A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL)

CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (\<) 4000 per cubic millimeter (mm\^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (\>) 1500/mm\^3, platelets (Plt) \>100,000/mm\^3, hemoglobin (Hb) \>11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.

Time frame: Month 9

Population: ITT Population included all participants who received at least one dose of study drug and met inclusion/exclusion criteria.

DOR: time from CR/PR to MRD/PD. PD: new ADP (1.5 cm), HSM, RS, other infiltrated organs or \>/=50% increase size in those with PR; blood Lymph increase \>/=50% with B Lymph \>/=5000/mm\^3; cytopenia due to CLL. Progression of (nonautoimmune) cytopenia: 2-g/dL decrease basal Hb, Hb \<10 g/dL, \>/=50% decrease basal Plt or \<100,000/mm\^3 at \>/=3 months post-treatment was PD if clonal CLL cell infiltration on BM biopsy. CR: no ADP/VSM in PE; no general Sx; blood Lymph \<4000/mm\^3; Neut \>1500/mm\^3; Plt \>100,000/mm\^3; Hb \>11 g/dL (no transfusion); normocellular BM with \<30% Lymph; BM aspirate/biopsy with no lymphoid nodule infiltration. PR: \>50% decrease blood Lymph; \>50% decrease in total sum up to 6 ADPs or baseline ADP of LD, no new/enlargement of prior ADP; \>50% decrease VSM; Neut \>1500/mm\^3 or \>50% increase; Plt \>100,000/mm\^3 or \>50% increase; Hb \>11.0 g/dL or \>50% increase (no transfusion). All CR criteria but persistent anemia or thrombocytopenia was PR. MRD: Lymph \>0.01% of blood/BM WBCs.

Time frame: From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)

Population: ITT Population. Only those participants who achieved a clinical response of CR or PR were evaluable for this measure.

OS was defined as time from treatment start to death of the participant. For all other participants, the last follow-up available was taken as the last control. If the participant had not completed the study, the date of the last visit available was considered. OS was estimated using Kaplan-Meier (KM) methodology.

Time frame: Baseline up to death due to any cause (up to 92 months)

Population: ITT Population

Time frame: Baseline up to death due to any cause (up to 92 months)

Population: Safety Population

CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR: decrease \>50% in Lymph in peripheral blood; reduction in ADPs \>50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; \>50% decrease in VSM; Neut \>1500/mm\^3 or \>50% increase from Baseline; Plt \>100,000/mm\^3 or \>50% increase from Baseline; Hb \>11.0 g/dL or \>50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR. Negative MRD: Lymph \<0.01% of all white blood cells (WBCs) in blood or BM after two consecutive measurements. Analysis performed only in blood during the Maintenance Phase and Follow-Up.

Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36

Population: ITT Population. Only those with negative MRD were included in the analysis. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.

CR was defined as no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR was defined as decrease \>50% in Lymph in peripheral blood; reduction in ADPs \>50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; \>50% decrease in VSM; Neut \>1500/mm\^3 or \>50% increase from Baseline; Plt \>100,000/mm\^3 or \>50% increase from Baseline; Hb \>11.0 g/dL or \>50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR.

Time frame: Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36

Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.

Percentages of participants with CD38 expression by \>/=30% of CLL cells during the Induction Phase, Maintenance Phase, and Follow-Up were reported.

Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36

Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.

Participants with CRi were those who met all CR criteria (including BM examinations) but had persistent anemia, thrombocytopenia, or neutropenia apparently unrelated to chronic lymphocytic leukemia (CLL) but related to drug toxicity. CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.

Time frame: Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)

Population: ITT Population

Percentages of participants with genetic abnormalities (deletion 6q, deletion 11q22-q23, deletion p53, trisomy 12, and deletion 13q14) in the course of the disease during the Induction Phase and Maintenance Phase were reported.

Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)

Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category. Designation of 'MP (xC)' refers to number of cycles in Maintenance Phase.

Percentages of participants with IgH rearrangement during the Induction Phase, Maintenance Phase, and Follow-Up were reported.

Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36

Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.

PD was defined as new ADPs (1.5 centimeters \[cm\]), hepato-/splenomegaly (HSM), Richter syndrome (RS), or other infiltrated organs; greater than or equal to (\>/=) 50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.

Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)

Population: ITT Population

Percentages of participants with positive and negative ZAP-70 expression during the Induction Phase, Maintenance Phase, and Follow-Up were reported. Positive ZAP-70 was defined as ZAP-70 expression by \>/=20% of CLL cells. Negative ZAP-70 was defined as ZAP-70 expression by \<20% of CLL cells.

Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36

Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.

PFS was defined as time from start of study treatment to PD or death, whichever occurred first. For other participants, last follow-up available was taken as last control. If participant did not complete study, date of last visit available was considered. PFS was estimated using KM methodology. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; \>/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.

Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)

Population: ITT Population

TFS was defined time from start of study treatment until participant received new chemotherapy/immunotherapy because of PD and to reduce the disease with palliative or curative intent. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; \>/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.

Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)

Population: ITT Population. Only those who received new chemotherapy/immunotherapy, as per definitions for TFS, were included in the analysis.