A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL.

Official Title
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A Multicenter, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Rituximab Plus Fludarabine and Cyclophosphamide (FCR) as First-Line Treatment in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)

Conditions
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Lymphocytic Leukemia, Chronic

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants greater than or equal to (≥) 18 years of age B-cell CLL No previous treatment for leukemia Exclusion Criteria: History of other malignancies within 2 years before study entry, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, prostate cancer, or breast cancer Comorbid condition requiring long-term (greater than [>] 1 month) systemic corticosteroids during study treatment Known infection with hepatitis B or C virus or with human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab + Fludarabine + Cyclophosphamide<br>Participants will receive rituximab (375 milligrams per meter-squared [mg/m^2] intravenously [IV]) on Cycle 1 Day 1, followed by fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) for Days 2 to 4 of Cycle 1. Then rituximab (500 mg/m^2 IV) will be administered on Day 1 of Cycles 2 to 6, followed by IV fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) on Days 1 to 3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length, and the overall duration of treatment will be approximately 6 months. | Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered IV at 250 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.<br>Drug: Fludarabine<br>* Fludarabine will be administered IV at 25 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.<br>Drug: Rituximab<br>* Rituximab will be administered IV at 375 mg/m^2 on Day 1 of Cycle 1 and then at 500 mg/m^2 on Day 1 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.<br>* Other names: MabThera/Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Death or Disease Progression | Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated. | Up to 5 years (from Baseline until disease progression or death, whichever occurred first) | 
| Progression-Free Survival (PFS) | Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis. | Up to 5 years (from Baseline until disease progression or death, whichever occurred first) | 
| Percentage of Participants Who Died | Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated. | Up to 5 years (from Baseline until death) | 
| Overall Survival (OS) | Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis | Up to 5 years (from Baseline until death) | 
| Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR) | Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (<) 4000 cells per cubic millimeter (cells/mm^3), neutrophils greater than (>) 1500 cells/mm^3, platelets >100,000 cells/mm^3, bone marrow (BM) biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as >50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated. | Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up) |