A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia.

Percentage of Participants With Best Overall Response (BOR) of Clinical CR or Confirmed CR

Clinical CR was achieved if all of the following criteria were met: a)Absence of lymphadenopathy (LD) by physical examination (PE) and Computed Tomography (CT) scan (all lymph nodes less than \[\<\] 1.5 centimeters \[cm\] in diameter), b)No hepatomegaly (HM)/splenomegaly (SM) by PE/CT scan, c)Absence of B symptoms (unexplained fever greater than \[\>\] 38 degrees \[°\] Centigrade \[C\], drenching night sweats/\>10 percent \[%\] body weight loss in the last 6 months), d)Normal Complete Blood Count (CBC) (i. Leukocytes (Leuk) greater than or equal to \[≥\] 1.5×10\^9 per liter (/L), ii. Platelets (Plat) \>100×10\^9/L, and iii. Haemoglobin (Hb) \>11.0 grams per deciliter \[g/dL\]) and e)Once clinical, radiological and laboratory evaluations demonstrated CR, bone marrow (BM) biopsy and aspirate were performed 8 weeks later for confirmation; BM sample: normocellular for age, \<30% of the cells being lymphocytes (Lym) and lymphoid nodules (LN) absent was considered as a confirmed CR.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants With BOR of Partial Response (PR)

PR was achieved if all of the following criteria were met: a)≥50% decrease in Lym count from the baseline value, b)≥50% reduction in LD by CT scan, c)≥50% reduction in size of liver/spleen by PE/CT scan and at least 1 of the following for a minimum of 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. Participants who fulfilled criteria for CR with persistent anemia/thrombocytopenia were considered in PRs. CR was achieved if all of the criteria were fulfilled for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants With BOR of Nodular Partial Response (nPR)

CR was achieved if all of the following criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. Participants with nPR were those who satisfied all of the CR criteria except for the BM, where LN could be identified histologically.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants With BOR of Progressive Disease (PD)

PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of hepatosplenomegaly (HSM) as determined by PE/CT scan; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants With BOR of Stable Disease (SD)

Participants without CR/PR or PD were considered having a tumor response of SD. CR: a) Absence of LD by PE and CT, b) No HM/SM by PE/CT, c) Absence of B symptoms, d) Normal CBC, and e) BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR: a) ≥50% decrease in Lym count from baseline, b) ≥50% reduction in LD, c) ≥50% reduction in size of liver/spleen by PE/CT and ≥1 of the following for at least 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. PD: a) ≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size or appearance of new lymph nodes/extranodal lesions, or b) ≥50% increase in the size of HSM; new appearance of palpable HM/SM, or c) ≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, or d) Transformation to a more aggressive histology.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants With Objective Response (CR or PR)

Objective response was defined as a tumor response of CR or PR. CR was achieved if all of the criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR was achieved if all of the criteria were met: a)≥50% decrease in Lymp count from the baseline value, b)≥50% reduction in LD by CT scan, c)≥50% reduction in size of liver/spleen by PE/CT scan and at least 1 of the following for a minimum of 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. Participants who fulfilled criteria for CR with persistent anemia/thrombocytopenia were considered PRs.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participant With Disease Progression or Death

PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of HSM as determined by PE/CT scan; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Progression Free Survival (PFS) Time

PFS was defined as the interval (in days) from trial treatment start date to earlier of the date of first tumor response assessment of PD or date of death by any cause. Participants who experienced none of these events or who were lost to follow-up at the time of analysis were censored on last date when they were assessed for tumor response. PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of HSM as determined by PE/CT; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Disease Free Survival (DFS) Time

DFS time was defined as interval (in days) from first tumor response of CR to date of first tumor response of PD, or date of death by any cause. Participants who experienced none of these events or who were lost to follow-up at the time of analysis were censored on last date when they were assessed for tumor response. CR: a) Absence of LD by PE and CT, b) No HM/SM by PE/CT, c) Absence of B symptoms, d) Normal CBC, and e) BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PD: a) ≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size or appearance of new lymph nodes/extranodal lesions, or b) ≥50% increase in the size of HSM; new appearance of palpable HM/SM, or c) ≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, or d) Transformation to a more aggressive histology.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Duration of Response (DoR)

DoR: defined as interval (in days) from first tumor response (of CR/PR/nPR) to earlier of date of PD/death. Participants without PD/death or who were lost to follow-up were censored. CR: a)Absence of LD by PE and CT, b)No HM/SM by PE/CT, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR: a)≥50% decrease in Lym count from baseline value, b)≥50% reduction in LD, c)≥50% reduction in size of liver/spleen by PE/CT scan and d)Leuk, Plat and Hb ≥1.5×10\^9/L, \>100×10\^9/L and \>11.0 g/dL, respectively or 50% improvement (of all the 3) over baseline value. nPR: participants who satisfied all of CR criteria except for BM, where LN could be identified. PD: a)≥50% increase in sum of the products of ≥2 lymph nodes or appearance of new lymph nodes/extranodal lesions, or b)≥50% increase in size of HSM; new appearance of palpable HM/SM, or c)≥50% increase in number of Lym, or d)Transformation to a more aggressive histology.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants Who Died

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Overall Survival (OS) Time

This was defined as the interval (number of days) from the trial treatment start date to the date of death by any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Percentage of Participants Who Achieved Minimal Residual Disease (MRD) Negativity

MRD negativity was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. MRD was assessed in participants with a confirmed CR. CR was achieved if all of the following criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent.

Time frame: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)

Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores

EORTC QLQ-C30: included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global Qol/functional scales=better level of QoL/functioning, or a higher score for symptom scale=greater degree of symptoms.

Time frame: Baseline, Day 1 of Cycles 5 and 11, end of follow-up (FU) (24 month [m] FU visit, up to approximately 3 years)