A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status

Study Overview
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Brief Summary
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This multi-center, single-arm study evaluated the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide in participants with B-cell chronic lymphocytic leukemia (CLL) and favorable somatic status.

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

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: Diagnosis of previously untreated B-cell CLL confirmed immunophenotypically For participants, age 60-70 years: Cumulative Illness Rating Scale (CIRS) comorbidity score less than or equal to (</=) 6 Binet stage B, C or A with progression Life expectancy greater than or equal to (>/=) 12 months Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 Women of child bearing potential and men should agree to use highly reliable contraceptive method throughout the treatment period and within 12 months after treatment completion Exclusion Criteria: Participants with small-cell lymphoma Participants with auto-immune hemolytic anemia Concomitant malignant disease during enrollment, except basal cell carcinoma of the skin Chemotherapy for concomitant malignant disease given within 12 months prior to study enrollment Participants with Richter's Syndrome Participants with symptomatic Hepatitis B infection Any clinically significant infection that could not be cured prior to enrollment, including Human Immunodeficiency Virus (HIV) infection Creatinine clearance less than (<) 30 milliliters per minute (mL/min) Participants with congestive heart failure (CHF) New York Heart Association (NYHA) III-IV Participants with liver failure and acute hepatitis of any etiology Any other medical or mental condition which may preclude from receiving the entire course of protocol specified treatment or signing the informed consent History of an anaphylactic reaction to murine antibodies, proteins, or any other ingredient of rituximab Pregnancy and breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 received rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m^2 IV or 40 mg/m^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m^2 IV or 250 mg/m^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each. | Drug: Cyclophosphamide<br>* Participants received cyclophosphamide 250 mg/m^2 IV or 250 mg/m^2 orally on Days 1-3 of each cycle.<br>Drug: Fludarabine<br>* Participants received fludarabine 25 mg/m^2 IV or 40 mg/m^2 orally on Days 1-3 of each cycle.<br>Drug: Rituximab<br>* Participants received 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle.<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 |