Trial Outcomes & Findings for A Study of Participant Preference With Subcutaneous Versus Intravenous MabThera/Rituxan in Participants With CD20+ Diffuse Large B-Cell Lymphoma or CD20+ Follicular Non-Hodgkin's Lymphoma Grades 1, 2 or 3a (NCT NCT01724021)

Last Updated: 2018-01-23

Results Overview

Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing cycle 6.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

743 participants

Primary outcome timeframe

Cycle 6 (Up to 24 weeks)

Results posted on

2018-01-23

Participant Flow

A total of 743 participants were enrolled across all the sites and were included in the intent to treat (ITT) population. Three participants were enrolled but died prior to receiving study medication and were not included in the safety population. The Participant Flow represents the safety population.

Participant milestones

Participant milestones
Measure	Arm A Participants in Arm A received one cycle of rituximab 375 milligram per metre square (mg/m\^2) intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Overall Study STARTED	371	369
Overall Study COMPLETED	244	236
Overall Study NOT COMPLETED	127	133

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Participants in Arm A received one cycle of rituximab 375 milligram per metre square (mg/m\^2) intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Overall Study Adverse Event	11	6
Overall Study Death	46	58
Overall Study Participant request/ Withdrew consent	18	14
Overall Study Lost to Follow-up	15	15
Overall Study Reason Not Specified	36	39
Overall Study Missing	1	1

Baseline Characteristics

A Study of Participant Preference With Subcutaneous Versus Intravenous MabThera/Rituxan in Participants With CD20+ Diffuse Large B-Cell Lymphoma or CD20+ Follicular Non-Hodgkin's Lymphoma Grades 1, 2 or 3a

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=371 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Total n=740 Participants Total of all reporting groups
Age, Continuous	58.2 years STANDARD_DEVIATION 13.18 • n=5 Participants	59.4 years STANDARD_DEVIATION 12.64 • n=7 Participants	58.8 years STANDARD_DEVIATION 12.92 • n=5 Participants
Sex: Female, Male Female	187 Participants n=5 Participants	180 Participants n=7 Participants	367 Participants n=5 Participants
Sex: Female, Male Male	184 Participants n=5 Participants	189 Participants n=7 Participants	373 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 6 (Up to 24 weeks)

Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6	79.1 percentage of participants Interval 74.2 to 83.5	80.6 percentage of participants Interval 75.7 to 84.8

PRIMARY outcome

Timeframe: Cycle 8 (Up to 32 weeks)

Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8	77.1 percentage of participants Interval 71.9 to 81.8	84.2 percentage of participants Interval 79.6 to 88.2

SECONDARY outcome

Timeframe: Randomization of first participant to clinical cutoff date (Up to 4 years)

Population: The safety population included all participants who received at least one dose of rituximab. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Outcome measures
Measure	Arm A n=371 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Number of Participants With Treatment Emergent Adverse Events (AEs)	352 participants	347 participants

SECONDARY outcome

Timeframe: Cycle 1-4, Cycle 5-8 for both SC and IV (Up to 32 weeks)

Population: ITT population included all participants who were randomized in the study.

Administration time was defined as the time from start to end of the SC injection or from start to end of the IV infusion

Outcome measures

Outcome measures
Measure	Arm A n=740 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=687 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV])	840 minutes Interval 0.0 to 3967.0	22 minutes Interval 0.0 to 1242.0

SECONDARY outcome

Timeframe: During Cycle 4, 8 of treatment (Up to 32 weeks)

Population: ITT population included all participants who were randomized in the study. Here, "Number Analyzed" represents the number of participants who were evaluable at specified time points.

CTSQ is a validated 16-item questionnaire that measures three domains related to participants' satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.

Outcome measures

Outcome measures
Measure	Arm A n=740 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=687 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Cancer Therapy Satisfaction Questionnaire (CTSQ) Score Expectations of therapy domain	80.88 units on a scale Standard Deviation 18.315	82.07 units on a scale Standard Deviation 17.817
Cancer Therapy Satisfaction Questionnaire (CTSQ) Score Feelings about side effects domain	60.63 units on a scale Standard Deviation 22.316	61.64 units on a scale Standard Deviation 22.324
Cancer Therapy Satisfaction Questionnaire (CTSQ) Score Satisfaction with therapy domain	84.59 units on a scale Standard Deviation 12.218	85.42 units on a scale Standard Deviation 11.259

SECONDARY outcome

Timeframe: During Cycle 4, 8 of treatment (Up to 32 weeks)

Population: ITT population included all participants who were randomized in the study. Here, "Number Analyzed" represents the number of participants who were evaluable at specified time points.

The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.

Outcome measures

Outcome measures
Measure	Arm A n=740 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=687 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Rituximab Administration Satisfaction Questionnaire (RASQ) Score Physical impact domain	82.14 units on a scale Standard Deviation 15.629	82.08 units on a scale Standard Deviation 15.882
Rituximab Administration Satisfaction Questionnaire (RASQ) Score Psychological Impact domain	77.73 units on a scale Standard Deviation 16.377	84.00 units on a scale Standard Deviation 14.358
Rituximab Administration Satisfaction Questionnaire (RASQ) Score Impact on activitiesf daily living	59.49 units on a scale Standard Deviation 22.233	81.86 units on a scale Standard Deviation 15.844
Rituximab Administration Satisfaction Questionnaire (RASQ) Score Convenience domain	59.05 units on a scale Standard Deviation 20.757	81.05 units on a scale Standard Deviation 13.088
Rituximab Administration Satisfaction Questionnaire (RASQ) Score Satisfaction domain	74.88 units on a scale Standard Deviation 19.349	87.26 units on a scale Standard Deviation 14.972

SECONDARY outcome

Timeframe: 28 days (± 3 days) after Day 1 of the last dose of induction treatment

Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.

CR rate was assessed according to the International Working Group (IWG) Response Criteria (CHESON ET AL. 1999) and included CR and CR unconfirmed (CRu). CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by \> 75 % but still \>1.5 cm in size, and indeterminate bone marrow assessment. Tumor assessments were based on computed tomography (CT) scans with contrast of the neck, chest, and abdomen (if detectable by these techniques) or other diagnostic means, if applicable. Other methods (e.g., MRI) were acceptable for participants in whom contrast CT scans were contraindicated. Due to the limited availability of FDG-PET scanners, an FDG-PET scan was not mandated in the study.

Outcome measures

Outcome measures
Measure	Arm A n=307 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=315 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Complete Response (CR) Rate	49.2 percentage of participants Interval 43.5 to 54.9	52.7 percentage of participants Interval 47.0 to 58.3

SECONDARY outcome

Timeframe: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)

Population: ITT population included all participants who were randomized in the study.

EFS was defined as the time from randomization to first occurrence of progression or relapse according to IWG response criteria. IWG criteria is defined using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; partial response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; stable disease (SD): participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease (PD); PD: Lymph nodes considered abnormal if the long axis is more than 1.5 centimeter (cm) regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes less than or equal to (\<=) 1.0 × \<= 1.0 cm would not be considered as abnormal for PD.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Event-free Survival (EFS)	NA months Median (and it's CI) was not reached for this Outcome Measure.	NA months Median (and it's CI) was not reached for this Outcome Measure.

SECONDARY outcome

Timeframe: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)

Population: ITT population included all participants who were randomized in the study.

DFS was defined as the period from the data of the initial CR/CRu until the date of relapse or death from any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Disease-free Survival (DFS)	NA months Median (and it's CI) was not reached for this Outcome Measure.	NA months Median (and it's CI) was not reached for this Outcome Measure.

SECONDARY outcome

Timeframe: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)

Population: ITT population included all participants who were randomized in the study.

PFS was defined as the time from randomization to the first occurrence of progression or relapse, according to the IWG response criteria. IWG criteria is defined criteria using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; PR: At least a 50% decrease in SPD of up to six of the largest dominant nodes or nodal masses; SD: participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD; PD: Lymph nodes considered abnormal if the long axis is more than 1.5 cm regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes \<= 1.0 × \<= 1.0 cm would not be considered as abnormal for PD.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Progression-free Survival (PFS)	NA months Median (and it's CI) was not reached for this Outcome Measure.	NA months Median (and it's CI) was not reached for this Outcome Measure.

SECONDARY outcome

Timeframe: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)

Population: ITT population included all participants who were randomized in the study.

OS was defined as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Arm A n=372 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=371 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Overall Survival (OS)	NA months Median (and it's CI) was not reached for this Outcome Measure.	NA months Median (and it's CI) was not reached for this Outcome Measure.

SECONDARY outcome

Timeframe: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)

Population: The safety population included all participants who received at least one dose of rituximab. Here, "Number Analyzed" represents the number of participants who were evaluable at specified time points.

Outcome measures

Outcome measures
Measure	Arm A n=371 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 1	2.0 percentage of participants	3.0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 2	2.1 percentage of participants	2.2 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 3	0.3 percentage of participants	0.9 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 4	0 percentage of participants	0.3 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Interim staging	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 5	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 6	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 7	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Cycle 8	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Final staging	0 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Follow-up, 6 months	1.8 percentage of participants	0 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time Follow-up, 12 months	2.1 percentage of participants	0.6 percentage of participants
Percentage of Participants With Anti-Rituximab Antibodies Over Time End of study/early treatment termination	0.6 percentage of participants	0.6 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)

Outcome measures

Outcome measures
Measure	Arm A n=371 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time End of study/early treatment termination	3.5 percentage of participants	6.3 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 1	11.4 percentage of participants	15.6 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 2	7.0 percentage of participants	18.2 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 3	7.1 percentage of participants	23.5 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 4	7.0 percentage of participants	14.7 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Interim staging	9.0 percentage of participants	9.7 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 5	12.5 percentage of participants	10.2 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 6	16.0 percentage of participants	11.6 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 7	23.8 percentage of participants	10.9 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Cycle 8	13.3 percentage of participants	11.0 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Final staging	10.0 percentage of participants	12.6 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Follow-up, 6 months	6.5 percentage of participants	13.4 percentage of participants
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time Follow-up, 12 months	7.7 percentage of participants	8.7 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)

Outcome measures

Outcome measures
Measure	Arm A n=371 Participants Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 Participants Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Summary of Observed Serum Rituximab Concentration Cycle 1	3355.9 microgram per milliter Standard Deviation 21600.95	970.1 microgram per milliter Standard Deviation 9415.93
Summary of Observed Serum Rituximab Concentration Cycle 2	25053.1 microgram per milliter Standard Deviation 19590.17	24541.1 microgram per milliter Standard Deviation 18141.76
Summary of Observed Serum Rituximab Concentration Cycle 3	62977.0 microgram per milliter Standard Deviation 30037.98	46093.9 microgram per milliter Standard Deviation 31214.30
Summary of Observed Serum Rituximab Concentration Cycle 4	87956.6 microgram per milliter Standard Deviation 40441.84	59485.5 microgram per milliter Standard Deviation 29183.17
Summary of Observed Serum Rituximab Concentration Interim staging	117273.6 microgram per milliter Standard Deviation 52227.06	77665.3 microgram per milliter Standard Deviation 29161.77
Summary of Observed Serum Rituximab Concentration Cycle 5	108030.9 microgram per milliter Standard Deviation 54335.08	70387.3 microgram per milliter Standard Deviation 30256.48
Summary of Observed Serum Rituximab Concentration Cycle 6	100927.7 microgram per milliter Standard Deviation 49287.42	98679.7 microgram per milliter Standard Deviation 40001.55
Summary of Observed Serum Rituximab Concentration Cycle 7	95614.0 microgram per milliter Standard Deviation 45499.56	117172.0 microgram per milliter Standard Deviation 44501.74
Summary of Observed Serum Rituximab Concentration Cycle 8	104873.0 microgram per milliter Standard Deviation 50346.69	137048.1 microgram per milliter Standard Deviation 53669.39
Summary of Observed Serum Rituximab Concentration Final staging	86806.6 microgram per milliter Standard Deviation 43005.90	120995.7 microgram per milliter Standard Deviation 58731.10
Summary of Observed Serum Rituximab Concentration Follow-up, 6 months	7802.9 microgram per milliter Standard Deviation 15672.57	8042.9 microgram per milliter Standard Deviation 12247.05
Summary of Observed Serum Rituximab Concentration Follow-up, 12 months	2380.1 microgram per milliter Standard Deviation 8494.06	1685.3 microgram per milliter Standard Deviation 6669.84
Summary of Observed Serum Rituximab Concentration End of study/early treatment termination	9302.0 microgram per milliter Standard Deviation 27234.88	9553.9 microgram per milliter Standard Deviation 30723.30

Adverse Events

Arm A

Serious events: 126 serious events

Other events: 318 other events

Deaths: 0 deaths

Arm B

Serious events: 116 serious events

Other events: 317 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm A n=371 participants at risk Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.	Arm B n=369 participants at risk Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator.
Gastrointestinal disorders Nausea	22.4% 83/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	27.6% 102/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Constipation	15.9% 59/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	16.3% 60/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Vomiting	11.9% 44/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	15.4% 57/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Diarrhoea	12.1% 45/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	13.6% 50/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Stomatitis	6.2% 23/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	6.2% 23/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Abdominal pain	6.2% 23/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	5.1% 19/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Gastrointestinal disorders Abdominal pain upper	4.6% 17/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	6.0% 22/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Blood and lymphatic system disorders Neutropenia	13.7% 51/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	19.0% 70/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Blood and lymphatic system disorders Anaemia	21.3% 79/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	18.4% 68/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Blood and lymphatic system disorders Leukopenia	10.2% 38/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	8.7% 32/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
General disorders Fatigue	18.6% 69/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	24.7% 91/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
General disorders Pyrexia	14.8% 55/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	13.0% 48/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
General disorders Mucosal inflammation	6.7% 25/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	7.0% 26/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
General disorders Chills	7.8% 29/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	4.1% 15/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Skin and subcutaneous tissue disorders Alopecia	16.2% 60/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	15.2% 56/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Skin and subcutaneous tissue disorders Pruritus	7.8% 29/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	4.6% 17/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Skin and subcutaneous tissue disorders Rash	5.1% 19/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	5.7% 21/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Nervous system disorders Neuropathy peripheral	10.0% 37/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	12.7% 47/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Nervous system disorders Headache	7.3% 27/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	7.9% 29/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Nervous system disorders Paraesthesia	4.9% 18/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	9.8% 36/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Respiratory, thoracic and mediastinal disorders Cough	12.1% 45/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	10.3% 38/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.4% 20/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	5.7% 21/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Infections and infestations Nasopharyngitis	5.4% 20/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	5.1% 19/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Infections and infestations Upper respiratory tract infection	5.9% 22/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	5.4% 20/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Investigations Neutrophil count decreased	17.0% 63/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	18.7% 69/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Investigations White blood cell count decreased	10.0% 37/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	8.9% 33/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Metabolism and nutrition disorders Decreased appetite	9.2% 34/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	8.7% 32/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
Psychiatric disorders Insomnia	6.7% 25/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	8.4% 31/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)
General disorders Oedema peripheral	4.6% 17/371 • Randomization of first participant to clinical cutoff date (Up to 4 years)	6.0% 22/369 • Randomization of first participant to clinical cutoff date (Up to 4 years)