A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01200758

Collaborator

(none)

410

Enrollment

152

Locations

Arms

80.5

Actual Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This two-stage, multi-center, randomized, controlled, open-label study will investigate the pharmacokinetics, efficacy and safety of rituximab SC versus rituximab IV in participants with previously untreated follicular non-Hodgkin's lymphoma. Participants will be randomized to receive 375 milligrams per meter square (mg/m^2) rituximab as IV infusion or 1400 milligrams (mg) rituximab SC. In addition, participants will receive standard chemotherapy. Participants who achieved a complete or partial response (PR) after 8 treatment cycles, will receive maintenance treatment for a further maximum number of 12 cycles. Maintenance treatment cycles will be repeated every 8 weeks. This is a two-stage study. Stage 1 was designed to confirm the chosen rituximab SC dose resulting in comparable rituximab serum Ctrough levels compared with rituximab IV, when given as part of induction treatment every 3 weeks. Enrollment for Stage 2 started after the rituximab SC dose was established in Stage 1. Stage 2 aimed to further investigate the efficacy and safety of rituximab SC compared with rituximab IV. The anticipated time on study treatment is 96 weeks.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Rituximab SC Drug: Rituximab IV Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone/Prednisolone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Two-Stage Phase III, International, Multi-Center, Randomized, Controlled, Open-Label Study to Investigate the Pharmacokinetics, Efficacy and Safety of Rituximab SC in Combination With CHOP or CVP Versus Rituximab IV in Combination With CHOP or CVP in Patients With Previously Untreated Follicular Lymphoma Followed by Maintenance Treatment With Either Rituximab SC or Rituximab IV

Actual Study Start Date :

Feb 15, 2011

Actual Primary Completion Date :

Jun 12, 2012

Actual Study Completion Date :

Oct 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP) Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	Drug: Rituximab IV Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months. Other Names: MabThera Drug: Cyclophosphamide Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks. Drug: Doxorubicin Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks. Drug: Vincristine Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks. Drug: Prednisone/Prednisolone Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.
Experimental: Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP) First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.	Drug: Rituximab SC First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Other Names: MabThera Drug: Cyclophosphamide Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks. Drug: Doxorubicin Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks. Drug: Vincristine Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks. Drug: Prednisone/Prednisolone Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.

Arm

Intervention/Treatment

Active Comparator: Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)

Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.

Drug: Rituximab IV

Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.

Other Names:

MabThera

Drug: Cyclophosphamide

Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks.

Drug: Doxorubicin

Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks.

Drug: Vincristine

Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks.

Drug: Prednisone/Prednisolone

Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.

Experimental: Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)

First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.

Drug: Rituximab SC

First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.

Other Names:

MabThera

Drug: Cyclophosphamide

Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks.

Drug: Doxorubicin

Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks.

Drug: Vincristine

Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks.

Drug: Prednisone/Prednisolone

Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.

Outcome Measures

Primary Outcome Measures

Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab [Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks)]
Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL) [Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (≥) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.

Secondary Outcome Measures

Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Overall Response comprised CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in the SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Overall Response comprised of CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumour response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Complete Response was comprised CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)]
Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)]
Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL [Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)]
Overall Response comprised of CR, CRu, or PR . A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death [Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)]
Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL [Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)]
PFS was defined as the time from randomization to disease progression/relapse or death due to any cause. If the specified event (disease progression/relapse, death) did not occur, PFS was censored at the last tumor assessment date showing no disease progression, either during treatment or follow-up. Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. PFS analysis was performed using Kaplan - Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL [Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)]
Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL [Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)]
Event-free survival was defined as the time from randomization to disease progression/relapse, death or initiation of new NHL therapy. If the specified event (progression/relapse, death or new anti-lymphoma treatment) did not occur, event-free survival was censored at the last tumor assessment date either during treatment or follow up. Event-free survival analysis was performed using Kaplan-Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Percentage of Participants Who Died [Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])]
Overall Survival (OS) [Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])]
OS was defined as the time from randomization to death due to any cause. Participants without event were censored at the time of last follow-up information for survival, ie, at the last time known to be alive.
Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab [Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)]
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Predose (within 2 hr) and 24 hrs postdose on Cy 7 (D1,3,7,15), predose (0 hr) on Cy 8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy 7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab [Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)]
Predose (within 2 hr) and 24 hrs postdose on Cy7 (D1,3,7,15), predose (0 hr) on Cy8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle [Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description)]
Stage I and II (Induction): Rituximab IV: Predose (within 2 hr) on D1 of Cy1-8 (1 Cy=3 weeks & 4 weeks for Cy8); Rituximab SC: Predose (within 2 hr) on D1 of Cy1 & Cy3-8 (1 Cy=3 weeks and 4 weeks for Cy8), predose (within 2 hr) on D0 of Cy2 (up to data cutoff of 31 Oct 2013 [up to 32 months])
Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle [Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description)]
Stage I and II (maintenance): D29 of Cy8 (induction; 1 Cy=4 weeks), predose (within 2 hr) on D1 of Cy9 to 19 (maintenance Cy1 to 12 [1 Cy=8 weeks]; up to data cutoff of 11 Jan 2016 [up to 6 years])
Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration [12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years])]
Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase [Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2]
Depletion is defined as a cluster of differentiation (CD) 19 value <80 cells per cubic millimeter (cells/mm^3).
Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase [Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years])]
Depletion is defined as a CD19 value <80 cells/mm^3.
Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab [Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)]
Levels of HACA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab [Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)]
Levels of HAHA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20 [After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)]
All investigator physicians and nurses involved in this study were asked to provide the staff time that could be saved with each administration of rituximab SC as compared with rituximab IV to participants in routine practice afetr Cy 8, 15, 20 and categorized as less than (<) 1 hr, at least 1 hr but <2 hrs, at least 2 hrs but <3 hrs, at least 3 hrs but <4 hrs, >/=4 hrs. Staff were asked not to consider the time needed for the first IV administration. Analysis was done in all participants to show a comparison on the time saved by staffs when administered via SC and IV.
Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion [After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)]
All investigator physicians and nurses involved in this study were asked to complete question i.e. "Which formulation of rituximab (SC or IV) do you think is more convenient?" based on their experience with the rituximab SC and IV formulations across all participants and presented as rituximab SC is much more convenient; rituximab SC is a little more convenient; both formulations are equally convenient; rituximab IV is a little more convenient; and rituximab IV is much more convenient.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cluster of differentiation 20 (CD20)-positive, follicular Non-Hodgkin's lymphoma grade 1, 2, 3a. A tumor biopsy must have been performed within 6 months before study entry with material available for central review
No prior treatment
Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

Grade 3b follicular lymphoma
Transformation to high-grade lymphoma secondary to follicular lymphoma
Types of Non-Hodgkin's lymphoma other than follicular lymphoma
Presence or history of central nervous system (CNS) disease
Corticoid therapy during the last 4 weeks, except prednisone treatment less than (<) 20 milligrams per day (mg per day)
Known active bacterial, viral, fungal, or mycobacterial, or any major episode of infections requiring hospitalization or treatment with IV antibiotics within 4 weeks of start of study medication, or oral antibiotics within 2 weeks prior to start of study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gosford Hospital; Cancer Care Services	Gosford	New South Wales	Australia	2250
2	Wollongong Hospital; Cancer Services	Wollongong	New South Wales	Australia	2500
3	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
4	Gold Coast Hospital; Haematology Department	Southport	Queensland	Australia	4215
5	Queen Elizabeth Hospital; Haematology	Woodville South	South Australia	Australia	5011
6	UZ Antwerpen	Edegem		Belgium	2650
7	CHU Sart-Tilman	Liège		Belgium	4000
8	Sint Augustinus Wilrijk	Wilrijk		Belgium	2610
9	University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept	Banja Luka		Bosnia and Herzegovina	88000
10	University Clinical Center Sarajevo, Clinic for Hematology	Sarajevo		Bosnia and Herzegovina	71000
11	University Clinical Centre Tuzla, Clinic for Oncology, Hematology and Radiotherapy	Tuzla		Bosnia and Herzegovina	75000
12	Nucleo de Hematologia e Transplante de Medula Ossea de Minas Gerais	Belo Horizonte	MG	Brazil	30140-001
13	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-003
14	Hospital Sao Lucas - PUCRS	Porto Alegre	RS	Brazil	90610-000
15	Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia	Sao Paulo	SP	Brazil	01221-020
16	Hospital das Clinicas - FMUSP	Sao Paulo	SP	Brazil	05403-000
17	UMHAT Dr Georgi Stranski; Hematology	Pleven		Bulgaria	5800
18	Umhat S. George; Hematology	Plovdiv		Bulgaria	4002
19	Specialised Hospital For Treatment Of Hematological Diseases; Hematology	Sofia		Bulgaria	1756
20	Mhat Sveta Marina; Dept. of Haematology	Varna		Bulgaria	9010
21	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia	Canada	B3H 2Y9
22	Cite de La Sante de Laval; Hemato-Oncologie	Laval	Quebec	Canada	H7M 3L9
23	Centre de sante et de services sociaux Rimouski Neigette	Rimouski	Quebec	Canada	G5L 5T1
24	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
25	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec	Canada	G8Z 3R9
26	CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie	Quebec		Canada	G1J 1Z4
27	Fundacion Cardioinfantil	Bogota		Colombia
28	Centro Medico Imbanaco	Cali		Colombia
29	Hospital Pablo Tobon Uribe	Medellin-Antioquia		Colombia
30	Oncólogos de Occidente	Pereira		Colombia	600004
31	UHC Rijeka	Rijeka		Croatia	51000
32	University Hospital Center Zagreb; Haematology Department	Zagreb		Croatia	10000
33	Herlev Uni Hospital; Hæmatologisk Afdeling L 121	Herlev		Denmark	2730
34	Rigshospitalet; Hæmatologisk Klinik	København Ø		Denmark	2100
35	Odense Universitetshospital; Hæmatologisk Afdeling	Odense C		Denmark	5000
36	Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium	Roskilde		Denmark	4000
37	Vejle Hospital; Dept of Medicine, Division of Hematology	Vejle		Denmark	7100
38	Aarhus Universitetshospital, Hæmatologisk Afdeling R	Århus		Denmark	8000
39	Helsinki University Central Hospital; Dept of Oncology	Helsinki		Finland	00029
40	Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie	Bordeaux		France	33077
41	Hopital Henri Mondor; Hematologie Clinique	Creteil		France	94010
42	Chu Site Du Bocage;Hematologie Clinique	Dijon		France	21079
43	Clinique Victor Hugo; Chimiotherapie	Le Mans		France	72015
44	Institut J Paolii Calmettes; Onco Hematologie 1	Marseille		France	13273
45	Hopital Saint Eloi; Hematologie Oncologie Medicale	Montpellier		France	34295
46	Hopital Hotel Dieu Et Hme;Hopital De Jour	Nantes		France	44093
47	Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)	Paris		France	75475
48	Hopital De Haut Leveque; Hematologie Clinique	Pessac		France	33604
49	Ch Lyon Sud; Hemato Secteur Jules Courmont	Pierre Benite		France	69495
50	Hopital De La Miletrie; Hematologie Et Oncologie Medicale	Poitiers		France	86021
51	Hopital Bretonneau; Hematologie Therapie Cellulaire	Tours		France	37044
52	M.Zodelava's Hematology Center	Tbilisi		Georgia	0112
53	Mediclub	Tbilisi		Georgia	0160
54	Institute of Hematology and Transfusiology	Tbilisi		Georgia	0177
55	Chemotherapy and Immunotherapy Clinic Medulla	Tbilisi		Georgia	0186
56	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin		Germany	10707
57	Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie	Darmstadt		Germany	64283
58	Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin	Dresden		Germany	01307
59	PIOH PD Dr. R. Schnell - Dr. H. Schulz - Dr. M. Hellmann	Frechen		Germany	50226
60	Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I	Giessen		Germany	35392
61	Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik	Greifswald		Germany	17475
62	Internistisch-Onkologische Gemeinschaftspraxis; Dres. Rohrberg, Hurtz, Schma usw.	Halle		Germany	06110
63	Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover		Germany	30625
64	St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2	Karlsruhe		Germany	76137
65	UKSH Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie	Kiel		Germany	24105
66	Gemeinschaftspraxis PD Dr. med. Marcel Reiser und Dr. med. Ildiko Kátay	Koeln		Germany	50674
67	Onkologische Gemeinschaftspraxis	Magdeburg		Germany	39104
68	Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach	Marburg		Germany	35037
69	Medizinisches Versorgungszentrum MOP	München		Germany	80335
70	Praxis Dr.med. Jens Uhlig	Naunhof		Germany	04683
71	Praxis Dr. Clemens Müller-Naendrup (Onkologische Schwerpunktpraxis im MVZ 2 GmbH)	Olpe		Germany	57462
72	Prosper-Hospital, Medizinische Klinik I	Recklinghausen		Germany	45659
73	Praxis Dr. Fenchel	Saalfeld		Germany	07318
74	Caritas Kilinik St. Theresia; Abt. Innere Medizin	Saarbruecken		Germany	66113
75	Praxis für Hämatologie & Onkologie	Saarbruecken		Germany	66113
76	Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine	Athens		Greece	115 27
77	Attiko Hospital; Haematology Clinic	Athens		Greece	124 62
78	Azienda Ospedaliera Ospedale S.Carlo; Ematologia	Potenza	Basilicata	Italy	85100
79	A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica	Napoli	Campania	Italy	80131
80	AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia	Reggio Emilia	Emilia-Romagna	Italy	42100
81	Ospedale S. Eugenio; Divisione Di Ematologia	Roma	Lazio	Italy	00144
82	Uni Degli Studi Di Genova; 1A Divisione Di Ematologia	Genova	Liguria	Italy	16132
83	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia	Brescia	Lombardia	Italy	25123
84	Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia	Milano	Lombardia	Italy	20141
85	IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo	San Giovanni Rotondo	Puglia	Italy	71013
86	Ospedale Ca Foncello; Ematologia	Treviso	Veneto	Italy	31100
87	Ospedale Di Vicenza; Nefrologia, Ematologia	Vicenza	Veneto	Italy	36100
88	University Clinic for Hematology; HSCT Department	Skopje		Macedonia, The Former Yugoslav Republic of	1000
89	University Clinic of Hematology Skopje, Hospital Care Department	Skopje		Macedonia, The Former Yugoslav Republic of	1000
90	University Malaya Medical Center; Hematology Unit of Department of Internal Medicine	Kuala Lumpur	FED. Territory OF Kuala Lumpur	Malaysia	59100
91	Ampang Hospital; Department of Haematology	Ampang		Malaysia	68000
92	Sarawak General Hospital; Department of Radiotherapy, Oncology and Palliative care	Sarawak		Malaysia	93586
93	Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre	Chihuahua		Mexico	31000
94	Hospital General De Culiacan; Servicio De Hematologia	Culiacan		Mexico	80230
95	Hospital Universitario Dr. Jose E. Gonzalez; Haematology	Monterrey		Mexico	64460
96	Centro de Estudios Clinicos de Queretaro (CECLIQ)	Queretaro		Mexico	76000
97	Canterbury Health Laboratories; Haematology	Christchurch		New Zealand	8011
98	Palmerston North Hospital; Regional Cancer Treatment Service	Palmerston North		New Zealand	4442
99	Instituto;Oncologico Miraflores	Lima		Peru	18
100	Oncosalud Sac; Oncología	Lima		Peru	41
101	Hospital Maria Auxiliadora	Lima		Peru	Lima 29
102	Spitalul Clinic Judetean de Urgenta Brasov,Clinica de Hematologie	Brasov		Romania	500326
103	Fundeni Clinical Inst. ; Hematology Dept	Bucharest		Romania	022328
104	Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi, Clinica de Hematologie	Iasi		Romania	700111
105	Institutul Regional de Oncologie Iasi; Clinica de Hematologie	Iasi		Romania	700483
106	Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie	Targu-mures		Romania	540136
107	Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie	Timisoara		Romania	300079
108	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan		Russian Federation	420029
109	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow		Russian Federation	115478
110	Haematology Research Center; Haematology	Moscow		Russian Federation	125167
111	Penza Regional Oncology Dispensary	Penza		Russian Federation	440071
112	St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta	Saint-Petersburg		Russian Federation	197022
113	Research Inst. of Hematology & Blood Transfusion ; Hematology	St Petersburg		Russian Federation	191024
114	Russian Scientific Center of Radiology and Surgical Technologies; Dept of Radiology	St.Petersburg, Pesochny		Russian Federation	197758
115	Institute of Hematology	Belgrade		Serbia	11000
116	Clinical Center Vojvodine; Clinic for Hematology	Novi Sad		Serbia	21000
117	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore		Singapore	119228
118	Singapore General Hospital; Department of Haematology	Singapore		Singapore	169608
119	National Cancer Centre; Medical Oncology	Singapore		Singapore	169610
120	St. Elisabeths Cancer Center	Bratislava		Slovakia	812 50
121	National Cancer Inst. ; Dept. of Chemotherapy	Bratislava		Slovakia	833 10
122	National Hospital; Oncotherapy Dept	Bloemfontein		South Africa	9301
123	King Edward VIII; Department of Haematology	Congella		South Africa	4013
124	Durban Oncology Center	Durban		South Africa	4091
125	University of Witwatersrand/Johannesburg Hospital; Dept. of ocnology	Johannesburg		South Africa	2193
126	Cancercare	Kraaifontein		South Africa	7570
127	Hospital Universitario Puerta del Mar; Servicio de Hematologia	Cádiz	Cadiz	Spain	11009
128	Hospital del Mar; Servicio de Hematologia	Barcelona		Spain	08003
129	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona		Spain	08035
130	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
131	Hospital Duran i Reynals; Servicio de Hematologia	Barcelona		Spain	08907
132	Hospital Universitario de la Princesa; Servicio de Hematologia	Madrid		Spain	28006
133	Hospital Ramon y Cajal; Servicio de Hematologia	Madrid		Spain	28034
134	Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia	Murcia		Spain	30120
135	Hospital Clinico Universitario de Salamanca;Servicio de Hematologia	Salamanca		Spain	37007
136	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla		Spain	41013
137	Hospital Universitario la Fe; Servicio de Oncologia	Valencia		Spain	46026
138	National Cancer Inst.	Bangkok		Thailand	10400
139	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10700
140	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen		Thailand	40002
141	Adana Baskent University Hospital; Medical Oncology	Adana		Turkey	01120
142	Istanbul University Cerrahpasa Medical Faculty; Hematology Department	Istanbul		Turkey	34098
143	Bilim University School of Medicine; Hematology	Istanbul		Turkey	34394
144	Dokuz Eylul Uni ; Hematology	Izmir		Turkey	35100
145	Ege Uni Medical School; Hematology	Izmir		Turkey	35100
146	Ninewells Hospital & Medical School; Ward 34	Dundee		United Kingdom	DD1 9SY
147	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone		United Kingdom	ME16 9QQ
148	Derriford Hospital; Department of Haematology	Plymouth		United Kingdom	PL6 8DH
149	Queen's Hospital; Oncology	Romford		United Kingdom	RM7 0AG
150	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
151	Pinderfields General Hospital; Dept of Haematology	Wakefield		United Kingdom	WF1 4DG
152	New Cross Hospital; Dept. Of Haematology	Wolverhampton		United Kingdom	WV10 0QP

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:

NCT01200758

Other Study ID Numbers:

BO22334
2010-021377-36

First Posted:

Sep 14, 2010

Last Update Posted:

Nov 27, 2018

Last Verified:

Oct 1, 2018

Additional relevant MeSH terms:

Lymphoma

Lymphoma, Non-Hodgkin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Screening/baseline tests were performed within 28 days before randomization. Randomization was centralized in a 1:1 fashion using the Pocock and Simon dynamic randomization algorithm. The study was conducted in 2 stages: Stage I & II. All participants irrespective of the treatment period completion commenced follow-up period in both Stage I and II.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)	Stage II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab intravenous (IV) infusion (375 milligrams per square meter [mg/m^2]; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least partial response (PR) during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 milligrams [mg]; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Period Title: Stage I
STARTED	64	63	0	0
COMPLETED	46	46	0	0
NOT COMPLETED	18	17	0	0
Period Title: Stage I
STARTED	0	0	141	142
COMPLETED	0	0	100	92
NOT COMPLETED	0	0	41	50

Baseline Characteristics

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)	Total
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.	Total of all reporting groups
Overall Participants	205	205	410
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (12.69)	56.1 (12.66)	56.5 (12.67)
Sex: Female, Male (Count of Participants)
Female	99 48.3%	120 58.5%	219 53.4%
Male	106 51.7%	85 41.5%	191 46.6%

Outcome Measures

1. Primary Outcome

Title	Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab
Description
Time Frame	Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
Stage I pharmacokinetic (PK) evaluable population comprised all participants with data for Ctrough available at Cycle 7 and/or observed area under the serum concentration-time curve (AUC) available at Cycle 7. Participants were analyzed as per treatment received. Number of participants analyzed = participants analyzed for this outcome measure.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	48	54
Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliter (mcg/mL)]	83.1 (36.7)	134.6 (43.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferior Ctrough in SC formulation was demonstrated, if the lower bound of 90% confidence interval (CI) was above 0.8.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 90% 1.36 to 1.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio adjusted for tumor load at baseline.

2. Primary Outcome

Title	Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL)
Description	Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (≥) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
Stage II ITT Population included all participants who were randomized in Stage II irrespective whether they received study drug or not.

Arm/Group Title	Stage II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	141	142
Number (95% Confidence Interval) [percentage of participants]	85.1 41.5%	80.3 39.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2835
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-4.82
	Confidence Interval	(2-Sided) 95% -14.0 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.38 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Overall Response comprised CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in the SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
Stage I ITT Population included all participants who were randomized in Stage I irrespective whether they received study drug or not.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	64	63
Number (95% Confidence Interval) [percentage of participants]	82.8 40.4%	90.5 44.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2047
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	7.66
	Confidence Interval	(2-Sided) 95% -5.0 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.97
	Confidence Interval	(2-Sided) 95% 0.68 to 5.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Overall Response comprised of CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumour response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD; PR: ≥50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Number (95% Confidence Interval) [percentage of participants]	84.9 41.4%	84.4 41.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8911
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95% -7.7 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.56 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Complete Response was comprised CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
Stage I ITT Population.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	64	63
Number (95% Confidence Interval) [percentage of participants]	25.0 12.2%	42.9 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0335
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in CRR
	Estimated Value	17.86
	Confidence Interval	(2-Sided) 95% 0.8 to 35.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.25
	Confidence Interval	(2-Sided) 95% 1.06 to 4.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
Stage II ITT Population.

Arm/Group Title	Stage II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	141	142
Number (95% Confidence Interval) [percentage of participants]	34.8 17%	28.2 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2331
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-6.58
	Confidence Interval	(2-Sided) 95% -17.8 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% 0.44 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Number (95% Confidence Interval) [percentage of participants]	31.7 15.5%	32.2 15.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9157
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95% -8.8 to 9.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95% 0.66 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)

Outcome Measure Data

Analysis Population Description
ITT population; only participants who entered the maintenance phase and received at least 1 cycle of rituximab maintenance treatment from Cycle 9 to Cycle 20 were included in the analysis.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	178	172
Number (95% Confidence Interval) [percentage of participants]	57.9 28.2%	50.6 24.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1715
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-7.28
	Confidence Interval	(2-Sided) 95% -18.0 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.52 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL
Description	Overall Response comprised of CR, CRu, or PR . A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.
Time Frame	Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)

Outcome Measure Data

Analysis Population Description
ITT population; only participants who entered the maintenance phase and received at least 1 cycle of rituximab maintenance treatment from Cycle 9 to Cycle 20 were included in the analysis.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	178	172
Number (95% Confidence Interval) [percentage of participants]	78.1 38.1%	77.9 38%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9671
	Comments
	Method	Chi-squared
	Comments

Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -9.2 to 8.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% CI for the difference in response rates was estimated using the Hauck-Anderson method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% 0.60 to 1.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death
Description	Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Number [percentage of participants]	34.6 16.9%	31.7 15.5%

11. Secondary Outcome

Title	Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL
Description	PFS was defined as the time from randomization to disease progression/relapse or death due to any cause. If the specified event (disease progression/relapse, death) did not occur, PFS was censored at the last tumor assessment date showing no disease progression, either during treatment or follow-up. Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. PFS analysis was performed using Kaplan - Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT Population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Median (95% Confidence Interval) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5526
	Comments
	Method	Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.64 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL
Description	Disease progression: ≥50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or ≥50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Number [percentage of participants]	36.1 17.6%	35.1 17.1%

13. Secondary Outcome

Title	Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL
Description	Event-free survival was defined as the time from randomization to disease progression/relapse, death or initiation of new NHL therapy. If the specified event (progression/relapse, death or new anti-lymphoma treatment) did not occur, event-free survival was censored at the last tumor assessment date either during treatment or follow up. Event-free survival analysis was performed using Kaplan-Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])
Time Frame	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Median (95% Confidence Interval) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9115
	Comments
	Method	Wald test
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.71 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants Who Died
Description
Time Frame	Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])

Outcome Measure Data

Analysis Population Description
ITT population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Number [percentage of participants]	12.7 6.2%	8.8 4.3%

15. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause. Participants without event were censored at the time of last follow-up information for survival, ie, at the last time known to be alive.
Time Frame	Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])

Outcome Measure Data

Analysis Population Description
ITT population.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	205	205
Median (95% Confidence Interval) [days]	NA	NA

16. Secondary Outcome

Title	Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab
Description	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Predose (within 2 hr) and 24 hrs postdose on Cy 7 (D1,3,7,15), predose (0 hr) on Cy 8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy 7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Time Frame	Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
Stage I PK evaluable population. Here, number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	58	55
Geometric Mean (Geometric Coefficient of Variation) [mcg*day/mL]	2734.21 (32.51)	3778.93 (37.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments	The ratio of observed rituximab serum was determined as AUC SC/AUC IV during Cycle 7 of induction treatment.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 90% 1.24 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab
Description	Predose (within 2 hr) and 24 hrs postdose on Cy7 (D1,3,7,15), predose (0 hr) on Cy8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])
Time Frame	Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
Stage 1 PK Evaluable Population. Here, number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle of rituximab IV (375 mg/m^2) + 7 cycles of rituximab subcutaneously (SC) (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	58	59
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	250.63 (19.66)	236.82 (31.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Stage I: Rituximab IV + Chemotherapy (CHOP/CVP), Stage I: Rituximab SC + Chemotherapy (CHOP/CVP)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	0.941
	Confidence Interval	(2-Sided) 95% 0.872 to 1.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle
Description	Stage I and II (Induction): Rituximab IV: Predose (within 2 hr) on D1 of Cy1-8 (1 Cy=3 weeks & 4 weeks for Cy8); Rituximab SC: Predose (within 2 hr) on D1 of Cy1 & Cy3-8 (1 Cy=3 weeks and 4 weeks for Cy8), predose (within 2 hr) on D0 of Cy2 (up to data cutoff of 31 Oct 2013 [up to 32 months])
Time Frame	Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	198	193
Cycle 1 (n = 198, 193)	14.00 (157.53)	12.88 (189.70)
Cycle 2 (n = 197, 190)	30.13 (145.36)	40.00 (124.50)
Cycle 3 (n = 192, 190)	45.25 (110.35)	63.83 (101.83)
Cycle 4 (n = 186, 185)	54.06 (108.90)	81.71 (92.28)
Cycle 5 (n = 185, 185)	64.68 (89.90)	98.00 (71.91)
Cycle 6 (n = 187, 180)	71.02 (87.60)	109.56 (58.74)
Cycle 7 (n = 183, 172)	78.31 (77.76)	120.75 (55.60)
Cycle 8 (n = 52, 54)	77.60 (70.53)	131.48 (50.20)

19. Secondary Outcome

Title	Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle
Description	Stage I and II (maintenance): D29 of Cy8 (induction; 1 Cy=4 weeks), predose (within 2 hr) on D1 of Cy9 to 19 (maintenance Cy1 to 12 [1 Cy=8 weeks]; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame	Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	174	170
Cycle 8 (n = 174, 170)	37.69 (94.30)	61.31 (65.52)
Cycle 9 (n = 171, 168)	30.35 (75.03)	49.47 (81.23)
Cycle 10 (n = 164, 160)	28.44 (84.64)	47.27 (73.03)
Cycle 11 (n = 164, 157)	28.77 (65.28)	46.70 (66.80)
Cycle 12 (n = 160, 150)	28.80 (56.97)	44.72 (68.74)
Cycle 13 (n = 157, 150)	28.84 (54.04)	44.32 (67.67)
Cycle 14 (n = 153, 147)	28.09 (55.61)	43.32 (67.97)
Cycle 15 (n = 148, 143)	28.19 (52.69)	44.11 (67.92)
Cycle 16 (n = 150, 145)	28.05 (57.19)	42.96 (64.32)
Cycle 17 (n = 149, 143)	28.24 (57.51)	42.82 (65.67)
Cycle 18 (n = 143, 132)	28.59 (62.06)	44.79 (68.56)
Cycle 19 (n = 138, 131)	27.75 (78.26)	43.69 (69.02)

20. Secondary Outcome

Title	Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration
Description
Time Frame	12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years])

Outcome Measure Data

Analysis Population Description
Safety Analysis Population included all participants who received at least one dose of rituximab, either IV or SC. Participants were analyzed as treated. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	117	118
Week 12: Follow-up Visit 1 (n = 117, 118)	15.60	22.35
Week 24: Follow-up Visit 2 (n = 88, 96)	2.89	5.19
Week 36: Follow-up Visit 3 (n = 38, 53)	1.08	2.02

21. Secondary Outcome

Title	Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase
Description	Depletion is defined as a cluster of differentiation (CD) 19 value <80 cells per cubic millimeter (cells/mm^3).
Time Frame	Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	188	180
Cycle 1 Day 1 - Baseline (n=188, 168)	51.6 25.2%	54.8 26.7%
Cycle 2 Day 0 (n=183, 180)	95.1 46.4%	95.0 46.3%
Cycle 3 Day 1 (n=175, 175)	99.4 48.5%	99.4 48.5%
Cycle 4 Day 1 (n=178, 180)	99.4 48.5%	100.0 48.8%
Cycle 5 Day 1 (n=179, 176)	100.0 48.8%	100.0 48.8%
Cycle 6 Day 1 (n=173, 175)	100.0 48.8%	100.0 48.8%
Cycle 7 Day 1 (n=178, 173)	100.0 48.8%	100.0 48.8%
Cycle 8 Day 1 (n=175, 174)	100.0 48.8%	100.0 48.8%

22. Secondary Outcome

Title	Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase
Description	Depletion is defined as a CD19 value <80 cells/mm^3.
Time Frame	Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years])

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	170	164
Cycle 9 Day 1 (n=170, 161)	99.4 48.5%	100.0 48.8%
Cycle 10 Day 1 (n=165, 164)	99.4 48.5%	100.0 48.8%
Cycle 11 Day 1 (n=158, 158)	99.4 48.5%	100.0 48.8%
Cycle 12 Day 1 (n=151, 146)	100.0 48.8%	100.0 48.8%
Cycle 13 Day 1 (n=149, 143)	100.0 48.8%	100.0 48.8%
Cycle 14 Day 1 (n=152, 143)	100.0 48.8%	100.0 48.8%
Cycle 15 Day 1 (n=149, 140)	100.0 48.8%	100.0 48.8%
Cycle 16 Day 1 (n=142, 141)	100.0 48.8%	100.0 48.8%
Cycle 17 Day 1 (n=145, 142)	100.0 48.8%	100.0 48.8%
Cycle 18 Day 1 (n=141, 140)	100.0 48.8%	100.0 48.8%
Cycle 19 Day 1 (n=140, 138)	100.0 48.8%	100.0 48.8%
Cycle 20 Day 1 (n=139, 134)	100.0 48.8%	100.0 48.8%

23. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Description	Levels of HACA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame	Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
Safety Analysis Population: included 6 participants who were randomized under Rituximab SC arm but withdrew after Cy1 and then analyzed under Rituximab IV arm. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	208	197
Baseline (n=208, 191)	5.8 2.8%	2.6 1.3%
Post-Baseline (n=206, 197)	1.5 0.7%	2.0 1%

24. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab
Description	Levels of HAHA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])
Time Frame	Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)

Outcome Measure Data

Analysis Population Description
Safety Analysis Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.	First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
Measure Participants	68	197
Baseline (n=68, 188)	10.3 5%	11.2 5.5%
Post-Baseline (n=66, 197)	7.6 3.7%	13.2 6.4%

25. Secondary Outcome

Title	Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20
Description	All investigator physicians and nurses involved in this study were asked to provide the staff time that could be saved with each administration of rituximab SC as compared with rituximab IV to participants in routine practice afetr Cy 8, 15, 20 and categorized as less than (<) 1 hr, at least 1 hr but <2 hrs, at least 2 hrs but <3 hrs, at least 3 hrs but <4 hrs, >/=4 hrs. Staff were asked not to consider the time needed for the first IV administration. Analysis was done in all participants to show a comparison on the time saved by staffs when administered via SC and IV.
Time Frame	After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	All Participants
Arm/Group Description	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP): First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP): Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
Measure Participants	166
After Cy8: <1 hour (n=166)	11
After Cy8: ≥1 to <2 hours (n=166)	20
After Cy8: ≥2 to <3 hours (n=166)	35
After Cy8: ≥3 to <4 hours (n=166)	18
After Cy8: ≥4 hours (n=166)	16
After Cy15: <1 hour (n=130)	13
After Cy15: ≥1 to <2 hours (n=130)	17
After Cy15: ≥2 to <3 hours (n=126)	34
After Cy15: ≥3 to <4 hours (n=130)	14
After Cy15: ≥4 hours (n=130)	22
After Cy20: <1 hour (n=126)	14
After Cy20: ≥1 to <2 hours (n=126)	32
After Cy20: ≥2 to <3 hours (n=126)	21
After Cy20: ≥3 to <4 hours (n=126)	13
After Cy20: ≥4 hours (n=126)	19

26. Secondary Outcome

Title	Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion
Description	All investigator physicians and nurses involved in this study were asked to complete question i.e. "Which formulation of rituximab (SC or IV) do you think is more convenient?" based on their experience with the rituximab SC and IV formulations across all participants and presented as rituximab SC is much more convenient; rituximab SC is a little more convenient; both formulations are equally convenient; rituximab IV is a little more convenient; and rituximab IV is much more convenient.
Time Frame	After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)

Outcome Measure Data

Analysis Population Description
ITT Population. Here, number of participants analyzed = participants evaluable for the outcome measure. Here "n" = number of participants evaluable for this outcome measure at specified timepoint.

Arm/Group Title	All Participants
Arm/Group Description	Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP): First cycle rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC 1400 mg in combination with up to 8 cycles of CHOP or CVP chemotherapy administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months. Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP): Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
Measure Participants	166
Cy8: Rituximab SC much more convenient (n=166)	81
Cy8: Rituximab SC little more convenient (n=166)	13
Cy8: Both formulations equally convenient (n=166)	2
Cy8: Rituximab IV little more convenient (n=166)	4
Cy8: Rituximab IV much more convenient (n=166)	0
Cy15: Rituximab SC much more convenient (n=130)	88
Cy15: Rituximab SC little more convenient (n=130)	7
Cy15: Both formulations equally convenient (n=130)	5
Cy15: Rituximab IV little more convenient (n=130)	0
Cy15: Rituximab IV much more convenient (n=130)	0
Cy20: Rituximab SC much more convenient (n=126)	88
Cy20: Rituximab SC little more convenient (n=126)	9
Cy20: Both formulations equally convenient (n=126)	2
Cy20: Rituximab IV little more convenient (n=126)	1
Cy20: Rituximab IV much more convenient (n=126)	0

Adverse Events

	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)		Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Time Frame	Baseline up to data cutoff date of 31 Oct 2017 (up to 6 years)
Adverse Event Reporting Description	Safety Analysis Population included all participants who received at least one dose of rituximab, either IV or SC. Safety Analysis Population included 6 participants who were randomized under Rituximab SC arm but withdrew after Cy1 and then analyzed under Rituximab IV arm.

Arm/Group Title	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)		Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
Arm/Group Description	Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.		First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)		Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/210 (36.2%)		74/197 (37.6%)
Blood and lymphatic system disorders
Febrile neutropenia	10/210 (4.8%)		12/197 (6.1%)
Neutropenia	4/210 (1.9%)		6/197 (3%)
Anaemia	1/210 (0.5%)		2/197 (1%)
Thrombocytopenia	1/210 (0.5%)		0/197 (0%)
Cardiac disorders
Acute coronary syndrome	1/210 (0.5%)		0/197 (0%)
Atrial fibrillation	0/210 (0%)		2/197 (1%)
Myocardial infarction	1/210 (0.5%)		1/197 (0.5%)
Acute myocardial infarction	0/210 (0%)		1/197 (0.5%)
Cardiac arrest	1/210 (0.5%)		0/197 (0%)
Cardiac failure congestive	1/210 (0.5%)		1/197 (0.5%)
Myocardial ischaemia	1/210 (0.5%)		0/197 (0%)
Bradycardia	1/210 (0.5%)		0/197 (0%)
Ear and labyrinth disorders
Vertigo	1/210 (0.5%)		2/197 (1%)
Gastrointestinal disorders
Abdominal pain	2/210 (1%)		2/197 (1%)
Constipation	3/210 (1.4%)		0/197 (0%)
Ascites	1/210 (0.5%)		0/197 (0%)
Oral lichen planus	1/210 (0.5%)		0/197 (0%)
Pancreatitis	1/210 (0.5%)		0/197 (0%)
Colitis ulcerative	0/210 (0%)		1/197 (0.5%)
Diarrhoea	0/210 (0%)		1/197 (0.5%)
Duodenal ulcer	1/210 (0.5%)		0/197 (0%)
Enteritis	1/210 (0.5%)		0/197 (0%)
Ileus paralytic	0/210 (0%)		1/197 (0.5%)
Mouth ulceration	0/210 (0%)		1/197 (0.5%)
Proctalgia	1/210 (0.5%)		0/197 (0%)
Vomiting	0/210 (0%)		1/197 (0.5%)
Mesenteric vein thrombosis	1/210 (0.5%)		0/197 (0%)
Abdominal wall haematoma	1/210 (0.5%)		0/197 (0%)
Colitis	0/210 (0%)		1/197 (0.5%)
Large intestine polyp	1/210 (0.5%)		0/197 (0%)
General disorders
Pyrexia	5/210 (2.4%)		6/197 (3%)
Malaise	1/210 (0.5%)		0/197 (0%)
Multi-organ failure	1/210 (0.5%)		0/197 (0%)
Death	2/210 (1%)		0/197 (0%)
Hepatobiliary disorders
Cholangitis	0/210 (0%)		1/197 (0.5%)
Cholecystitis acute	1/210 (0.5%)		0/197 (0%)
Jaundice	0/210 (0%)		1/197 (0.5%)
Infections and infestations
Pneumonia	7/210 (3.3%)		11/197 (5.6%)
Neutropenic sepsis	4/210 (1.9%)		1/197 (0.5%)
Cystitis	1/210 (0.5%)		2/197 (1%)
Lower respiratory tract infection	2/210 (1%)		2/197 (1%)
Urinary tract infection	1/210 (0.5%)		2/197 (1%)
Bronchitis	2/210 (1%)		1/197 (0.5%)
Infection	2/210 (1%)		0/197 (0%)
Sepsis	1/210 (0.5%)		3/197 (1.5%)
Bacterial prostatitis	0/210 (0%)		1/197 (0.5%)
Creutzfeldt-Jakob disease	0/210 (0%)		1/197 (0.5%)
Empyema	0/210 (0%)		1/197 (0.5%)
Gastroenteritis norovirus	1/210 (0.5%)		0/197 (0%)
Giardiasis	0/210 (0%)		1/197 (0.5%)
Meningitis	0/210 (0%)		2/197 (1%)
Otitis externa	1/210 (0.5%)		0/197 (0%)
Pneumocystis jirovecii pneumonia	1/210 (0.5%)		0/197 (0%)
Pneumonia mycoplasmal	0/210 (0%)		1/197 (0.5%)
Postoperative wound infection	0/210 (0%)		1/197 (0.5%)
Respiratory tract infection	1/210 (0.5%)		1/197 (0.5%)
Upper respiratory tract infection	0/210 (0%)		1/197 (0.5%)
Urinary tract infection bacterial	0/210 (0%)		1/197 (0.5%)
Appendicitis	1/210 (0.5%)		1/197 (0.5%)
Cellulitis	1/210 (0.5%)		1/197 (0.5%)
Urosepsis	0/210 (0%)		2/197 (1%)
Abscess	1/210 (0.5%)		0/197 (0%)
Bacteraemia	0/210 (0%)		1/197 (0.5%)
Chronic hepatitis B	0/210 (0%)		1/197 (0.5%)
Erysipelas	0/210 (0%)		1/197 (0.5%)
Hepatitis viral	0/210 (0%)		1/197 (0.5%)
Intestinal sepsis	1/210 (0.5%)		0/197 (0%)
Pulmonary tuberculosis	1/210 (0.5%)		0/197 (0%)
Pyelonephritis	1/210 (0.5%)		0/197 (0%)
Respiratory tract infection fungal	1/210 (0.5%)		0/197 (0%)
Cellulitis gangrenous	1/210 (0.5%)		0/197 (0%)
Injury, poisoning and procedural complications
Stress fracture	1/210 (0.5%)		0/197 (0%)
Ankle fracture	1/210 (0.5%)		0/197 (0%)
Femoral neck fracture	1/210 (0.5%)		0/197 (0%)
Foreign body	1/210 (0.5%)		0/197 (0%)
Multiple injuries	1/210 (0.5%)		0/197 (0%)
Skull fracture	0/210 (0%)		1/197 (0.5%)
Fall	0/210 (0%)		1/197 (0.5%)
Lumbar vertebral fracture	0/210 (0%)		1/197 (0.5%)
Procedural pain	0/210 (0%)		1/197 (0.5%)
Traumatic intracranial haemorrhage	1/210 (0.5%)		0/197 (0%)
Wrist fracture	0/210 (0%)		1/197 (0.5%)
Investigations
Eastern Cooperative Oncology Group performance status worsened	1/210 (0.5%)		0/197 (0%)
International normalised ratio increased	0/210 (0%)		1/197 (0.5%)
Metabolism and nutrition disorders
Hyponatraemia	0/210 (0%)		2/197 (1%)
Tumour lysis syndrome	0/210 (0%)		1/197 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/210 (0.5%)		2/197 (1%)
Osteoarthritis	2/210 (1%)		0/197 (0%)
Arthralgia	0/210 (0%)		2/197 (1%)
Flank pain	0/210 (0%)		1/197 (0.5%)
Pain in extremity	1/210 (0.5%)		0/197 (0%)
Pathological fracture	0/210 (0%)		1/197 (0.5%)
Arthritis	0/210 (0%)		1/197 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/210 (0.5%)		0/197 (0%)
Prostate cancer	1/210 (0.5%)		1/197 (0.5%)
Rectal adenocarcinoma	1/210 (0.5%)		0/197 (0%)
Squamous cell carcinoma of lung	1/210 (0.5%)		0/197 (0%)
Squamous cell carcinoma of skin	1/210 (0.5%)		1/197 (0.5%)
Thyroid cancer	1/210 (0.5%)		0/197 (0%)
Adenocarcinoma of colon	0/210 (0%)		1/197 (0.5%)
Cervix Carcinoma Stage 0	0/210 (0%)		1/197 (0.5%)
Colon cancer	1/210 (0.5%)		1/197 (0.5%)
Kaposi's sarcoma	0/210 (0%)		1/197 (0.5%)
Lung neoplasm malignant	1/210 (0.5%)		0/197 (0%)
Myelodysplastic syndrome	1/210 (0.5%)		0/197 (0%)
Renal cell carcinoma	0/210 (0%)		1/197 (0.5%)
Uterine leiomyoma	0/210 (0%)		1/197 (0.5%)
Adenocarcinoma	1/210 (0.5%)		0/197 (0%)
Breast cancer	0/210 (0%)		1/197 (0.5%)
Plasma cell myeloma	0/210 (0%)		1/197 (0.5%)
Squamous cell carcinoma	0/210 (0%)		1/197 (0.5%)
Nervous system disorders
Coma hepatic	1/210 (0.5%)		0/197 (0%)
Hydrocephalus	0/210 (0%)		1/197 (0.5%)
Migraine	1/210 (0.5%)		0/197 (0%)
Paraesthesia	0/210 (0%)		1/197 (0.5%)
Sciatica	1/210 (0.5%)		0/197 (0%)
Cognitive disorder	2/210 (1%)		0/197 (0%)
Hypoglycaemic coma	1/210 (0.5%)		0/197 (0%)
Transient ischaemic attack	1/210 (0.5%)		0/197 (0%)
Psychiatric disorders
Major depression	1/210 (0.5%)		0/197 (0%)
Bipolar disorder	1/210 (0.5%)		0/197 (0%)
Renal and urinary disorders
Hydronephrosis	0/210 (0%)		2/197 (1%)
Urinary retention	1/210 (0.5%)		0/197 (0%)
Calculus bladder	1/210 (0.5%)		0/197 (0%)
Reproductive system and breast disorders
Pelvic cyst	0/210 (0%)		1/197 (0.5%)
Ovarian cyst	0/210 (0%)		1/197 (0.5%)
Uterovaginal prolapse	0/210 (0%)		1/197 (0.5%)
Uterine polyp	0/210 (0%)		1/197 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/210 (1.4%)		2/197 (1%)
Pulmonary embolism	4/210 (1.9%)		1/197 (0.5%)
Pleural effusion	1/210 (0.5%)		1/197 (0.5%)
Acute respiratory failure	1/210 (0.5%)		1/197 (0.5%)
Pneumothorax	1/210 (0.5%)		0/197 (0%)
Bronchitis chronic	1/210 (0.5%)		0/197 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/210 (0.5%)		0/197 (0%)
Lichen planus	1/210 (0.5%)		0/197 (0%)
Rash	1/210 (0.5%)		0/197 (0%)
Skin ulcer	1/210 (0.5%)		0/197 (0%)
Surgical and medical procedures
Bladder calculus removal	1/210 (0.5%)		0/197 (0%)
Hysterectomy	0/210 (0%)		1/197 (0.5%)
Vascular disorders
Arterial occlusive disease	0/210 (0%)		1/197 (0.5%)
Deep vein thrombosis	1/210 (0.5%)		0/197 (0%)
Hypertensive crisis	1/210 (0.5%)		1/197 (0.5%)
Vena cava thrombosis	0/210 (0%)		1/197 (0.5%)
Subclavian artery occlusion	0/210 (0%)		1/197 (0.5%)
Other (Not Including Serious) Adverse Events
	Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)		Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	187/210 (89%)		186/197 (94.4%)
Blood and lymphatic system disorders
Neutropenia	57/210 (27.1%)		65/197 (33%)
Anaemia	26/210 (12.4%)		30/197 (15.2%)
Leukopenia	23/210 (11%)		13/197 (6.6%)
Gastrointestinal disorders
Nausea	47/210 (22.4%)		65/197 (33%)
Constipation	55/210 (26.2%)		50/197 (25.4%)
Diarrhoea	35/210 (16.7%)		34/197 (17.3%)
Vomiting	27/210 (12.9%)		29/197 (14.7%)
Abdominal pain	25/210 (11.9%)		29/197 (14.7%)
Dyspepsia	14/210 (6.7%)		16/197 (8.1%)
Abdominal pain upper	11/210 (5.2%)		11/197 (5.6%)
Stomatitis	11/210 (5.2%)		12/197 (6.1%)
General disorders
Injection site erythema	0/210 (0%)		27/197 (13.7%)
Fatigue	38/210 (18.1%)		42/197 (21.3%)
Asthenia	27/210 (12.9%)		35/197 (17.8%)
Pyrexia	29/210 (13.8%)		29/197 (14.7%)
Chills	18/210 (8.6%)		16/197 (8.1%)
Mucosal inflammation	12/210 (5.7%)		9/197 (4.6%)
Chest pain	7/210 (3.3%)		14/197 (7.1%)
Injection site pain	0/210 (0%)		16/197 (8.1%)
Oedema peripheral	13/210 (6.2%)		10/197 (5.1%)
Influenza like illness	12/210 (5.7%)		5/197 (2.5%)
Infections and infestations
Upper respiratory tract infection	26/210 (12.4%)		30/197 (15.2%)
Urinary tract infection	28/210 (13.3%)		16/197 (8.1%)
Nasopharyngitis	25/210 (11.9%)		22/197 (11.2%)
Bronchitis	15/210 (7.1%)		15/197 (7.6%)
Sinusitis	10/210 (4.8%)		14/197 (7.1%)
Conjunctivitis	12/210 (5.7%)		9/197 (4.6%)
Influenza	14/210 (6.7%)		9/197 (4.6%)
Pneumonia	4/210 (1.9%)		12/197 (6.1%)
Musculoskeletal and connective tissue disorders
Bone pain	16/210 (7.6%)		20/197 (10.2%)
Back pain	25/210 (11.9%)		18/197 (9.1%)
Myalgia	10/210 (4.8%)		16/197 (8.1%)
Arthralgia	22/210 (10.5%)		26/197 (13.2%)
Pain in extremity	11/210 (5.2%)		22/197 (11.2%)
Muscle spasms	7/210 (3.3%)		17/197 (8.6%)
Nervous system disorders
Paraesthesia	27/210 (12.9%)		30/197 (15.2%)
Neuropathy peripheral	30/210 (14.3%)		24/197 (12.2%)
Dizziness	15/210 (7.1%)		16/197 (8.1%)
Headache	20/210 (9.5%)		27/197 (13.7%)
Hypoaesthesia	7/210 (3.3%)		10/197 (5.1%)
Psychiatric disorders
Insomnia	19/210 (9%)		19/197 (9.6%)
Anxiety	7/210 (3.3%)		11/197 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	32/210 (15.2%)		49/197 (24.9%)
Oropharyngeal pain	16/210 (7.6%)		16/197 (8.1%)
Dyspnoea	13/210 (6.2%)		21/197 (10.7%)
Skin and subcutaneous tissue disorders
Alopecia	23/210 (11%)		28/197 (14.2%)
Erythema	11/210 (5.2%)		19/197 (9.6%)
Pruritus	25/210 (11.9%)		20/197 (10.2%)
Rash	14/210 (6.7%)		20/197 (10.2%)
Vascular disorders
Hypertension	13/210 (6.2%)		12/197 (6.1%)

Limitations/Caveats

[Not Specified]

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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.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800-821-8590
Email	global-roche-genentech-trials@gene.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01200758

Other Study ID Numbers:

BO22334
2010-021377-36

First Posted:

Sep 14, 2010

Last Update Posted:

Nov 27, 2018

Last Verified:

Oct 1, 2018

A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma

Study Details

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Adverse Events

All Cause Mortality

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Other (Not Including Serious) Adverse Events

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