Back to resultsA Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status
Primary Purpose
Lymphocytic Leukemia, Chronic
Status
Terminated
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphocytic Leukemia, Chronic
Eligibility Criteria
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
Sites / Locations
- The order of Honour pin Irkutsk regional clinical hospital; Hematology Department
- Kemerovo Regional Clinical Hospital
- Regional Clinical Oncology Despensary #1; Hematology Department
- N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
- City Clinical Hospital After Botkin; Hematology
- City Clinical Hospital #15; Hematology department
- Leningrad Regional Clinical Hospital; Hematology #1
- Saint-Petersburg SHI City Clinical Hospital #31
- GUZ Tula Regioanal Clinical Hospital; Hematology
- Republican clinical hospital named after G.G. Kuvatov
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab + Fludarabine + Cyclophosphamide
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Complete Remission
Complete remission was defined as the disappearance of all signs of disease.
Percentage of Participants With Disease Progression
Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Percentage of Participants With Stable Disease
Stable disease was defined as not meeting the criteria for partial remission or disease progression
Percentage of Participants With Partial Remission
Partial remission was defined as a reduction in tumor size by >50%.
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%.
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.
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%.
Overall Survival
Overall survival was defined as the time period from the first day of study treatment to participant death.
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.
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01271010
Brief Title
A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Study Start Date
June 17, 2011 (Actual)
Primary Completion Date
May 4, 2016 (Actual)
Study Completion Date
May 4, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphocytic Leukemia, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab + Fludarabine + Cyclophosphamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Participants received cyclophosphamide 250 mg/m^2 IV or 250 mg/m^2 orally on Days 1-3 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Participants received fludarabine 25 mg/m^2 IV or 40 mg/m^2 orally on Days 1-3 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Remission
Description
Complete remission was defined as the disappearance of all signs of disease.
Time Frame
Up to approximately 5 years
Title
Percentage of Participants With Disease Progression
Description
Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Time Frame
Up to approximately 5 years
Title
Percentage of Participants With Stable Disease
Description
Stable disease was defined as not meeting the criteria for partial remission or disease progression
Time Frame
Up to approximately 5 years
Title
Percentage of Participants With Partial Remission
Description
Partial remission was defined as a reduction in tumor size by >50%.
Time Frame
Up to approximately 5 years
Title
Duration of Response
Description
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%.
Time Frame
Up to approximately 5 years
Title
Progression-free Survival
Description
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.
Time Frame
Up to approximately 5 years
Title
Event-free Survival
Description
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%.
Time Frame
Up to approximately 5 years
Title
Overall Survival
Description
Overall survival was defined as the time period from the first day of study treatment to participant death.
Time Frame
Up to approximately 5 years
Title
Percentage of Participants With Phenotypic Remission
Description
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.
Time Frame
Up to approximately 5 years
Title
Percentage of Participants With Adverse Events (AEs) and Serious AEs
Description
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.
Time Frame
Up to approximately 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
The order of Honour pin Irkutsk regional clinical hospital; Hematology Department
City
Irkutsk
ZIP/Postal Code
664079
Country
Russian Federation
Facility Name
Kemerovo Regional Clinical Hospital
City
Kemerovo
ZIP/Postal Code
650066
Country
Russian Federation
Facility Name
Regional Clinical Oncology Despensary #1; Hematology Department
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
Facility Name
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
City Clinical Hospital After Botkin; Hematology
City
Moscow
ZIP/Postal Code
125101
Country
Russian Federation
Facility Name
City Clinical Hospital #15; Hematology department
City
Saint-Petersburg
ZIP/Postal Code
198205
Country
Russian Federation
Facility Name
Leningrad Regional Clinical Hospital; Hematology #1
City
St Petersburg
Country
Russian Federation
Facility Name
Saint-Petersburg SHI City Clinical Hospital #31
City
St. Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
Facility Name
GUZ Tula Regioanal Clinical Hospital; Hematology
City
Tula
ZIP/Postal Code
300053
Country
Russian Federation
Facility Name
Republican clinical hospital named after G.G. Kuvatov
City
UFA
ZIP/Postal Code
450005
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status
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