A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status
- Conditions
- Lymphocytic Leukemia, Chronic
- Interventions
- Registration Number
- NCT01271010
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 89
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rituximab + Fludarabine + Cyclophosphamide Cyclophosphamide 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. Rituximab + Fludarabine + Cyclophosphamide Fludarabine 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. Rituximab + Fludarabine + Cyclophosphamide Rituximab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete Remission Up to approximately 5 years Complete remission was defined as the disappearance of all signs of disease.
Percentage of Participants With Disease Progression 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 Stable Disease Up to approximately 5 years Stable disease was defined as not meeting the criteria for partial remission or disease progression
Percentage of Participants With Partial Remission Up to approximately 5 years Partial remission was defined as a reduction in tumor size by \>50%.
Duration of Response 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%.
Overall Survival 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 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.
Progression-free Survival 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.
Event-free Survival 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 Phenotypic Remission 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (10)
Regional Clinical Oncology Despensary #1; Hematology Department
🇷🇺Krasnodar, Russian Federation
The order of Honour pin Irkutsk regional clinical hospital; Hematology Department
🇷🇺Irkutsk, Russian Federation
Kemerovo Regional Clinical Hospital
🇷🇺Kemerovo, Russian Federation
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
🇷🇺Moscow, Russian Federation
City Clinical Hospital #15; Hematology department
🇷🇺Saint-Petersburg, Russian Federation
GUZ Tula Regioanal Clinical Hospital; Hematology
🇷🇺Tula, Russian Federation
Republican clinical hospital named after G.G. Kuvatov
🇷🇺UFA, Russian Federation
Leningrad Regional Clinical Hospital; Hematology #1
🇷🇺St Petersburg, Russian Federation
Saint-Petersburg SHI City Clinical Hospital #31
🇷🇺St. Petersburg, Russian Federation
City Clinical Hospital After Botkin; Hematology
🇷🇺Moscow, Russian Federation