MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01987505
• Collaborator: (none)
• Enrollment: 140
• Locations: 39
• Arm: 1
• Actual Duration (Months): 41
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This open-label, single-arm, phase IIIb study will evaluate the safety of switching from intravenous (IV) to subcutaneous (SC) administration of rituximab during first-line treatment for participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have already received at least one full dose of rituximab IV. Participants with FL will be given 1400 mg rituximab SC during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). 1400 mg SC of rituximab will be given to participants with DLBCL once monthly for 4-7 cycles. Treatment duration is expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non Hodgkin	Drug: Rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label, Single-arm, Phase IIIb Clinical Trial to Evaluate the Safety of Switching From Intravenous Rituximab to Subcutaneous Rituximab During First Line Treatment for CD20+ Non-Hodgkin's Follicular Lymphoma and Diffuse Large B-cell Lymphoma.
• Actual Study Start Date: Nov 11, 2013
• Actual Primary Completion Date: Apr 11, 2017
• Actual Study Completion Date: Apr 11, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Subcutaneous Rituximab Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab will be treated with subcutaneous (SC) rituximab. Participants with FL will be administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL will be administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration is expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.

Drug: Rituximab; 1400 mg will be injected subcutaneously (SC).; Other Names: MabThera Rituxan

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Administration-Associated Reactions (AARs) [From start of treatment to end of treatment (up to 32 months)]

   AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab SC administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Secondary Outcome Measures

1. Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs) [From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)]

   An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.

2. Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs) [From start of treatment to end of treatment (up to 32 months)]

   Grading of IIRRs was completed according to the CTCAE, version 4.0.

3. Percentage of Participants With At Least One Serious Adverse Event (SAE) [From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)]

   SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

4. Event-Free Survival (EFS) [From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)]

   EFS was defined as the time from first dose of rituximab IV to first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.

5. Progression-Free Survival (PFS) [From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)]

   PFS was defined as the time from first dose of rituximab IV to the first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or death from any cause. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.

6. Overall Survival (OS) [From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)]

   OS was defined as the time from first dose of rituximab IV to death from any cause.

7. Disease-Free Survival (DFS) [From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)]

   DFS was assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow. Reported here is the truncated mean estimate based on Kaplan-Meier analysis.

8. Treatment Response Rate [4-6 weeks after the last dose of Induction (Up to approximately 8 months)]

   Treatment response rate was classified according to the International Working Group (IWG) response criteria: CR/Cru, partial response (PR), stable disease (SD) and PD. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow; PR: >/= 50% decrease lymph nodes and nodal mass size; decrease in liver/spleen size, no new sites; SD: less than a PR, but is not PD; PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 18 and ≤ 80 years at time of enrolment.

• Life expectancy ≥ 6 months.

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.

• Fertile men or women of childbearing potential must use effective contraception until at least 12 months after the last dose; women must not be pregnant.

• Histologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL) or CD20+ follicular Non-Hodgkin Lymphoma (FL) grade 1, 2 or 3a according to the World Health Organisation Classification system.

Induction only:

• Participants with Follicular Lymphoma should meet Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria to initiate treatment.

• At least tumor >/= 1.5 cm as measured by computed tomography (CT) scan.

FL treatment-related criteria

• Currently being treated with rituximab IV during first-line therapy and has received at least one full dose of rituximab IV.

Exclusion Criteria:

• Transformed lymphoma.

• Primary central nervous system lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, primary cutaneous DLBCL or histologic evidence of transformation to a Burkitt lymphoma.

• History of other cancer, including one that has been treated but not with curative intent, unless the cancer has been in remission without treatment for >/= 5 years prior to dosing. Note: Participants with a history of cured skin cancer or in situ carcinoma of the cervix are eligible for the study.

• Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Note: Participants receiving corticosteroid treatment with </= 30 mg/day of prednisone or equivalent must be on a stable regimen for at least 4 weeks prior to start of dosing.

• Inadequate renal, hematologic, or hepatic function.

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.

• For participants with DLBCL: Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone), including prior anthracycline treatment.

• For participants with FL: contraindication to standard chemotherapy.

• Other serious underlying medical conditions.

• Recent major surgery (within 4 weeks prior to dosing), other than for diagnosis.

• Active and/or severe infections (excluding nail fungal infections) or any infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to dosing.

• Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Note: Participants testing positive for Hepatitis B or C virus antibodies but with an undetectable viral load may be included.

• History of Human Immunodeficiency Virus (HIV) positive status.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital De Txagorritxu; Servicio de Hematologia	Vitoria	Alava	Spain	01009
2	Hospital General de Elda; Servicio de Hematologia	Elda	Alicante	Spain	03600
3	Hospital de Granollers, Servicio de Hematología	Granollers	Barcelona	Spain	08400
4	Hospital Mutua de Terrassa; Servicio de Hematologia	Terrassa	Barcelona	Spain	08221
5	Hospital Son Llatzer; Servicio de Hematologia	Palma de Mallorca	Islas Baleares	Spain	07198
6	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia	La Coruna	LA Coruña	Spain	15006
7	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Hematologia	Santiago de Compostela	LA Coruña	Spain	15706
8	Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia	Logroño	LA Rioja	Spain	26006
9	Complejo Asistencial de León, Servicio de Hematología	León	Leon	Spain	24008
10	Hospital Universitario de Fuenlabrada; Servicio de Hematologia	Fuenlabrada	Madrid	Spain	28943
11	Hospital Severo Ochoa; Servicio de Hematologia	Leganes	Madrid	Spain	28911
12	Hosital Universitario de Mostoles;Servicio de Hematologia	Mostoles	Madrid	Spain	28935
13	Clinica Universitaria de Navarra; Servicio de Hematologia	Pamplona	Navarra	Spain	31008
14	Hospital de Navarra, Servicio de Hematología	Pamplona	Navarra	Spain	31008
15	Complejo Hospitalario Universitario de Vigo; Servicio de Hematologia	Vigo	Pontevedra	Spain	36204
16	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia	Santa Cruz de Tenerife	Tenerife	Spain	38010
17	Hospital de Basurto; Servicio de Hematologia	Bilbao	Vizcaya	Spain	48013
18	Hospital de Galdakano; Servicio de Hematologia	Galdakao	Vizcaya	Spain	48960
19	Complejo Hospitalario Torrecardenas; Servicio de Hematologia	Almeria		Spain	04009
20	Hospital Universitario de Burgos, Servicio de Hematología	Burgos		Spain	09006
21	Hospital General de Castellon; Servicio de Hematologia	Castellon		Spain	12004
22	Hospital Universitario Reina Sofia; Servicio de Hematologia	Cordoba		Spain	14004
23	Hospital Universitario Virgen de las Nieves; Servicio de Hematologia	Granada		Spain	18014
24	Hospital Universitario de Gaudalajara; Hematología	Guadalajara		Spain	19002
25	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Hematologia	Lerida		Spain	25198
26	Hospital Infanta Leonor; Servicio de Hematologia	Madrid		Spain	28031
27	Fundacion Jimenez Diaz; Servicio de Hematologia	Madrid		Spain	28040
28	Hospital Universitario Clínico San Carlos; Servicio de Hematología	Madrid		Spain	28040
29	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia	Madrid		Spain	28050
30	Hospital Universitario Puerta de Hierro; Servicio de Hematologia	Madrid		Spain	28222
31	Hospital Universitario Principe de Asturias; Servicio de Hematología	Madrid		Spain	28805
32	Hospital Univ. Virgen de la Victoria	Malaga		Spain	29010
33	Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología	Murcia		Spain	30008
34	Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia	Murcia		Spain	30120
35	Complejo Hospitalario de Pontevedra; Servicio de Hematologia	Pontevedra		Spain	36071
36	Complejo Asistencial de Segovia	Segovia		Spain	40002
37	Hospital Universitario Virgen Macarena; Servicio de Hematologia	Sevilla		Spain	41009
38	Hospital Univ. Nuestra Señora de Valme; Servicio de Hematologia	Sevilla		Spain	41014
39	Hospital de Rio Hortega; Servicio de Hematologia	Valladolid		Spain	47010

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - May 30, 2013
• Statistical Analysis Plan - Sep 11, 2017

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01987505
• Other Study ID Numbers: ML28943; 2013-001118-14
• First Posted: Nov 19, 2013
• Last Update Posted: Dec 26, 2018
• Last Verified: Dec 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab

Study Results

Participant Flow

Arm/Group Title	Subcutaneous Rituximab
Arm/Group Description	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Period Title: Overall Study
STARTED	140
COMPLETED	106
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	Diffuse Large B-Cell Lymphoma	Follicular Lymphoma	Total
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Total of all reporting groups
Overall Participants	29	111	140
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (12.0)	59.6 (12.5)	60.2 (12.4)
Sex: Female, Male (Count of Participants)
Female	17 58.6%	58 52.3%	75 53.6%
Male	12 41.4%	53 47.7%	65 46.4%
Race/Ethnicity, Customized (Count of Participants)
Black	0 0%	1 0.9%	1 0.7%
Caucasian	29 100%	110 99.1%	139 99.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Administration-Associated Reactions (AARs)
Description	AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab SC administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
Time Frame	From start of treatment to end of treatment (up to 32 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
At Least One AAR	34.5 119%	52.3 47.1%	48.6 34.7%
At Least One AAR Grade ≥ 3	0 0%	2.7 2.4%	2.1 1.5%
At Least One Serious AARs	0 0%	1.8 1.6%	1.4 1%
Generalised or Remote from the Injection Site AARs	57.9 199.7%	11.1 10%	15.1 10.8%
Localised at the injection site AARs	42.1 145.2%	88.9 80.1%	84.9 60.6%

2. Secondary Outcome

Title	Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs)
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.
Time Frame	From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Number [percentage of participants]	48.3 166.6%	36.0 32.4%	38.6 27.6%

3. Secondary Outcome

Title	Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs)
Description	Grading of IIRRs was completed according to the CTCAE, version 4.0.
Time Frame	From start of treatment to end of treatment (up to 32 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Number [percentage of participants]	0.0 0%	2.7 2.4%	2.1 1.5%

4. Secondary Outcome

Title	Percentage of Participants With At Least One Serious Adverse Event (SAE)
Description	SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Time Frame	From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)

Outcome Measure Data

Analysis Population Description

Safety Population included all enrolled participants who received at least one dose of study medication.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Number [percentage of participants]	37.9 130.7%	27.9 25.1%	30.0 21.4%

5. Secondary Outcome

Title	Event-Free Survival (EFS)
Description	EFS was defined as the time from first dose of rituximab IV to first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.
Time Frame	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all enrolled participants.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Mean (95% Confidence Interval) [months]	25.79	54.39	52.314

6. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from first dose of rituximab IV to the first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or death from any cause. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.
Time Frame	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Mean (95% Confidence Interval) [months]	27.952	54.389	53.118

7. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from first dose of rituximab IV to death from any cause.
Time Frame	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Mean (95% Confidence Interval) [months]	37.42	60.61	59.516

8. Secondary Outcome

Title	Disease-Free Survival (DFS)
Description	DFS was assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow. Reported here is the truncated mean estimate based on Kaplan-Meier analysis.
Time Frame	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Mean (95% Confidence Interval) [months]	26.062	NA	33.044

9. Secondary Outcome

Title	Treatment Response Rate
Description	Treatment response rate was classified according to the International Working Group (IWG) response criteria: CR/Cru, partial response (PR), stable disease (SD) and PD. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow; PR: >/= 50% decrease lymph nodes and nodal mass size; decrease in liver/spleen size, no new sites; SD: less than a PR, but is not PD; PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.
Time Frame	4-6 weeks after the last dose of Induction (Up to approximately 8 months)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants.

Arm/Group Title	Diffuse Large B-Cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Subcutaneous Rituximab
Arm/Group Description	Participants with diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Treatment duration was expected to last to 32 months for participants with FL.	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
Measure Participants	29	111	140
Complete Response (CR)	62.1 214.1%	66.7 60.1%	64.3 45.9%
Complete Response Unconfirmed (CRU)	3.4 11.7%	7.4 6.7%	5.4 3.9%
Partial Response (PR)	3.4 11.7%	11.1 10%	7.1 5.1%
Stable Disease (SD)	0.0 0%	3.7 3.3%	1.8 1.3%
Progressive disease (PD)	17.2 59.3%	7.4 6.7%	12.5 8.9%
Unable to Assess (UA)	6.9 23.8%	0.0 0%	3.6 2.6%
Not Evaluable	6.9 23.8%	3.7 3.3%	5.4 3.9%

Adverse Events

Time Frame	From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
Adverse Event Reporting Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Safety Population included all enrolled participants who received at least one dose of study medication.
Arm/Group Title	Subcutaneous Rituximab
Arm/Group Description	Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab were treated with subcutaneous (SC) rituximab during first-line treatment. Participants with FL were administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL were administered 1400 mg SC of rituximab once monthly for 4-7 cycles. Treatment duration was expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.
All Cause Mortality
	Subcutaneous Rituximab
	Affected / at Risk (%)	# Events
Total	4/140 (2.9%)
Serious Adverse Events
	Subcutaneous Rituximab
	Affected / at Risk (%)	# Events
Total	42/140 (30%)
Blood and lymphatic system disorders
Agranulocytosis	1/140 (0.7%)
Febrile neutropenia	12/140 (8.6%)
Neutropenia	10/140 (7.1%)
Cardiac disorders
Atrial fibrillation	1/140 (0.7%)
Ear and labyrinth disorders
Vertigo	1/140 (0.7%)
Gastrointestinal disorders
Abdominal pain	2/140 (1.4%)
Abdominal pain upper	1/140 (0.7%)
Enteritis	1/140 (0.7%)
Gastrointestinal disorder	1/140 (0.7%)
Gastrointestinal haemorrhage	1/140 (0.7%)
Intestinal obstruction	1/140 (0.7%)
Paraesthesia oral	1/140 (0.7%)
Umbilical hernia	1/140 (0.7%)
General disorders
Pyrexia	1/140 (0.7%)
Infections and infestations
Enterobacter bacteraemia	1/140 (0.7%)
Cellulitis	1/140 (0.7%)
Escherichia bacteraemia	1/140 (0.7%)
Gastroenteritis	3/140 (2.1%)
Influenza	1/140 (0.7%)
Lung infection	1/140 (0.7%)
Pneumonia	4/140 (2.9%)
Pneumonia pneumococcal	2/140 (1.4%)
Respiratory tract infection	4/140 (2.9%)
Sepsis	1/140 (0.7%)
Urinary tract infection	1/140 (0.7%)
Urosepsis	2/140 (1.4%)
Injury, poisoning and procedural complications
Toxicity to various agents	1/140 (0.7%)
Metabolism and nutrition disorders
Hypomagnesaemia	1/140 (0.7%)
Malnutrition	1/140 (0.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/140 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	1/140 (0.7%)
Gastric neoplasm	1/140 (0.7%)
Malignant melanoma	1/140 (0.7%)
Prostate cancer	1/140 (0.7%)
Nervous system disorders
Presyncope	1/140 (0.7%)
Syncope	1/140 (0.7%)
Reproductive system and breast disorders
Prostatitis	1/140 (0.7%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/140 (0.7%)
Pulmonary mass	1/140 (0.7%)
Vascular disorders
Venous thrombosis	1/140 (0.7%)
Other (Not Including Serious) Adverse Events
	Subcutaneous Rituximab
	Affected / at Risk (%)	# Events
Total	117/140 (83.6%)
Blood and lymphatic system disorders
Anaemia	13/140 (9.3%)
Neutropenia	24/140 (17.1%)
Gastrointestinal disorders
Abdominal pain	13/140 (9.3%)
Diarrhoea	22/140 (15.7%)
Dyspepsia	8/140 (5.7%)
Nausea	12/140 (8.6%)
General disorders
Asthenia	31/140 (22.1%)
Injection site erythema	12/140 (8.6%)
Pain	9/140 (6.4%)
Pyrexia	14/140 (10%)
Infections and infestations
Respiratory tract infection	23/140 (16.4%)
Upper respiratory tract infection	12/140 (8.6%)
Urinary tract infection	11/140 (7.9%)
Viral upper respiratory tract infection	21/140 (15%)
Musculoskeletal and connective tissue disorders
Arthralgia	13/140 (9.3%)
Back pain	15/140 (10.7%)
Nervous system disorders
Dizziness	7/140 (5%)
Headache	11/140 (7.9%)
Paraesthesia	14/140 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	14/140 (10%)
Productive cough	9/140 (6.4%)
Skin and subcutaneous tissue disorders
Erythema	36/140 (25.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.