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

Phase 2

Completed

• Conditions: Lymphocytic Leukemia, Chronic
• Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

• Registration Number: NCT02533401
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Study First Submitted: 2015-08-24
• Study First Submitted QC: 2015-08-24
• Study First Posted: 2015-08-26
• Status Verified: 2016-03
• Results First Submitted: 2016-03-29
• Results First Submitted QC: 2016-03-30
• Last Update Submitted: 2016-03-30
• Results First Posted: 2016-05-02
• Last Update Posted: 2016-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Adult participants greater than or equal to (≥) 18 years of age
• B-cell CLL
• No previous treatment for leukemia

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rituximab + Fludarabine + Cyclophosphamide	Cyclophosphamide	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.
Rituximab + Fludarabine + Cyclophosphamide	Fludarabine	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.
Rituximab + Fludarabine + Cyclophosphamide	Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 5 years (from Baseline until death)	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
Progression-Free Survival (PFS)	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)	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.
Percentage of Participants Who Died	Up to 5 years (from Baseline until death)	Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
Percentage of Participants With Death or Disease Progression	Up to 5 years (from Baseline until disease progression or death, whichever occurred first)	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.
Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)	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)	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.