A Study on Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01178086
• Collaborator: (none)
• Enrollment: 681
• Location: 1
• Actual Duration (Months): 64.2
• Patients Per Site Per Month: 10.6

Study Details

Study Description

Brief Summary

This observational study will assess the therapeutic efficiency, treatment schedules, handling procedures, and the safety profile of rituximab in routine care in participants with CLL.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Rituximab

Study Design

• Study Type: Observational
• Actual Enrollment: 681 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Rituximab in the Treatment of Chronic Lymphocytic Leukemia, "CLL NIS"
• Actual Study Start Date: Feb 22, 2010
• Actual Primary Completion Date: Jun 30, 2015
• Actual Study Completion Date: Jun 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Participants With CLL Participants with CLL who are being treated with intravenous (IV) rituximab in combination with chemotherapy, will be observed for 24 months including 6-month treatment period.	Drug: Rituximab; Rituximab IV; Other Names: MabThera

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) as Assessed Using Kaplan-Meier Estimate [From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)]

   PFS was defined as the time from initiation of treatment with rituximab in combination with chemotherapy to disease progression or death due to any cause, whichever occurred first. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (>/=) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes. Participants without disease progression or death at the time of analysis were censored at the last date of tumor evaluation in terms of PFS.

2. Percentage of Participants Without Progression or Death [From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)]

   Disease progression was defined as the occurrence of at least one of the following: >/=50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes.

Secondary Outcome Measures

1. Percentage of Participants With Progression and Death [From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)]

   Percentage of participants with an event (progression or death) was reported. Disease progression was defined as the occurrence of at least one of the following: >/=50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes.

2. Percentage of Participants Who Received Each Treatment During the Course of Study [Baseline, Cycle 1, 2, 3, 4, 5, 6, 7, 8, last Cycle (Cycle 18) (each cycle=1 month)]

   The chemotherapeutic regimen administereted during the course of study were: Rituximab-Bendamustine (R-Benda), Rituximab-Fludarabine-Cyclophosphamide (R-FC), Rituximab-Clorambucil (R-Clb), R-Other and Rituximab mono.

3. Mean Body Weight [Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)]

4. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status [Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)]

   ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair >50% of waking hours.

5. Percentage of Participants With Karnofsky Performance Status Index [Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)]

   Performance status was reflected by the Karnofsky index. Karnofsky performance status index ranges from 0-100% with higher scores indicating better functional status. An index between 90% and 100% corresponds to ECOG grade 0, index between 70% and 80% corresponds to ECOG grade 1, index between 50% and 60% corresponds to ECOG grade 2, index 40% corresponds to ECOG grade 3. ECOG grade 0=Fully active, able to carry on all pre-disease activities without restriction; grade 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; grade 2=Ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; grade 3=Capable of only limited self-care, confined to bed/chair >50% of waking hours.

6. Percentage of Participants With General Symptoms [Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)]

   General symptoms included fatigue, reduced performance, frequent infections, abdominal pain and exhaustion.

7. Percentage of Participants With B-Symptoms [Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)]

   B-symptoms included fever, night sweats, weight loss.

8. Percentage of Participants With Best Overall Response (BOR) [From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)]

   Response to treatment was assessed as per clinical routine. BOR included complete response(CR or CR with incomplete hematopoietic regeneration),partial response(PR or nodular PR),stable disease(SD),progressive disease(PD). CR:hemoglobin>/=11 grams/deciliter(g/dL), lymphocytes<4000 cells/cubic millimeter(cells/mm^3), neutrophils>5000 cells/mm^3,platelets>100,000 cells/mm^3,bone marrow biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, performance status of 0. PR:>50% decrease in size of enlarged lymph nodes, hepatomegaly, splenomegaly, with peripheral counts meeting same criteria as CR or >/=50% improvement from pre-treatment values.PD:occurrence of at least one of following: >/=50% increase in longest diameter of at least 2 enlarged lymph nodes, increase in spleen and liver size by at least 2 cm from Baseline, or >/=50% increase in number of circulating lymphocytes. Participants without CR/PR or PD were considered having SD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• CLL requiring treatment

• Participants receiving a chemotherapy in combination with rituximab (decision taken by doctor prior to and independent from inclusion in this non-interventional study)

• After this trial started, an amendment to the study protocol was introduced, adding a further inclusion criterion: Comorbidities according to cumulative illness rating scale (CIRS) score greater than (>) 6 and/or creatinine clearance less than (<) 70 milliliters per minute (mL/min)

Exclusion Criteria:

• Participants with contraindication to rituximab treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PIOH PD Dr. R. Schnell - Dr. H. Schulz - Dr. M. Hellmann	Frechen		Germany	50226

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: NCT01178086
• Other Study ID Numbers: ML22610
• First Posted: Aug 9, 2010
• Last Update Posted: Oct 5, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab

Study Results

Participant Flow

Pre-assignment Detail	This single arm study had baseline and analysis reported per 2 arms (Unselected Population and "Slow Go" Subpopulation).

Arm/Group Title	Participants With Chonic Lymphatic Leukemia (CLL)
Arm/Group Description	Participants with CLL who were treated with intravenous (IV) rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Period Title: Overall Study
STARTED	681
Effectiveness Analysis Set (EAS)	661
COMPLETED	349
NOT COMPLETED	332

Baseline Characteristics

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation	Total
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with cumulative illness rating scale for geriatrics [CIRS-G] score greater than [>] 6 and/or creatinine clearance less than [<] 70 milliliters per minute [mL/min]) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	Total of all reporting groups
Overall Participants	472	189	661
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.9 (9.0)	74.2 (7.9)	70.5 (9.0)
Sex: Female, Male (Count of Participants)
Female	160 33.9%	84 44.4%	244 36.9%
Male	312 66.1%	105 55.6%	417 63.1%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) as Assessed Using Kaplan-Meier Estimate
Description	PFS was defined as the time from initiation of treatment with rituximab in combination with chemotherapy to disease progression or death due to any cause, whichever occurred first. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (>/=) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes. Participants without disease progression or death at the time of analysis were censored at the last date of tumor evaluation in terms of PFS.
Time Frame	From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Median (95% Confidence Interval) [months]	50.6	33.7

2. Primary Outcome

Title	Percentage of Participants Without Progression or Death
Description	Disease progression was defined as the occurrence of at least one of the following: >/=50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes.
Time Frame	From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Number (95% Confidence Interval) [percentage of participants]	71.1 15.1%	62.7 33.2%

3. Secondary Outcome

Title	Percentage of Participants With Progression and Death
Description	Percentage of participants with an event (progression or death) was reported. Disease progression was defined as the occurrence of at least one of the following: >/=50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or >/=50% increase in the number of circulating lymphocytes.
Time Frame	From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS with events.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	106	51
Progression	68.9 14.6%	66.7 35.3%
Death	31.1 6.6%	33.3 17.6%

4. Secondary Outcome

Title	Percentage of Participants Who Received Each Treatment During the Course of Study
Description	The chemotherapeutic regimen administereted during the course of study were: Rituximab-Bendamustine (R-Benda), Rituximab-Fludarabine-Cyclophosphamide (R-FC), Rituximab-Clorambucil (R-Clb), R-Other and Rituximab mono.
Time Frame	Baseline, Cycle 1, 2, 3, 4, 5, 6, 7, 8, last Cycle (Cycle 18) (each cycle=1 month)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
R-Benda at Baseline	58.5 12.4%	64.0 33.9%
R-Benda at Cycle 1	56.8 12%	60.3 31.9%
R-Benda at Cycle 2	60.0 12.7%	67.8 35.9%
R-Benda at Cycle 3	58.8 12.5%	64.8 34.3%
R-Benda at Cycle 4	57.9 12.3%	62.3 33%
R-Benda at Cycle 5	56.5 12%	58.3 30.8%
R-Benda at Cycle 6	55.3 11.7%	60.6 32.1%
R-Benda at Cycle 7	44.7 9.5%	29.4 15.6%
R-Benda at Cycle 8	61.5 13%	10.0 5.3%
R-Benda at Last Cycle	55.7 11.8%	62.4 33%
R-FC at Baseline	23.3 4.9%	8.5 4.5%
R-FC at Cycle 1	22.0 4.7%	7.9 4.2%
R-FC at Cycle 2	24.0 5.1%	9.3 4.9%
R-FC at Cycle 3	23.5 5%	10.9 5.8%
R-FC at Cycle 4	24.4 5.2%	10.3 5.4%
R-FC at Cycle 5	23.4 5%	10.8 5.7%
R-FC at Cycle 6	23.4 5%	9.2 4.9%
R-FC at Cycle 7	10.5 2.2%	5.9 3.1%
R-FC at Cycle 8	3.8 0.8%	0.0 0%
R-FC at Last Cycle	23.7 5%	8.5 4.5%
R-Clb at Baseline	5.5 1.2%	11.1 5.9%
R-Clb at Cycle 1	5.5 1.2%	11.1 5.9%
R-Clb at Cycle 2	5.7 1.2%	9.8 5.2%
R-Clb at Cycle 3	5.8 1.2%	10.3 5.4%
R-Clb at Cycle 4	6.4 1.4%	11.0 5.8%
R-Clb at Cycle 5	6.4 1.4%	11.7 6.2%
R-Clb at Cycle 6	6.2 1.3%	12.8 6.8%
R-Clb at Cycle 7	5.3 1.1%	11.8 6.2%
R-Clb at Cycle 8	7.7 1.6%	20.0 10.6%
R-Clb at Last Cycle	5.5 1.2%	10.6 5.6%
R-Other at Baseline	9.7 2.1%	11.1 5.9%
R-Other at Cycle 1	9.5 2%	9.5 5%
R-Other at Cycle 2	9.3 2%	10.9 5.8%
R-Other at Cycle 3	9.0 1.9%	10.9 5.8%
R-Other at Cycle 4	8.3 1.8%	10.3 5.4%
R-Other at Cycle 5	8.8 1.9%	10.8 5.7%
R-Other at Cycle 6	8.6 1.8%	10.1 5.3%
R-Other at Cycle 7	10.5 2.2%	5.9 3.1%
R-Other at Cycle 8	0.0 0%	10.0 5.3%
R-Other at Last Cycle	8.9 1.9%	8.5 4.5%
Rituximab Mono at Baseline	0.0 0%	0.0 0%
Rituximab Mono at Cycle 1	0.0 0%	0.0 0%
Rituximab Mono at Cycle 2	0.7 0.1%	2.2 1.2%
Rituximab Mono at Cycle 3	2.4 0.5%	3.0 1.6%
Rituximab Mono at Cycle 4	2.4 0.5%	6.2 3.3%
Rituximab Mono at Cycle 5	4.6 1%	7.5 4%
Rituximab Mono at Cycle 6	6.2 1.3%	7.3 3.9%
Rituximab Mono at Cycle 7	28.9 6.1%	47.1 24.9%
Rituximab Mono at Cycle 8	26.9 5.7%	60.0 31.7%
Rituximab Mono at Last Cycle	5.7 1.2%	9.5 5%

5. Secondary Outcome

Title	Mean Body Weight
Time Frame	Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS. Overall number of participants analyzed=participants analyzed for this outcome. Here, number analyzed=participants evaluable at specified time-point.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	471	189
Baseline	77.4 (14.1)	75.0 (14.2)
Last Cycle	77.4 (15.2)	73.7 (13.9)
Last Visit	77.0 (15.3)	73.3 (14.2)

6. Secondary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Description	ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair >50% of waking hours.
Time Frame	Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS. Here, number analyzed=participants evaluable at specified time-point.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Grade 0 at Baseline	36.4 7.7%	23.8 12.6%
Grade 0 at Last Cycle	23.9 5.1%	19.0 10.1%
Grade 0 at Last Visit	34.0 7.2%	26.2 13.9%
Grade 1 at Baseline	40.5 8.6%	45.0 23.8%
Grade 1 at Last Cycle	33.5 7.1%	35.4 18.7%
Grade 1 at Last Visit	28.0 5.9%	22.1 11.7%
Grade 2 at Baseline	4.9 1%	6.3 3.3%
Grade 2 at Last Cycle	3.4 0.7%	4.8 2.5%
Grade 2 at Last Visit	3.8 0.8%	6.9 3.7%
Grade 3 at Baseline	0.4 0.1%	2.1 1.1%
Grade 3 at Last Cycle	1.3 0.3%	1.6 0.8%
Grade 3 at Last Visit	1.6 0.3%	2.1 1.1%
Missing at Baseline	17.8 3.8%	22.8 12.1%
Missing at Last Cycle	37.9 8%	39.2 20.7%
Missing at Last Visit	32.6 6.9%	42.8 22.6%

7. Secondary Outcome

Title	Percentage of Participants With Karnofsky Performance Status Index
Description	Performance status was reflected by the Karnofsky index. Karnofsky performance status index ranges from 0-100% with higher scores indicating better functional status. An index between 90% and 100% corresponds to ECOG grade 0, index between 70% and 80% corresponds to ECOG grade 1, index between 50% and 60% corresponds to ECOG grade 2, index 40% corresponds to ECOG grade 3. ECOG grade 0=Fully active, able to carry on all pre-disease activities without restriction; grade 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; grade 2=Ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; grade 3=Capable of only limited self-care, confined to bed/chair >50% of waking hours.
Time Frame	Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS. Here, number analyzed=participants evaluable at specified time-point.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Karnofsky index 100% at Baseline	25.4 5.4%	7.4 3.9%
Karnofsky index 100% at Last Cycle	14.8 3.1%	7.9 4.2%
Karnofsky index 100% at Last Visit	17.5 3.7%	11.0 5.8%
Karnofsky index 90% at Baseline	24.4 5.2%	25.4 13.4%
Karnofsky index 90% at Last Cycle	17.4 3.7%	18.5 9.8%
Karnofsky index 90% at Last Visit	14.6 3.1%	11.7 6.2%
Karnofsky index 80% at Baseline	14.2 3%	16.9 8.9%
Karnofsky index 80% at Last Cycle	7.4 1.6%	8.5 4.5%
Karnofsky index 80% at Last Visit	7.3 1.5%	9.0 4.8%
Karnofsky index 70% at Baseline	3.4 0.7%	5.8 3.1%
Karnofsky index 70% at Last Cycle	3.0 0.6%	4.2 2.2%
Karnofsky index 70% at Last Visit	2.4 0.5%	2.8 1.5%
Karnofsky index 60% at Baseline	0.6 0.1%	1.1 0.6%
Karnofsky index 60% at Last Cycle	0.2 0%	1.6 0.8%
Karnofsky index 60% at Last Visit	0.3 0.1%	0.7 0.4%
Karnofsky index 50% at Baseline	0.2 0%	0.0 0%
Karnofsky index 50% at Last Cycle	0.2 0%	0.0 0%
Karnofsky index 50% at Last Visit	0.3 0.1%	0.7 0.4%
Karnofsky index 40% at Baseline	0.0 0%	0.0 0%
Karnofsky index 40% at Last Cycle	0.0 0%	0.0 0%
Karnofsky index 40% at Last Visit	0.0 0%	0.0 0%
Missing at Baseline	31.8 6.7%	43.4 23%
Missing at Last Cycle	57.0 12.1%	59.3 31.4%
Missing at Last Visit	57.7 12.2%	64.1 33.9%

8. Secondary Outcome

Title	Percentage of Participants With General Symptoms
Description	General symptoms included fatigue, reduced performance, frequent infections, abdominal pain and exhaustion.
Time Frame	Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS. Here, number analyzed=participants evaluable at specified time-point.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Fatigue at Baseline	38.1 8.1%	45.0 23.8%
Fatigue at Last Cycle	23.5 5%	22.8 12.1%
Fatigue at Last Visit	17.8 3.8%	14.5 7.7%
Reduced Performance at Baseline	46.0 9.7%	49.2 26%
Reduced Performance at Last Cycle	24.2 5.1%	20.6 10.9%
Reduced Performance at Last Visit	21.3 4.5%	22.1 11.7%
Frequent Infections at Baseline	13.8 2.9%	15.9 8.4%
Frequent Infections at Last Cycle	5.5 1.2%	4.2 2.2%
Frequent Infections at Last Visit	7.5 1.6%	6.9 3.7%
Abdominal Pain at Baseline	8.3 1.8%	7.9 4.2%
Abdominal Pain at Last Cycle	1.9 0.4%	3.2 1.7%
Abdominal Pain at Last Visit	4.9 1%	2.8 1.5%
Exhaustion at Baseline	35.8 7.6%	40.2 21.3%
Exhaustion at Last Cycle	19.5 4.1%	15.9 8.4%
Exhaustion at Last Visit	14.6 3.1%	17.2 9.1%

9. Secondary Outcome

Title	Percentage of Participants With B-Symptoms
Description	B-symptoms included fever, night sweats, weight loss.
Time Frame	Baseline, last cycle (Cycle 18) (each cycle=1 month), last visit (follow-up) (24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS. Here, number analyzed=participants evaluable at specified time-point.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
Fever at Baseline	4.0 0.8%	4.8 2.5%
Fever at Last Cycle	3.4 0.7%	2.6 1.4%
Fever at Last Visit	2.2 0.5%	0.7 0.4%
Night Sweats at Baseline	29.0 6.1%	25.4 13.4%
Night Sweats at Last Cycle	3.2 0.7%	2.6 1.4%
Night Sweats at Last Visit	7.0 1.5%	6.9 3.7%
Weight Loss at Baseline	21.8 4.6%	21.2 11.2%
Weight Loss at Last Cycle	4.2 0.9%	3.7 2%
Weight Loss at Last Visit	5.7 1.2%	4.1 2.2%

10. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR)
Description	Response to treatment was assessed as per clinical routine. BOR included complete response(CR or CR with incomplete hematopoietic regeneration),partial response(PR or nodular PR),stable disease(SD),progressive disease(PD). CR:hemoglobin>/=11 grams/deciliter(g/dL), lymphocytes<4000 cells/cubic millimeter(cells/mm^3), neutrophils>5000 cells/mm^3,platelets>100,000 cells/mm^3,bone marrow biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, performance status of 0. PR:>50% decrease in size of enlarged lymph nodes, hepatomegaly, splenomegaly, with peripheral counts meeting same criteria as CR or >/=50% improvement from pre-treatment values.PD:occurrence of at least one of following: >/=50% increase in longest diameter of at least 2 enlarged lymph nodes, increase in spleen and liver size by at least 2 cm from Baseline, or >/=50% increase in number of circulating lymphocytes. Participants without CR/PR or PD were considered having SD.
Time Frame	From initiation of treatment up to disease progression or death due to any cause, whichever occurred first (assessed up to 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on EAS.

Arm/Group Title	Unselected Population (Participants With Any Comorbidity)	"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.	"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
Measure Participants	472	189
CR	37.9 8%	32.8 17.4%
PR	37.3 7.9%	39.2 20.7%
SD	8.1 1.7%	8.5 4.5%
PD	2.8 0.6%	2.1 1.1%
Not assessable	4.9 1%	5.3 2.8%
Not assessed / Missing	9.1 1.9%	12.2 6.5%

Adverse Events

Time Frame	Baseline up to 24 months
Adverse Event Reporting Description	Analysis was performed on safety analysis set.
Arm/Group Title	Unselected Population (Participants With Any Comorbidity)		"Slow Go" Subpopulation
Arm/Group Description	Unselected population (participants with any comorbidity) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.		"Slow go" subpopulation (participants with CIRS-G score >6 and/or creatinine clearance <70 mL/min) who were treated with IV rituximab in combination with chemotherapy, were observed for 24 months including 6-month treatment period.
All Cause Mortality
	Unselected Population (Participants With Any Comorbidity)		"Slow Go" Subpopulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Unselected Population (Participants With Any Comorbidity)		"Slow Go" Subpopulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/485 (17.5%)		44/196 (22.4%)
Blood and lymphatic system disorders
Anemia	5/485 (1%)		6/196 (3.1%)
Autoimmune hemolytic anemia	1/485 (0.2%)		0/196 (0%)
Bone marrow toxicity	1/485 (0.2%)		0/196 (0%)
Cytopenia	1/485 (0.2%)		0/196 (0%)
Febrile neutropenia	5/485 (1%)		1/196 (0.5%)
Leukopenia	11/485 (2.3%)		5/196 (2.6%)
Neutropenia	17/485 (3.5%)		5/196 (2.6%)
Pancytopenia	1/485 (0.2%)		0/196 (0%)
Thrombocytopenia	8/485 (1.6%)		2/196 (1%)
Hematotoxicity	0/485 (0%)		1/196 (0.5%)
Cardiac disorders
Acute myocardial infarction	1/485 (0.2%)		0/196 (0%)
Arrhythmia	1/485 (0.2%)		0/196 (0%)
Cardiac disorder	1/485 (0.2%)		0/196 (0%)
Cardiac failure	1/485 (0.2%)		0/196 (0%)
Atrial fibrillation	0/485 (0%)		1/196 (0.5%)
Endocrine disorders
Adrenal mass	1/485 (0.2%)		0/196 (0%)
Gastrointestinal disorders
Abdominal pain upper	2/485 (0.4%)		1/196 (0.5%)
Diarrhoea	1/485 (0.2%)		0/196 (0%)
Gastrointestinal hemorrhage	2/485 (0.4%)		0/196 (0%)
Ileus	1/485 (0.2%)		0/196 (0%)
Melena	1/485 (0.2%)		0/196 (0%)
Mouth hemorrhage	1/485 (0.2%)		0/196 (0%)
Nausea	1/485 (0.2%)		1/196 (0.5%)
Vomiting	3/485 (0.6%)		0/196 (0%)
Pancreatitis acute	0/485 (0%)		1/196 (0.5%)
General disorders
Asthenia	1/485 (0.2%)		0/196 (0%)
Chills	4/485 (0.8%)		1/196 (0.5%)
Death	1/485 (0.2%)		0/196 (0%)
Disease progression	2/485 (0.4%)		1/196 (0.5%)
Effusion	1/485 (0.2%)		0/196 (0%)
General physical health deterioration	5/485 (1%)		3/196 (1.5%)
Pyrexia	13/485 (2.7%)		1/196 (0.5%)
Immune system disorders
Hypersensitivity	2/485 (0.4%)		2/196 (1%)
Secondary immunodeficiency	1/485 (0.2%)		1/196 (0.5%)
Infections and infestations
Atypical Pneumonia	1/485 (0.2%)		0/196 (0%)
Bacterial infection	10/485 (2.1%)		3/196 (1.5%)
Bronchitis	2/485 (0.4%)		0/196 (0%)
Device related infection	1/485 (0.2%)		0/196 (0%)
Fungal infection	1/485 (0.2%)		0/196 (0%)
Herpes zoster	3/485 (0.6%)		0/196 (0%)
Klebsiella bacteraemia	1/485 (0.2%)		0/196 (0%)
Meningitis	1/485 (0.2%)		0/196 (0%)
Necrotizing fasciitis	1/485 (0.2%)		0/196 (0%)
Pneumonia viral	1/485 (0.2%)		0/196 (0%)
Sepsis	3/485 (0.6%)		3/196 (1.5%)
Staphylococcal sepsis	1/485 (0.2%)		0/196 (0%)
Viral infection	1/485 (0.2%)		0/196 (0%)
Endocarditis	0/485 (0%)		2/196 (1%)
Enterococcal infection	0/485 (0%)		1/196 (0.5%)
Febrile infection	0/485 (0%)		1/196 (0.5%)
Infection	0/485 (0%)		1/196 (0.5%)
Pneumonia	0/485 (0%)		3/196 (1.5%)
Septic shock	0/485 (0%)		1/196 (0.5%)
Upper respiratory tract infection	0/485 (0%)		1/196 (0.5%)
Urinary tract infection	0/485 (0%)		1/196 (0.5%)
Injury, poisoning and procedural complications
Injury	1/485 (0.2%)		0/196 (0%)
Splenic rupture	1/485 (0.2%)		0/196 (0%)
Ankle fracture	0/485 (0%)		1/196 (0.5%)
Fall	0/485 (0%)		3/196 (1.5%)
Femur fracture	0/485 (0%)		1/196 (0.5%)
Toxicity to various agents	0/485 (0%)		1/196 (0.5%)
Investigations
Blood pressure increased	1/485 (0.2%)		0/196 (0%)
Body temperature increased	1/485 (0.2%)		0/196 (0%)
White blood cell count increased	1/485 (0.2%)		0/196 (0%)
Hemoglobin decreased	0/485 (0%)		2/196 (1%)
Metabolism and nutrition disorders
Hypoglycaemia	1/485 (0.2%)		0/196 (0%)
Tumour lysis syndrome	1/485 (0.2%)		0/196 (0%)
Dehydration	0/485 (0%)		1/196 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/485 (0.2%)		0/196 (0%)
Muscle spasms	0/485 (0%)		1/196 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/485 (0.2%)		0/196 (0%)
Malignant melanoma	1/485 (0.2%)		0/196 (0%)
Malignant neoplasm progression	4/485 (0.8%)		0/196 (0%)
Metastases to bone	1/485 (0.2%)		0/196 (0%)
Metastases to liver	1/485 (0.2%)		0/196 (0%)
Metastases to lung	1/485 (0.2%)		0/196 (0%)
Metastatic neoplasm	1/485 (0.2%)		0/196 (0%)
Rectal cancer	1/485 (0.2%)		0/196 (0%)
Small cell lung cancer	1/485 (0.2%)		0/196 (0%)
Lymphatic system neoplasm	0/485 (0%)		1/196 (0.5%)
Nervous system disorders
Cerebrovascular accident	1/485 (0.2%)		0/196 (0%)
Depressed level of consciousness	1/485 (0.2%)		0/196 (0%)
Dizziness	1/485 (0.2%)		0/196 (0%)
Syncope	1/485 (0.2%)		1/196 (0.5%)
Epilepsy	0/485 (0%)		1/196 (0.5%)
Paraesthesia	0/485 (0%)		1/196 (0.5%)
Peroneal nerve palsy	0/485 (0%)		1/196 (0.5%)
Presyncope	0/485 (0%)		1/196 (0.5%)
Seizure	0/485 (0%)		1/196 (0.5%)
Renal and urinary disorders
Chronic kidney disease	1/485 (0.2%)		0/196 (0%)
Hematuria	1/485 (0.2%)		0/196 (0%)
Acute kidney injury	0/485 (0%)		1/196 (0.5%)
Renal failure	0/485 (0%)		1/196 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/485 (0.4%)		1/196 (0.5%)
Lung infiltration	1/485 (0.2%)		0/196 (0%)
Pleural effusion	2/485 (0.4%)		1/196 (0.5%)
Pulmonary embolism	1/485 (0.2%)		1/196 (0.5%)
Respiratory failure	0/485 (0%)		1/196 (0.5%)
Skin and subcutaneous tissue disorders
Drug eruption	1/485 (0.2%)		0/196 (0%)
Swelling face	1/485 (0.2%)		0/196 (0%)
Rash	0/485 (0%)		1/196 (0.5%)
Rash pruritic	0/485 (0%)		1/196 (0.5%)
Surgical and medical procedures
Dental operation	1/485 (0.2%)		0/196 (0%)
Hospitalization	0/485 (0%)		1/196 (0.5%)
Vascular disorders
Circulatory collapse	1/485 (0.2%)		0/196 (0%)
Embolism	1/485 (0.2%)		0/196 (0%)
Haematoma	1/485 (0.2%)		0/196 (0%)
Hot flush	1/485 (0.2%)		0/196 (0%)
Thrombosis	1/485 (0.2%)		0/196 (0%)
Deep vein thrombosis	0/485 (0%)		1/196 (0.5%)
Hypertensive crisis	0/485 (0%)		1/196 (0.5%)
Other (Not Including Serious) Adverse Events
	Unselected Population (Participants With Any Comorbidity)		"Slow Go" Subpopulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	259/485 (53.4%)		98/196 (50%)
Blood and lymphatic system disorders
Anemia	40/485 (8.2%)		21/196 (10.7%)
Leukopenia	129/485 (26.6%)		48/196 (24.5%)
Neutropenia	33/485 (6.8%)		15/196 (7.7%)
Thrombocytopenia	99/485 (20.4%)		31/196 (15.8%)
Gastrointestinal disorders
Diarrhoea	26/485 (5.4%)		14/196 (7.1%)
Nausea	67/485 (13.8%)		20/196 (10.2%)
General disorders
Chills	38/485 (7.8%)		17/196 (8.7%)
Pyrexia	46/485 (9.5%)		15/196 (7.7%)
Fatigue	0/485 (0%)		11/196 (5.6%)
Immune system disorders
Hypersensitivity	47/485 (9.7%)		19/196 (9.7%)
Infections and infestations
Bacterial infection	29/485 (6%)		0/196 (0%)

Limitations/Caveats

[Not Specified]

More Information

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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.