Lymphocytic Leukemia, Chronic
Conditions
Brief summary
This study will assess the effect of maintenance treatment with rituximab in comparison with observation period (no treatment), in participants with progressive B-cell CLL who have had previous first-line induction treatment with rituximab, cladribine and cyclophosphamide (RCC regimen). After 6 months of RCC induction therapy, participants will be randomized either to receive maintenance treatment with rituximab or to receive no treatment (observation only) for 96 weeks. Participants completing maintenance/observation period will be followed-up for approximately 3 years.
Interventions
DRUGCladribine
Cladribine will be adminiatered at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4 of each 28-day cycle during induction phase.
DRUGCyclophosphamide
Cyclophosphamide will be administred at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes on Days 2-4 of each 28-day cycle during induction phase.
DRUGRituximab
Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 during induction phase. Rituximab will be administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle during maintenance phase.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Immunologically confirmed diagnosis of B-cell CLL * Rai stage I-IV disease with evidence of progression * No previous chemotherapy, radiotherapy, or immunotherapy for B-cell CLL * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Exclusion criteria
* Active secondary malignancy or transformation to aggressive lymphoma * Medical condition requiring chronic use of oral corticosteroids at a dose of 1 mg/kg or 60 mg/m\^2 over 2 weeks * Prior treatment with interferon, rituximab or another monoclonal antibody, immunosuppressive treatment or radiotherapy before inclusion to the study * History of other malignancies within 2 years before study entry, except for dequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | From randomization to PD, Relapse, or death due to any cause (overall approximately 5 years) | 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. |
| Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | From randomization to PD, relapse, or death due to any cause (overall approximately 5 years) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | From randomization to PD, relapse, or death due to any cause (overall approximately 5 years) | 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. |
| 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 | 8 weeks after the last dose of rituximab during induction treatment (Week 29) | 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. |
| Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | 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) | 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). |
| Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | 8 weeks after the last dose of rituximab during induction treatment (Week 29) | 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. |
| Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | 12 weeks after the end of maintenance treatment or observation phase (Week 129) | 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. |
| 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 | 12 weeks after the end of maintenance treatment or observation phase (Week 129) | 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. |
| Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR | 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) | 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). |
Countries
Belarus, Poland
Participant flow
Pre-assignment details
A total 136 participants were screened, out of which 128 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Induction: Rituximab, Cladribine, Cyclophosphamide 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. | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Induction Phase | Disease Progression | 1 | 0 | 0 |
| Induction Phase | Early Termination - No Additional Info | 59 | 0 | 0 |
| Induction Phase | Eligibility Criteria Violation | 2 | 0 | 0 |
| Maintenance/ Observation Phase | Death | 0 | 1 | 2 |
| Maintenance/ Observation Phase | Early Termination - No Additional Info | 0 | 15 | 8 |
| Maintenance/ Observation Phase | Lost to Follow-up | 0 | 4 | 4 |
| Maintenance/ Observation Phase | Progression | 0 | 5 | 14 |
| Maintenance/ Observation Phase | Relapse | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Induction: Rituximab, Cladribine, Cyclophosphamide |
|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 62 | 31 / 33 | 32 / 33 | 121 / 128 |
| serious Total, serious adverse events | 23 / 62 | 13 / 33 | 9 / 33 | 45 / 128 |
Outcome results
Primary
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)
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Arm: Rituximab | 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) | 27.3 percentage of participants |
| Observation Arm: No Intervention | 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) | 54.5 percentage of participants |
| All Randomized Participants | 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) | 40.9 percentage of participants |
Primary
Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
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)
Population: ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maintenance Arm: Rituximab | Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | NA years |
| Observation Arm: No Intervention | Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | 2.1 years |
| All Randomized Participants | Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | 3.1 years |
p-value: 0.028Log Rank
Comparison: Univariate comparisonp-value: 0.03395% CI: [0.187, 0.933]Cox's proportional hazards regression
Comparison: Multivariate Comparisonp-value: 0.11195% CI: [0.001, 1.972]Cox's proportional hazards model
Secondary
Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | Week 129 | 90.5 percentage of participants |
| Observation Arm: No Intervention | Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | Week 129 | 72.2 percentage of participants |
| All Randomized Participants | Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | Week 29 | 73.2 percentage of participants |
| All Randomized Participants | Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL | Week 129 | 82.1 percentage of participants |
Comparison: Week 129: Univariate Comparisonp-value: 0.15595% CI: [0.674, 28.337]Regression, Logistic
Secondary
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
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | 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 | Age >/=60 years | 84.6 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Sex: Female | 85.7 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Rai Stage: III or IV | 87.5 percentage of participants |
| Maintenance Arm: Rituximab | 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 | CD38 Expression: Positive | 75.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 17p: Yes | 50.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 12q: No | 76.2 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Age <60 years | 80.8 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Sex: Male | 80.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Rai Stage: I or II | 80.6 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Beta-2-Microglobulin >/= Median Value | 76.9 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Beta-2-Microglobulin <Median Value | 84.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | ZAP-70 Expression: Negative | 83.3 percentage of participants |
| Maintenance Arm: Rituximab | 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 | ZAP-70 Expression: Positive | 83.3 percentage of participants |
| Maintenance Arm: Rituximab | 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 | CD38 Expression: Negative | 77.8 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 17p: No | 86.7 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 13q: No | 90.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 13q: Yes | 76.5 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 11q: No | 84.2 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 11q: Yes | 80.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 12q: Yes | 100.0 percentage of participants |
Comparison: Univariate Comparison: Age \<60 years versus Age \>/=60 yearsp-value: 0.76895% CI: [0.237, 10.189]Regression, Logistic
Comparison: Univariate Comparison: Sex: Female versus Malep-value: 0.65795% CI: [0.086, 3.653]Regression, Logistic
Comparison: Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IVp-value: 0.65595% CI: [0.229, 34.486]Regression, Logistic
Comparison: Univariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Valuep-value: 0.59595% CI: [0.117, 3.73]Regression, Logistic
Comparison: Univariate Comparison: ZAP-70 Expression Negative versus Positivep-value: 195% CI: [0.164, 8.102]Regression, Logistic
Comparison: Univariate Comparison: CD38 Expression Negative versus Positivep-value: 0.88295% CI: [0.093, 6.636]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 17p No versus Yesp-value: 0.21695% CI: [0.005, 4.405]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 13q No versus Yesp-value: 0.39695% CI: [0.017, 2.971]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 11q No versus Yesp-value: 0.77695% CI: [0.103, 6.572]Regression, Logistic
Secondary
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
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | 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 | Age <60 years | 73.3 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Sex: Female | 80.6 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Sex: Male | 69.7 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Rai Stage: I or II | 77.5 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Rai Stage: III or IV | 61.5 percentage of participants |
| Maintenance Arm: Rituximab | 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 | CD38 Expression: Negative | 73.1 percentage of participants |
| Maintenance Arm: Rituximab | 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 | CD38 Expression: Positive | 71.4 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 17p: No | 72.8 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 11q: Yes | 79.2 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Age >/=60 years | 73.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Beta-2-Microglobulin >/= Median Value | 64.6 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Beta-2-Microglobulin <Median Value | 83.0 percentage of participants |
| Maintenance Arm: Rituximab | 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 | ZAP-70 Expression: Negative | 67.1 percentage of participants |
| Maintenance Arm: Rituximab | 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 | ZAP-70 Expression: Positive | 94.7 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 17p: Yes | 71.4 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 13q: No | 62.9 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 13q: Yes | 76.1 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 11q: No | 69.5 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 12q: No | 67.6 percentage of participants |
| Maintenance Arm: Rituximab | 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 | Cytogenetic abnormality 12q: Yes | 66.7 percentage of participants |
Comparison: Univariate Comparison: Age \<60 years versus Age \>/=60 yearsp-value: 0.96995% CI: [0.393, 2.531]Regression, Logistic
Comparison: Univariate Comparison: Sex: Female versus Malep-value: 0.2695% CI: [0.183, 1.488]Regression, Logistic
Comparison: Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IVp-value: 0.12195% CI: [0.177, 1.242]Regression, Logistic
Comparison: Univariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Valuep-value: 0.04595% CI: [0.137, 0.957]Regression, Logistic
Comparison: Univariate Comparison: ZAP-70 Expression Negative versus Positivep-value: 0.0495% CI: [1.655, 163.316]Regression, Logistic
Comparison: Univariate Comparison: CD38 Expression Negative versus Positivep-value: 0.88795% CI: [0.287, 2.851]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 17p No versus Yesp-value: 0.93695% CI: [0.186, 6.839]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 13q No versus Yesp-value: 0.19995% CI: [0.719, 5.012]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 11q No versus Yesp-value: 0.37595% CI: [0.566, 5.649]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 12q No versus Yesp-value: 0.96195% CI: [0.173, 7.275]Regression, Logistic
Secondary
Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR | Week 129 | 28.6 percentage of participants |
| Observation Arm: No Intervention | Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR | Week 129 | 20.0 percentage of participants |
| All Randomized Participants | Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR | Week 29 | 15.4 percentage of participants |
| All Randomized Participants | Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR | Week 129 | 25.0 percentage of participants |
Comparison: Week 129: Univariate comparisonp-value: 0.63495% CI: [0.073, 4.114]Regression, Logistic
Secondary
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Age <60 years | 72.2 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Age >/=60 years | 83.3 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Sex: Female | 71.4 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 11q: No | 66.7 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 12q: No | 66.7 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Sex: Male | 76.5 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Rai Stage: I or II | 75.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Rai Stage: III or IV | 75.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Beta-2-Microglobulin >/= Median Value | 88.9 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Beta-2-Microglobulin <Median Value | 71.4 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | ZAP-70 Expression: Negative | 66.7 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | ZAP-70 Expression: Positive | 100.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | CD38 Expression: Negative | 60.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | CD38 Expression: Positive | 77.8 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 17p: No | 76.2 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 17p: Yes | 0.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 13q: No | 75.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 13q: Yes | 66.7 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 11q: Yes | 75.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129 | Cytogenetic abnormality 12q: Yes | 66.7 percentage of participants |
Comparison: Univariate Comparison: Age \<60 years versus Age \>/=60 yearsp-value: 0.59195% CI: [0.225, 41.751]Regression, Logistic
Comparison: Univariate Comparison: Sex: Female versus Malep-value: 0.79695% CI: [0.147, 9.222]Regression, Logistic
Comparison: Univariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Valuep-value: 0.33895% CI: [0.375, 69.479]Regression, Logistic
Comparison: Univariate Comparison: CD38 Expression Negative versus Positivep-value: 0.48695% CI: [0.201, 29.008]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 13q No versus Yesp-value: 0.69195% CI: [0.074, 4.722]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 11q No versus Yesp-value: 0.69195% CI: [0.212, 13.563]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 12q No versus Yesp-value: 195% CI: [0.076, 24.621]Regression, Logistic
Comparison: Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IVp-value: 195% CI: [0.099, 22.791]Regression, Logistic
Secondary
Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 17p: No | 83.6 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Age <60 years | 87.8 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Age >/=60 years | 79.2 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Sex: Female | 87.5 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Sex: Male | 82.9 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Rai Stage: I or II | 80.4 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Rai Stage: III or IV | 100.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Beta-2-Microglobulin >/= Median Value | 93.1 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Beta-2-Microglobulin <Median Value | 77.1 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | ZAP-70 Expression: Negative | 82.6 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | ZAP-70 Expression: Positive | 100.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | CD38 Expression: Negative | 83.3 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | CD38 Expression: Positive | 95.5 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 17p: Yes | 100.0 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 13q: No | 84.2 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 13q: Yes | 81.8 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 11q: No | 83.3 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 11q: Yes | 84.2 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 12q: No | 80.5 percentage of participants |
| Maintenance Arm: Rituximab | Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29 | Cytogenetic abnormality 12q: Yes | 75.0 percentage of participants |
Comparison: Univariate Comparison: Age \<60 years versus Age \>/=60 yearsp-value: 0.35795% CI: [0.131, 2.114]Regression, Logistic
Comparison: Univariate Comparison: Sex: Female versus Malep-value: 0.62395% CI: [0.138, 2.8]Regression, Logistic
Comparison: Univariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Valuep-value: 0.09795% CI: [0.901, 28.158]Regression, Logistic
Comparison: Univariate Comparison: CD38 Expression Negative versus Positivep-value: 0.23395% CI: [0.484, 89.588]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 13q No versus Yesp-value: 0.82695% CI: [0.161, 3.681]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 11q No versus Yesp-value: 0.93395% CI: [0.246, 5.581]Regression, Logistic
Comparison: Univariate Comparison: Cytogenetic abnormality 12q No versus Yesp-value: 0.79495% CI: [0.08, 15.779]Regression, Logistic
Secondary
PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Sex: Female | 4.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Sex: Male | 3.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Beta-2-Microglobulin <Median Value | NA years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 11q: Yes | 2.8 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Age <60 years | 3.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Age >/=60 years | 4.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Rai Stage: I or II | 3.1 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Rai Stage: III or IV | 3.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Beta-2-Microglobulin >/= Median Value | 1.9 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Zeta-Associated Protein (ZAP)-70: Negative | 3.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | ZAP-70 Expression: Positive | NA years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | CD38 Expression: Negative | 2.1 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | CD38 Expression: Positive | 2.8 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 17p: No | 3.1 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 17p: Yes | 1.9 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 13q: No | 3.5 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 13q: Yes | 3.0 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 11q: No | 3.5 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 12q: No | 2.2 years |
| Maintenance Arm: Rituximab | PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors | Cytogenetic abnormality 12q: Yes | 3.1 years |
Comparison: Multivariate Comparison: Age \<60 years versus Age \>/=60 yearsp-value: 0.75295% CI: [0.151, 3.92]Cox's proportional hazards model
Comparison: Multivariate Comparison: Sex: Female versus Malep-value: 0.12895% CI: [0.002, 2.158]Cox's proportional hazards model
Comparison: Multivariate Comparison: Rai Stage: I or II versus Rai Stage: III or IVp-value: 0.72895% CI: [0.022, 240.864]Cox's proportional hazards model
Comparison: Multivariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Valuep-value: 0.04895% CI: [1.036, 666.708]Cox's proportional hazards model
Comparison: Multivariate Comparison: ZAP-70 Expression Negative versus Positivep-value: 0.41795% CI: [0.005, 9.1]Cox's proportional hazards model
Comparison: Multivariate Comparison: CD38 Expression Negative versus Positivep-value: 0.13495% CI: [0.024, 1.647]Cox's proportional hazards model
Comparison: Multivariate Comparison: Cytogenetic abnormality 17p No versus Yesp-value: 0.42695% CI: [0.045, 1568.717]Cox's proportional hazards model
Comparison: Multivariate Comparison: Cytogenetic abnormality 13q No versus Yesp-value: 0.73395% CI: [0.004, 50.334]Cox's proportional hazards model
Comparison: Multivariate Comparison: Cytogenetic abnormality 11q No versus Yesp-value: 0.46395% CI: [0.2, 34.422]Cox's proportional hazards model
Comparison: Multivariate Comparison: Cytogenetic abnormality 12q No versus Yesp-value: 0.39795% CI: [0.016, 5.122]Cox's proportional hazards model