Toxic epidermal necrolysis * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
Surgical and medical procedures         
Heart valve operation * 1  0/62 (0.00%)  0/33 (0.00%)  1/33 (3.03%)  1/128 (0.78%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction (Excluding Maintenance/ Observation) Maintenance Arm: Rituximab Observation Arm: No Intervention All Participants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   58/62 (93.55%)   31/33 (93.94%)   32/33 (96.97%)   121/128 (94.53%) 
Blood and lymphatic system disorders         
Anaemia * 1  11/62 (17.74%)  1/33 (3.03%)  3/33 (9.09%)  15/128 (11.72%) 
Leukopenia * 1  1/62 (1.61%)  6/33 (18.18%)  6/33 (18.18%)  13/128 (10.16%) 
Lymphopenia * 1  0/62 (0.00%)  3/33 (9.09%)  5/33 (15.15%)  8/128 (6.25%) 
Neutropenia * 1  47/62 (75.81%)  26/33 (78.79%)  20/33 (60.61%)  93/128 (72.66%) 
Thrombocytopenia * 1  18/62 (29.03%)  5/33 (15.15%)  5/33 (15.15%)  28/128 (21.88%) 
Cardiac disorders         
Cardiomegaly * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Endocrine disorders         
Goitre * 1  0/62 (0.00%)  1/33 (3.03%)  2/33 (6.06%)  3/128 (2.34%) 
Gastrointestinal disorders         
Abdominal pain * 1  2/62 (3.23%)  0/33 (0.00%)  2/33 (6.06%)  4/128 (3.13%) 
Abdominal pain upper * 1  0/62 (0.00%)  1/33 (3.03%)  2/33 (6.06%)  3/128 (2.34%) 
Diarrhoea * 1  6/62 (9.68%)  7/33 (21.21%)  3/33 (9.09%)  16/128 (12.50%) 
Nausea * 1  7/62 (11.29%)  12/33 (36.36%)  4/33 (12.12%)  23/128 (17.97%) 
Vomiting * 1  4/62 (6.45%)  0/33 (0.00%)  1/33 (3.03%)  5/128 (3.91%) 
General disorders         
Asthenia * 1  3/62 (4.84%)  2/33 (6.06%)  2/33 (6.06%)  7/128 (5.47%) 
Chills * 1  8/62 (12.90%)  3/33 (9.09%)  3/33 (9.09%)  14/128 (10.94%) 
Influenza like illness * 1  0/62 (0.00%)  0/33 (0.00%)  2/33 (6.06%)  2/128 (1.56%) 
Pyrexia * 1  11/62 (17.74%)  5/33 (15.15%)  3/33 (9.09%)  19/128 (14.84%) 
Hepatobiliary disorders         
Hepatomegaly * 1  0/62 (0.00%)  0/33 (0.00%)  3/33 (9.09%)  3/128 (2.34%) 
Hepatic steatosis * 1  0/62 (0.00%)  2/33 (6.06%)  2/33 (6.06%)  4/128 (3.13%) 
Infections and infestations         
Chronic sinusitis * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Oral herpes * 1  2/62 (3.23%)  1/33 (3.03%)  2/33 (6.06%)  5/128 (3.91%) 
Respiratory tract infection * 1  1/62 (1.61%)  2/33 (6.06%)  2/33 (6.06%)  5/128 (3.91%) 
Upper respiratory tract infection * 1  4/62 (6.45%)  3/33 (9.09%)  6/33 (18.18%)  13/128 (10.16%) 
Urinary tract infection * 1  0/62 (0.00%)  3/33 (9.09%)  1/33 (3.03%)  4/128 (3.13%) 
Investigations         
Blood lactate dehydrogenase increased * 1  1/62 (1.61%)  0/33 (0.00%)  2/33 (6.06%)  3/128 (2.34%) 
Hepatic enzyme increased * 1  0/62 (0.00%)  2/33 (6.06%)  2/33 (6.06%)  4/128 (3.13%) 
Metabolism and nutrition disorders         
Diabetes mellitus * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Hyperuricaemia * 1  5/62 (8.06%)  4/33 (12.12%)  2/33 (6.06%)  11/128 (8.59%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Back pain * 1  0/62 (0.00%)  2/33 (6.06%)  2/33 (6.06%)  4/128 (3.13%) 
Osteoarthritis * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Haemangioma of liver * 1  0/62 (0.00%)  2/33 (6.06%)  1/33 (3.03%)  3/128 (2.34%) 
Metastasis * 1  0/62 (0.00%)  3/33 (9.09%)  3/33 (9.09%)  6/128 (4.69%) 
Nervous system disorders         
Headache * 1  2/62 (3.23%)  2/33 (6.06%)  2/33 (6.06%)  6/128 (4.69%) 
Sciatica * 1  1/62 (1.61%)  2/33 (6.06%)  1/33 (3.03%)  4/128 (3.13%) 
Renal and urinary disorders         
Nephroptosis * 1  0/62 (0.00%)  0/33 (0.00%)  3/33 (9.09%)  3/128 (2.34%) 
Renal cyst * 1  0/62 (0.00%)  2/33 (6.06%)  5/33 (15.15%)  7/128 (5.47%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia * 1  0/62 (0.00%)  2/33 (6.06%)  0/33 (0.00%)  2/128 (1.56%) 
Respiratory, thoracic and mediastinal disorders         
Bronchitis * 1  2/62 (3.23%)  3/33 (9.09%)  1/33 (3.03%)  6/128 (4.69%) 
Cough * 1  2/62 (3.23%)  4/33 (12.12%)  0/33 (0.00%)  6/128 (4.69%) 
Emphysema * 1  0/62 (0.00%)  3/33 (9.09%)  4/33 (12.12%)  7/128 (5.47%) 
Oropharyngeal pain * 1  1/62 (1.61%)  2/33 (6.06%)  1/33 (3.03%)  4/128 (3.13%) 
Pulmonary fibrosis * 1  0/62 (0.00%)  6/33 (18.18%)  2/33 (6.06%)  8/128 (6.25%) 
Skin and subcutaneous tissue disorders         
Pruritus * 1  0/62 (0.00%)  3/33 (9.09%)  1/33 (3.03%)  4/128 (3.13%) 
Rash * 1  1/62 (1.61%)  2/33 (6.06%)  1/33 (3.03%)  4/128 (3.13%) 
Rash pruritic * 1  4/62 (6.45%)  1/33 (3.03%)  1/33 (3.03%)  6/128 (4.69%) 
Vascular disorders         
Aortic arteriosclerosis * 1  0/62 (0.00%)  1/33 (3.03%)  2/33 (6.06%)  3/128 (2.34%) 
Hypertension * 1  2/62 (3.23%)  4/33 (12.12%)  3/33 (9.09%)  9/128 (7.03%) 
Hypotension * 1  3/62 (4.84%)  0/33 (0.00%)  2/33 (6.06%)  5/128 (3.91%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA v19.0
In 2011 the recruitment was stopped due to low enrollment rate, and in 2015 the trial was prematurely discontinued.
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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00718549     History of Changes
Other Study ID Numbers: ML21283
2008-001140-39
First Submitted: July 16, 2008
First Posted: July 18, 2008
Results First Submitted: May 31, 2017
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018