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
Overview
- Phase
- Phase 4
- Intervention
- Rituximab
- Conditions
- Lymphocytic Leukemia, Chronic
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 26
- Locations
- 8
- Primary Endpoint
- Event-free Survival
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
LR Therapy
Rituximab and chlorambucile
Intervention: Rituximab
FCR-lite
Rituximab, fludarabine, and cyclophosphamide
Intervention: Cyclophosphamide
FCR-lite
Rituximab, fludarabine, and cyclophosphamide
Intervention: Fludarabine
FCR-lite
Rituximab, fludarabine, and cyclophosphamide
Intervention: Rituximab
LR Therapy
Rituximab and chlorambucile
Intervention: Chlorambucil
Outcomes
Primary Outcomes
Event-free Survival
Time Frame: Up to approximately 5 years
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%.
Percentage of Participants With Complete Remission
Time Frame: Up to approximately 5 years
Complete remission was defined as the disappearance of all signs of disease.
Percentage of Participants With Stable Disease
Time Frame: Up to approximately 5 years
Stable disease was defined as not meeting the criteria for partial remission or disease progression
Duration of Response
Time Frame: Up to approximately 5 years
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%.
Progression-free Survival
Time Frame: Up to approximately 5 years
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.
Percentage of Participants With Disease Progression
Time Frame: Up to approximately 5 years
Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Percentage of Participants With Phenotypic Remission
Time Frame: Up to approximately 5 years
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.
Percentage of Participants With Partial Remission
Time Frame: Up to approximately 5 years
Partial remission was defined as a reduction in tumor size by \>50%.
Overall Survival
Time Frame: Up to approximately 5 years
Overall survival was defined as the time period from the first day of study treatment to participant death.
Percentage of Participants With Adverse Events (AEs) and Serious AEs
Time Frame: Up to approximately 5 years
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.