Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Chlorambucil

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants will receive combination therapy of rituximab plus chlorambucil for first 6 cycles and then chlorambucil alone for a maximum of 6 additional cycles.

375mg/m\^2 IV on Day 1 of Cycle 1; 500mg/m\^2 on Day 1 of Cycles 2-6.

10 mg/m\^2/day PO on Days 1 to 7 of each cycle for a maximum of 12 cycles.

Clinical Trials

This single arm study will assess the safety and effect on response rate of a combination of rituximab and chlorambucil in previously untreated participants with B-cell chronic lymphocytic leukemia. Participants will receive 6 monthly cycles of combination treatment, followed by up to 6 cycles of chlorambucil alone. Rituximab will be administered on Day 1 of each cycle, at a dose of 375 milligrams per square meter (mg/m\^2) intravenously (IV) in Cycle 1, and 500 mg/m\^2 in subsequent cycles, and chlorambucil will be administered on Days 1-7 of each cycle at a dose of 10 mg/m\^2/day per oral (PO).

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

An Open-Label Study to Characterize the Safety and Response Rate of MabThera (Rituximab) Plus Chlorambucil in Previously Untreated Patients With CD20-Positive B-Cell Chronic Lymphocytic Leukemia

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 56 days from the beginning of the last treatment cycle that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs as well as non-serious AEs.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Hoffmann-La Roche

Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.

Rituximab + Chlorambucil

Age, Continuous

Sex: Female, Male

Full analysis set (FAS) comprised all participants recruited into the study and known to have received at least one dose of study treatment.

Medical Communications

Percentage of Participants With Treatment-Emergent Adverse Events (AEs)

Clinical CR

Confirmed CR

Clinical CR or Confirmed CR

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

Percentage of Participants With BOR of Partial Response (PR)

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

Percentage of Participants With BOR of Progressive Disease (PD)

Percentage of Participants With BOR of Stable Disease (SD)

Percentage of Participants With Objective Response (CR or PR)

Percentage of Participant With Disease Progression or Death

Progression Free Survival (PFS) Time

FAS population participants who achieved confirmed CR.

Disease Free Survival (DFS) Time

FAS population participants who achieved confirmed CR, PR or nPR.

Duration of Response (DoR)

Percentage of Participants Who Died

Overall Survival (OS) Time

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

CFB in GHS/QoL statistical analysis at Cycle 5.

CFB in GHS/QoL statistical analysis at Cycle 11.

CFB in GHS/QoL statistical analysis at end of FU.

CFB in physical functioning statistical analysis at Cycle 5.

CFB in physical functioning statistical analysis at Cycle 11.

CFB in physical functioning statistical analysis at end of FU.

CFB in role functioning statistical analysis at Cycle 5.

CFB in role functioning statistical analysis at Cycle 11.

CFB in role functioning statistical analysis at end of FU.

CFB in emotional functioning statistical analysis at Cycle 5.

CFB in emotional functioning statistical analysis at Cycle 11.

CFB in emotional functioning statistical analysis at end of FU.

CFB in cognitive functioning statistical analysis at Cycle 5.

CFB in cognitive functioning statistical analysis at Cycle 11.

CFB in cognitive functioning statistical analysis at end of FU.

CFB in social functioning statistical analysis at Cycle 5.

CFB in social functioning statistical analysis at Cycle 11.

CFB in social functioning statistical analysis at end of FU.

CFB in fatigue statistical analysis at Cycle 5.

CFB in fatigue functioning statistical analysis at Cycle 11.

CFB in fatigue statistical analysis at end of FU.

CFB in Nausea/vomiting statistical analysis at Cycle 5.

CFB in nausea/vomiting statistical analysis at Cycle 11.

CFB in nausea/vomiting statistical analysis at end of FU.

CFB in pain statistical analysis at Cycle 5.

CFB in pain statistical analysis at Cycle 11.

CFB in pain statistical analysis at end of FU.

GHS/QoL score-baseline (n=91)

CFB in GHS/QoL Score-Cycle 5 (n=59)

CFB in GHS/QoL Score-Cycle 11 (n=40)

CFB in GHS/QoL Score-24m FU (n=17)

Physical functioning score-baseline (n=91)

CFB in physical functioning score-Cycle 5 (n=59)

CFB in physical functioning score-Cycle 11 (n=40)

CFB in physical functioning score-24m FU (n=17)

Role functioning score-baseline (n=91)

CFB in role functioning score-Cycle 5 (n=59)

CFB in role functioning score-Cycle 11 (n=40)

CFB in role functioning score-24m FU (n=17)

Emotional functioning score-baseline (n=91)

CFB in emotional functioning score-Cycle 5 (n=59)

CFB in emotional functioning score-Cycle 11 (n=40)

CFB in emotional functioning score-24m FU (n=17)

Cognitive functioning score-baseline (n=91)

CFB in cognitive functioning score-Cycle 5 (n=59)

CFB in cognitive functioning-Cycle 11 (n=40)

CFB in cognitive functioning-24m FU (n=17)

Social functioning score-baseline (n=91)

CFB in social functioning score-Cycle 5 (n=59)

CFB in social functioning score-Cycle 11 (n=40)

CFB in social functioning score-at 24m FU (n=17)

Fatigue score-baseline (n=91)

CFB in fatigue score-Cycle 5 (n=59)

CFB in fatigue score-Cycle 11 (n=40)

CFB in fatigue score-24m FU (n=17)

Nausea/vomiting score-baseline (n=91)

CFB in nausea/vomiting score-Cycle 5 (n=59)

CFB in nausea/vomiting score-Cycle 11 (n=40)

CFB in nausea/vomiting score-24m FU (n=17)

Pain score-baseline (n=91)

CFB in pain score-Cycle 5 (n=59)

CFB in pain score-Cycle 11 (n=40)

CFB in pain score-24m FU (n=17)

FAS. Number of participants analyzed = number of participants evaluable for this outcome and n=number of participants evaluable at the specified time point.

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

Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles (28 day cycles). Participants who did not achieve complete response (CR) after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 milligrams per square meter per day (mg/m\^2/day) oral administration (PO) on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.

Spots Global Cancer Trial Database for A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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