A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

Study Overview
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Brief Summary
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This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Participants were randomized to receive Mabthera (375 mg/m2 intravenously [IV] Day 1 of Cycle 1, 500 mg/m2 IV Day 1 Cycles 2-6) with either fludarabine (20 mg/m2 IV or 32 mg/m2 orally Days 1-3) and cyclophosphamide (150 mg/m2 IV or orally Days 1-3) or with chlorambucil (10 mg/m2 orally Days 1-7) for 6 cycles of 28 days. Anticipated time on study treatment was 24 weeks.

Official Title
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Prospective Randomized Study to Compare Efficacy and Safety of RFC-Lite (Rituximab, Fludarabine, Cyclophosphamide) Regimen With LR (Rituximab, Chlorambucil) as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

Conditions
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Lymphocytic Leukemia, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, 60-70 or >70 years of age Cumulative Illness Rating Scale (CIRS) comorbidity score >/=7 if patient is 60-70 years old Previously untreated B-cell chronic lymphocytic leukemia Binet stage B, C or A with progression ECOG performance status 0-2 Exclusion Criteria: Small-cell lymphoma Autoimmune hemolytic anemia Concomitant malignant disease during enrollment, except for basal cell carcinoma of the skin Chemotherapy for concomitant malignant disease within 12 months prior to study enrollment Richter's syndrome

Ages Eligible for Study
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Minimum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCR-lite<br>Rituximab, fludarabine, and cyclophosphamide | Drug: Cyclophosphamide<br>* 150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles<br>Drug: Fludarabine<br>* 20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles<br>Drug: Rituximab<br>* 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles)<br>* Other names: MabThera;|
| Active Comparator: LR Therapy<br>Rituximab and chlorambucile | Drug: Chlorambucil<br>* 10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles<br>Drug: Rituximab<br>* 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles)<br>* Other names: MabThera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Remission | Complete remission was defined as the disappearance of all signs of disease. | Up to approximately 5 years | 
| Percentage of Participants With Disease Progression | Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. | Up to approximately 5 years | 
| Percentage of Participants With Stable Disease | Stable disease was defined as not meeting the criteria for partial remission or disease progression | Up to approximately 5 years | 
| Percentage of Participants With Partial Remission | Partial remission was defined as a reduction in tumor size by >50%. | Up to approximately 5 years | 
| Duration of Response | Duration of Response was defined as the time period from the last day of study treatment to the day when disease progression occurred in participants who previously had complete or partial remission. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%. | Up to approximately 5 years | 
| Progression-free Survival | Progression-free survival was defined as the time period from the first day of study treatment to the day when disease progression occurred. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. | Up to approximately 5 years | 
| Event-free Survival | Event-free survival was defined as the time period from the first day of study treatment to occurrence of any of the following events: appearance of disease progression or relapse; prescription of a new treatment for disease relapse; death caused by B-cell chronic lymphocytic leukemia (B-CLL); or complications from B-CLL or therapy. Relapse was defined as disease progression in participants with complete or partial remission lasting at least 6 months after treatment completion. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%. | Up to approximately 5 years | 
| Overall Survival | Overall survival was defined as the time period from the first day of study treatment to participant death. | Up to approximately 5 years | 
| Percentage of Participants With Phenotypic Remission | Phenotypic remission was considered achieved if a participant had a negative test for minimal residual disease. A negative test for minimal residual disease was defined as tumor cells ≤0.01% of the total number of peripheral leukocytes. | Up to approximately 5 years | 
| Percentage of Participants With Adverse Events (AEs) and Serious AEs | An AE was defined as any unfavorable medical occurrence in a participant receiving a study drug, regardless of relationship the study drug. An AE was considered serious if it met any of the following criteria: was fatal or life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was clinically significant and/or required an intervention to prevent any of the listed criteria. | Up to approximately 5 years |