A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01283386
• Collaborator: (none)
• Enrollment: 26
• Locations: 8
• Arms: 2
• Actual Duration (Months): 58.6
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Chlorambucil; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 27, 2011
• Actual Primary Completion Date: Mar 16, 2016
• Actual Study Completion Date: Mar 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FCR-lite Rituximab, fludarabine, and cyclophosphamide	Drug: Cyclophosphamide; 150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles; Drug: Fludarabine; 20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles; Drug: Rituximab; 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles); Other Names: MabThera
Active Comparator: LR Therapy Rituximab and chlorambucile	Drug: Chlorambucil; 10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles; Drug: Rituximab; 375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles); Other Names: MabThera

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Remission [Up to approximately 5 years]

   Complete remission was defined as the disappearance of all signs of disease.

2. 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.

3. 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

4. Percentage of Participants With Partial Remission [Up to approximately 5 years]

   Partial remission was defined as a reduction in tumor size by >50%.

5. 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%.

6. 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.

7. 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%.

8. 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.

9. 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.

10. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The order of Honour pin Irkutsk regional clinical hospital; Hematology Department	Irkutsk		Russian Federation	664079
2	Kemerovo Regional Clinical Hospital	Kemerovo		Russian Federation	650066
3	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow		Russian Federation	115478
4	City Clinical Botkin's Hospital; City Hematological Center	Moscow		Russian Federation	125284
5	City Clinical Hospital #15; Hematology department	Saint-Petersburg		Russian Federation	198205
6	Saint-Petersburg SHI City Clinical Hospital #31	St. Petersburg		Russian Federation	197110
7	GUZ Tula Regioanal Clinical Hospital; Hematology	Tula		Russian Federation	300053
8	Republican clinical hospital named after G.G. Kuvatov	UFA		Russian Federation	450005

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01283386
• Other Study ID Numbers: ML25137
• First Posted: Jan 26, 2011
• Last Update Posted: Mar 14, 2019
• Last Verified: Nov 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Cyclophosphamide; Chlorambucil; Rituximab; Fludarabine

Study Results

Participant Flow

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Period Title: Overall Study
STARTED	10	16
COMPLETED	2	4
NOT COMPLETED	8	12

Baseline Characteristics

Arm/Group Title	FCR-lite	LR Therapy	Total
Arm/Group Description	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).	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.	Total of all reporting groups
Overall Participants	10	16	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.7 (7.09)	68.6 (4.95)	68.6 (5.73)
Sex: Female, Male (Count of Participants)
Female	3 30%	7 43.8%	10 38.5%
Male	7 70%	9 56.3%	16 61.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All enrolled participants who were evaluable for this outcome measure at the end of therapy.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	7	16
Number [percentage of participants]	42.9 429%	18.8 117.5%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All enrolled participants who were evaluable for this outcome measure at the end of therapy.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	7	16
Number [percentage of participants]	0 0%	6.3 39.4%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All enrolled participants who were evaluable for this outcome measure at the end of therapy.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	7	16
Number [percentage of participants]	14.3 143%	18.8 117.5%

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All enrolled participants who were evaluable for this outcome measure at the end of therapy.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	7	16
Number [percentage of participants]	42.9 429%	56.3 351.9%

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who had disease progression after response to therapy.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	5	12
Median (95% Confidence Interval) [days]	NA	NA

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who had disease progression at the end of the study.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	8	16
Median (95% Confidence Interval) [days]	NA	NA

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who had an event of disease progression, relapse, or death.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	9	16
Median (95% Confidence Interval) [days]	679	NA

8. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who died.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	10	16
Median (95% Confidence Interval) [days]	NA	NA

9. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Enrolled participants who were evaluable for this assessment.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	8	10
Number [percentage of participants]	25.0 250%	30.0 187.5%

10. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	FCR-lite	LR Therapy
Arm/Group Description	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).	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.
Measure Participants	10	16
Non-serious AEs	80.00 800%	56.25 351.6%
Serious AEs	20.00 200%	18.75 117.2%

Adverse Events

Time Frame	Up to approximately 5 years
Arm/Group Title	FCR-lite		LR Therapy
Arm/Group Description	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).		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.
All Cause Mortality
	FCR-lite		LR Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FCR-lite		LR Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		3/16 (18.8%)
General disorders
Death	2/10 (20%)		0/16 (0%)
Infections and infestations
Retroperitoneal abscess	0/10 (0%)		1/16 (6.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/10 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/10 (0%)		1/16 (6.3%)
Vascular disorders
Acute myocardial infarction	1/10 (10%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	FCR-lite		LR Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		9/16 (56.3%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)		1/16 (6.3%)
Thrombocytopenia	1/10 (10%)		0/16 (0%)
Cardiac disorders
Angina unstable	0/10 (0%)		1/16 (6.3%)
Cardiac failure acute	1/10 (10%)		0/16 (0%)
Extrasystoles	0/10 (0%)		1/16 (6.3%)
Endocrine disorders
Hyperglycaemia	0/10 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Nausea	1/10 (10%)		0/16 (0%)
General disorders
Pyrexia	2/10 (20%)		0/16 (0%)
Infections and infestations
Respiratory tract infection	0/10 (0%)		1/16 (6.3%)
Investigations
Neutrophil count decreased	2/10 (20%)		2/16 (12.5%)
White blood cell count decreased	1/10 (10%)		2/16 (12.5%)
Blood bilirubin increased	1/10 (10%)		0/16 (0%)
Glomerular filtration rate	1/10 (10%)		0/16 (0%)
Urea urine increased	0/10 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Chills	0/10 (0%)		1/16 (6.3%)
Renal and urinary disorders
Renal colic	1/10 (10%)		0/16 (0%)
Reproductive system and breast disorders
Prostatitis	1/10 (10%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	2/10 (20%)		1/16 (6.3%)
Pneumonia	0/10 (0%)		1/16 (6.3%)
Sinusitis	0/10 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.