Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Disease Progression

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

Cyclophosphamide

Rituximab

Cladribine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Participants will receive rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes 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 minutes on Days 2-4 will be administered in Cycles 2-6. Each cycle will be of 28 days in duration.

Participants with PR or CR after induction phase who will be randomized to maintenance arm will receive rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants will receive rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).

Participants with PR or CR after induction phase who will be randomized to observation arm will not receive any intervention. Participants will be assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.

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.

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.

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.

Clinical Trials

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.

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

A Randomized, Open Label Study to Assess the Effect of Maintenance Treatment With Mabthera (Rituximab) Versus No Treatment, After Induction Treatment With Rituximab, Cladribine and Cyclophosphamide (RCC) on Progression-Free Survival in Previously Untreated Patients With Progressive B-Cell Chronic Lymphocytic Leukemia

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.

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.

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).

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).

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.

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.

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.

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.

Hoffmann-La Roche

All enrolled participants who received at least one dose of study medication were included in the analysis.

Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration. Only participants who were not randomized to maintenance or observation arm were included.

Induction (Excluding Maintenance/ Observation)

Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to maintenance arm received rituximab treatment for 8 cycles. Twelve weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle until disease progression (up to approximately 96 weeks).

Maintenance Arm: Rituximab

Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase who were randomized to observation arm did not receive any intervention. Participants were assessed every 4-weeks for the first 12 weeks and every 12-weeks afterwards up to 96 weeks.

Observation Arm: No Intervention

All Participants

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.

Induction: Rituximab, Cladribine, Cyclophosphamide

Age, Continuous

Sex: Female, Male

All enrolled participants who received at least one dose of study medication.

In 2011 the recruitment was stopped due to low enrollment rate, and in 2015 the trial was prematurely discontinued.

Medical Communications

Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).

All Randomized Participants

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.

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)

ITT population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Progression-Fee Survival (PFS) Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL

Week 29

Week 129

Participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6, along with cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 of each 28-days cycle for 6 cycles during induction phase. Participants with PR or CR after induction phase were randomized to observation arm (received no intervention) or to maintenance arm (12 weeks after the last induction cycle, participants received rituximab at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles or until disease progression \[up to approximately 96 weeks\]).

Overall 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.

Percentage of Participants With CR or PR Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL

Percentage of Participants With Minimal Residual Disease (MRD) According to Rawstron Criteria in Participants With CR or PR

Multivariate Comparison: Age \<60 years versus Age \>/=60 years

Multivariate Comparison: Sex: Female versus Male

Multivariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV

Multivariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Value

Multivariate Comparison: ZAP-70 Expression Negative versus Positive

Multivariate Comparison: CD38 Expression Negative versus Positive

Multivariate Comparison: Cytogenetic abnormality 17p No versus Yes

Multivariate Comparison: Cytogenetic abnormality 13q No versus Yes

Multivariate Comparison: Cytogenetic abnormality 11q No versus Yes

Multivariate Comparison: Cytogenetic abnormality 12q No versus Yes

Age <60 years

Age >/=60 years

Sex: Female

Sex: Male

Rai Stage: I or II

Rai Stage: III or IV

Beta-2-Microglobulin >/= Median Value

Beta-2-Microglobulin <Median Value

Zeta-Associated Protein (ZAP)-70: Negative

ZAP-70 Expression: Positive

CD38 Expression: Negative

CD38 Expression: Positive

Cytogenetic abnormality 17p: No

Cytogenetic abnormality 17p: Yes

Cytogenetic abnormality 13q: No

Cytogenetic abnormality 13q: Yes

Cytogenetic abnormality 11q: No

Cytogenetic abnormality 11q: Yes

Cytogenetic abnormality 12q: No

Cytogenetic abnormality 12q: Yes

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.

PFS Assessed According to the NCI Revised Guidelines for the Diagnosis and Treatment of CLL According to Clinical and Biochemical Factors

Univariate Comparison: Age \<60 years versus Age \>/=60 years

Univariate Comparison: Sex: Female versus Male

Univariate Comparison: Rai Stage: I or II versus Rai Stage: III or IV

Univariate Comparison: Beta-2-Microglobulin \>/= Median Value versus Beta-2-Microglobulin \<Median Value

Univariate Comparison: ZAP-70 Expression Negative versus Positive

Univariate Comparison: CD38 Expression Negative versus Positive

Univariate Comparison: Cytogenetic abnormality 17p No versus Yes

Univariate Comparison: Cytogenetic abnormality 13q No versus Yes

Univariate Comparison: Cytogenetic abnormality 11q No versus Yes

Univariate Comparison: Cytogenetic abnormality 12q No versus Yes

ZAP-70 Expression: Negative

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.

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

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

Participants with PR or CR after induction phase were randomized to either observation arm (received no intervention) or to maintenance arm (received maintenance treatment with rituximab administered at a dose of 375 mg/m\^2 as IV infusion on Day 1 of each 12-week cycle for 8 cycles until disease progression for up to approximately 96 weeks).

Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 29

Percentage of Participants With MRD According to Rawstron Criteria in Participants With CR or PR According to Clinical and Biochemical Factors at Week 129

Participants received rituximab at a dose of 375 milligrams per meter squared (mg/m\^2) as intravenous (IV) infusion on Day 1, cladribine at a dose of 0.12 milligrams per kilogram per day (mg/kg/day) as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 minutes (min) on Days 2-4 in Cycle 1. Then, rituximab at a dose of 500 mg/m\^2 as IV infusion on Day 1, cladribine at a dose of 0.12 mg/kg/day as IV infusion on Days 2-4, and cyclophosphamide at a dose of 250 mg/m\^2/day as IV infusion over 15-30 min on Days 2-4 were administered in Cycles 2-6. Each cycle was of 28 days in duration.

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

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Study Description

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