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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FCR-lite | Experimental | Rituximab, fludarabine, and cyclophosphamide |
|
| LR Therapy | Active Comparator | Rituximab and chlorambucile |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chlorambucil | Drug | 10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles |
| |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The order of Honour pin Irkutsk regional clinical hospital; Hematology Department | Irkutsk | 664079 | Russia | |||
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| ID | Title | Description |
|---|---|---|
| FG000 | FCR-lite | Rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 (one cycle = 28 days), then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. When fludarabine / cyclophosphamide IV administered: fludarabine 20 mg/m^2 IV on Days 1-3; cyclophosphamide 150 mg/m^2 IV on Days 1-3. When fludarabine / cyclophosphamide orally administered: fludarabine 32 mg/m^2 orally on Days 1-3; cyclophosphamide 150 mg/m^2 orally on Days 1-3 for 6 cycles (28 days each). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Cyclophosphamide |
| Drug |
150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles |
|
| Fludarabine | Drug | 20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles |
|
| Rituximab | Drug | 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles) |
|
|
| 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 |
| Kemerovo Regional Clinical Hospital |
| Kemerovo |
| 650066 |
| Russia |
| N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis | Moscow | 115478 | Russia |
| City Clinical Botkin's Hospital; City Hematological Center | Moscow | 125284 | Russia |
| Saint-Petersburg SHI City Clinical Hospital #31 | Saint Petersburg | 197110 | Russia |
| City Clinical Hospital #15; Hematology department | Saint Petersburg | 198205 | Russia |
| GUZ Tula Regioanal Clinical Hospital; Hematology | Tula | 300053 | Russia |
| Republican clinical hospital named after G.G. Kuvatov | Ufa | 450005 | Russia |
| FG001 | LR Therapy | Rituximab 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. Chlorambucile 10 mg/m^2 orally on Days 1-7 for 6 cycles. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | FCR-lite | Rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 (one cycle = 28 days), then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. When fludarabine / cyclophosphamide IV administered: fludarabine 20 mg/m^2 IV on Days 1-3; cyclophosphamide 150 mg/m^2 IV on Days 1-3. When fludarabine / cyclophosphamide orally administered: fludarabine 32 mg/m^2 orally on Days 1-3; cyclophosphamide 150 mg/m^2 orally on Days 1-3 for 6 cycles (28 days each). |
| BG001 | LR Therapy | Rituximab 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. Chlorambucile 10 mg/m^2 orally on Days 1-7 for 6 cycles. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Complete Remission | Complete remission was defined as the disappearance of all signs of disease. | All enrolled participants who were evaluable for this outcome measure at the end of therapy. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
|
| |||||||||||||||||||||||||||||
| Primary | Percentage of Participants With Disease Progression | Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. | All enrolled participants who were evaluable for this outcome measure at the end of therapy. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
| ||||||||||||||||||||||||||||||
| Primary | Percentage of Participants With Stable Disease | Stable disease was defined as not meeting the criteria for partial remission or disease progression | All enrolled participants who were evaluable for this outcome measure at the end of therapy. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
| ||||||||||||||||||||||||||||||
| Primary | Percentage of Participants With Partial Remission | Partial remission was defined as a reduction in tumor size by >50%. | All enrolled participants who were evaluable for this outcome measure at the end of therapy. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
| ||||||||||||||||||||||||||||||
| Primary | 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%. | Enrolled participants who had disease progression after response to therapy. | Posted | Median | 95% Confidence Interval | days | Up to approximately 5 years |
| ||||||||||||||||||||||||||||||
| Primary | 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. | Enrolled participants who had disease progression at the end of the study. | Posted | Median | 95% Confidence Interval | days | Up to approximately 5 years |
|
| |||||||||||||||||||||||||||||
| Primary | 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%. | Enrolled participants who had an event of disease progression, relapse, or death. | Posted | Median | 95% Confidence Interval | days | Up to approximately 5 years |
| ||||||||||||||||||||||||||||||
| Primary | Overall Survival | Overall survival was defined as the time period from the first day of study treatment to participant death. | Enrolled participants who died. | Posted | Median | 95% Confidence Interval | days | Up to approximately 5 years |
|
| |||||||||||||||||||||||||||||
| Primary | 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. | Enrolled participants who were evaluable for this assessment. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
| ||||||||||||||||||||||||||||||
| Primary | 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. | All enrolled participants. | Posted | Number | percentage of participants | Up to approximately 5 years |
|
Up to approximately 5 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FCR-lite | Rituximab 375 milligrams per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 (one cycle = 28 days), then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. When fludarabine / cyclophosphamide IV administered: fludarabine 20 mg/m^2 IV on Days 1-3; cyclophosphamide 150 mg/m^2 IV on Days 1-3. When fludarabine / cyclophosphamide orally administered: fludarabine 32 mg/m^2 orally on Days 1-3; cyclophosphamide 150 mg/m^2 orally on Days 1-3 for 6 cycles (28 days each). | 2 | 10 | 8 | 10 | ||
| EG001 | LR Therapy | Rituximab 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. Chlorambucile 10 mg/m^2 orally on Days 1-7 for 6 cycles. | 3 | 16 | 9 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Retroperitoneal abscess | Infections and infestations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Vascular disorders | MedDRA, version 18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA, version 18.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Glomerular filtration rate | Investigations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Urea urine increased | Investigations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Sinusitis | Respiratory, thoracic and mediastinal disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Hyperglycaemia | Endocrine disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA, version 18.1 | Systematic Assessment |
| |
| Chills | Musculoskeletal and connective tissue disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA, version 18.1 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA, version 18.1 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 1-800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002699 | Chlorambucil |
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010752 | Phosphoramide Mustards |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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| Male |
|
|
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|
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| Units | Counts |
|---|---|
| Participants |
|
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| Participants |
|
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Rituximab 375 mg/m^2 IV on Day 1 of Cycle 1, then 500 mg/m^2 IV on Day 1 of each subsequent cycle for 6 cycles. Chlorambucile 10 mg/m^2 orally on Days 1-7 for 6 cycles.
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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