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Safety Study of Rituximab (SC) Administered in Participants With CD20+ DLBCL or CD20+ Follicular NHL Grade 1 to 3A

An Open-Label, Multinational, Multicenter, Phase IIIB Study to Assess Safety of Rituximab Following Subcutaneous Administration in Patients With CD20+ DLBCL or CD20+ Follicular NHL Grade 1 to 3A

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02406092
Enrollment
139
Registered
2015-04-02
Start date
2015-10-13
Completion date
2021-06-30
Last updated
2024-11-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-Hodgkin Lymphoma

Brief summary

This open-label, single-arm study will evaluate the safety of rituximab subcutaneously (SC) administered during first line treatment for follicular non-Hodgkin's lymphoma (NHL) (Induction and/or Maintenance treatment plus 24 months of follow up), or diffuse large B-cell lymphoma (DLBCL) (treatment plus 24 months of follow-up).

Interventions

DRUGRituximab

Rituximab SC 1400 mg

DRUGCyclophosphamide

Cyclophosphamide will be administered as per standard local practice.

DRUGDoxorubicin

Doxorubicin will be administered as per standard local practice.

DRUGVincristine

Vincristine will be administered as per standard local practice.

DRUGPrednisone

Prednisone will be administered as per standard local practice.

DRUGFludarabine

Fludarabine will be administered as per standard local practice.

Sponsors

Hoffmann-La Roche
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No

Inclusion criteria

* Histologically confirmed, cluster of differentiation (CD)20+ DLBCL or CD20+ follicular NHL grade 1 to 3a, according to the world health organization (WHO) classification system * Currently being treated with rituximab IV in the Induction or Maintenance setting, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 milligrams per square meter (mg/m\^2) administered without interruption or early discontinuation because of tolerability issues * Expectation and current ability for the participants to receive at least four additional cycles of treatment during the Induction phase or six additional cycles of treatment during the Maintenance phase (participants with follicular NHL)

Exclusion criteria

* Transformed lymphoma or FL IIIB * History of other malignancy that could affect compliance with the protocol or interpretation of results. This includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for greater than or equal to (\>/=) 5 years prior to dosing

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants With Administration-Associated Reactions (AARs)Within 24 hours of each rituximab SC administration (maximum treatment duration up to 32 months for FL participants and up to 8 months for DLBCL participants)AARs defined as all related adverse events (AEs) occurring within 24 hours of rituximab SC administration, including infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof.

Secondary

MeasureTime frameDescription
Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab IV and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])PFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to the first occurrence of progression or relapse, according to the IWG response criteria (Cheson et al. 1999) or other country standards, or death from any cause.
Overall Survival (OS)From first dose of rituximab IV and SC until death from any cause (up to end of induction treatment [Up to 51.1 Months])OS is defined as the time from first dose of rirtuximab (analysed using both first dose of IV and first dose of SC) until death from any cause.
Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response CriteriaFrom the date of the initial complete response (CR)/complete response unconfirmed (CRu) until date of relapse or death from any cause (up to end of induction treatment [Up to 32.7 Months])DFS will be assessed at the end of induction treatment in patients achieving CR/CRu and is defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause.
Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab intravenous (IV) and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])EFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to first occurrence of progression or relapse, according to the IWG response criteria or other country standards, or initiation of a non-protocolspecified anti-lymphoma therapy or death, whichever occurs first.
Healthcare Professional Questionnaire ScoreEnd of treatment (Month 24 for FL participants and Month 8 for DLBCL participants)Planned Healthcare Professional Questionnaiere was not collected during the study therefore no data to report
Patient-Reported Rituximab Administration Questionnaire (RASQ) ScoreUp to 53.8 MonthsThe RASQ measures the overall participant satisfaction and is a 20-item questionnaire measuring the impact of the treatment administration on 5 domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. Each question's answer is chosen from 1 (minimum)-5(maximum score indicating less severity) score range. For each domain was scored using the following formula: Domain score = \[(Sum of completed item (question) responses / Number of completed items) - 1\] x 100 / (Maximum possible item response value - Minimum possible item response value) The final RASQ domains is calculated using the formula: RASQ domain score = (Mean of completed item responses - 1) x 25, scores ranging from 1-100 with higher scores indicative of more positive feelings toward therapy. Lower number representing lower satisfaction and higher is the higher satisfaction by the participants.
Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab until first occurrence of progression or relapse (up to end of induction treatment [Up to 32 Months])CR/CRu: Response assessments 4 - 6 weeks after the last dose of induction treatment will be based on the Investigator's assessment, completed according to the original International Working Group (IWG) response criteria for response assessment of lymphoma (Cheson et al. 1999).

Countries

Algeria, Morocco, Tunisia

Participant flow

Recruitment details

Total of 139 participants mentioned below in the table were recruited and enrolled.

Pre-assignment details

139 participants (105 with DLBCL and 34 with FL) in the intent-to-treat (ITT) population; 122 participants (95 with DLBCL and 27 with FL) in the safety population. From 139 participants, 122 were dosed at least 1 dose were included in Safety Analysis Set.

Participants by arm

ArmCount
DLBCL Arm
Participants with DLBCL received rituximab SC 1400 milligrams (mg) once a month for a minimum of 4 cycles as induction therapy. Participants with FL will continue to receive rituximab once in 2 months for a minimum of 6 cycles as maintenance therapy according to local standards of care. Participants will also receive standard chemotherapy regimen (CHOP \[cyclophosphamide+doxorubicin+vincristine+prednisone\], CVP \[cyclophosphamide+vincristine+prednisone\] or FC \[fludarabine+cyclophosphamide\]) during induction.
105
FL Arm
Participants with FL received rituximab SC 1400 milligrams (mg) once a month for a minimum of 4 cycles as induction therapy. Participants with FL will continue to receive rituximab once in 2 months for a minimum of 6 cycles as maintenance therapy according to local standards of care. Participants will also receive standard chemotherapy regimen (CHOP \[cyclophosphamide+doxorubicin+vincristine+prednisone\], CVP \[cyclophosphamide+vincristine+prednisone\] or FC \[fludarabine+cyclophosphamide\]) during induction.
34
Total139

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event10
Overall StudyDeath225
Overall StudyLost to Follow-up41
Overall StudyScreen failure107
Overall StudyWithdrawal by Subject10

Baseline characteristics

CharacteristicFL ArmTotalDLBCL Arm
Age, Continuous52.8 Years
STANDARD_DEVIATION 12.65
51.7 Years
STANDARD_DEVIATION 13.48
51.3 Years
STANDARD_DEVIATION 13.78
Race/Ethnicity, Customized
Hispanic or Latino
0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
Not applicable as per local regulations
6 Participants22 Participants16 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
4 Participants19 Participants15 Participants
Race/Ethnicity, Customized
Other
24 Participants98 Participants74 Participants
Sex: Female, Male
Female
22 Participants78 Participants56 Participants
Sex: Female, Male
Male
12 Participants61 Participants49 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
22 / 955 / 27
other
Total, other adverse events
58 / 9512 / 27
serious
Total, serious adverse events
11 / 958 / 27

Outcome results

Primary

Percentage of Participants With Administration-Associated Reactions (AARs)

AARs defined as all related adverse events (AEs) occurring within 24 hours of rituximab SC administration, including infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof.

Time frame: Within 24 hours of each rituximab SC administration (maximum treatment duration up to 32 months for FL participants and up to 8 months for DLBCL participants)

Population: Safety Population

ArmMeasureGroupValue (NUMBER)
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Paraesthesia1.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic1.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia1.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Leukopenia1.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Thrombocytopenia1.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site Erythema4.2 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain4.2 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Burning Sensation2.1 Percentage of Participants %
DLBCL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Erythema2.1 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site Erythema7.4 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Paraesthesia0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Thrombocytopenia0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Burning Sensation0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia3.7 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Erythema0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain0 Percentage of Participants %
FL ArmPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Leukopenia0 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain3.3 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Paraesthesia0.8 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Thrombocytopenia0.8 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic0.8 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)General Disorders And Administration Site Conditions, Injection Site Erythema4.9 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, Leukopenia0.8 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Skin And Subcutaneous Tissue Disorders, Erythema1.6 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia1.6 Percentage of Participants %
Overall PopulationPercentage of Participants With Administration-Associated Reactions (AARs)Nervous System Disorders, Burning Sensation1.6 Percentage of Participants %
Secondary

Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response Criteria

DFS will be assessed at the end of induction treatment in patients achieving CR/CRu and is defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause.

Time frame: From the date of the initial complete response (CR)/complete response unconfirmed (CRu) until date of relapse or death from any cause (up to end of induction treatment [Up to 32.7 Months])

Population: ITT

ArmMeasureValue (MEDIAN)
DLBCL ArmDisease-Free Survival (DFS) as Assessed by Investigator According to IWG Response CriteriaNA Months
FL ArmDisease-Free Survival (DFS) as Assessed by Investigator According to IWG Response CriteriaNA Months
Overall PopulationDisease-Free Survival (DFS) as Assessed by Investigator According to IWG Response CriteriaNA Months
Secondary

Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria

EFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to first occurrence of progression or relapse, according to the IWG response criteria or other country standards, or initiation of a non-protocolspecified anti-lymphoma therapy or death, whichever occurs first.

Time frame: From first dose of rituximab intravenous (IV) and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])

Population: ITT

ArmMeasureGroupValue (MEDIAN)
DLBCL ArmEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab IVNA Months
DLBCL ArmEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab SCNA Months
FL ArmEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab SC45.5 Months
FL ArmEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab IV53.8 Months
Overall PopulationEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab IV53.8 Months
Overall PopulationEvent-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response CriteriaFrom first dose of rituximab SC45.5 Months
Secondary

Healthcare Professional Questionnaire Score

Planned Healthcare Professional Questionnaiere was not collected during the study therefore no data to report

Time frame: End of treatment (Month 24 for FL participants and Month 8 for DLBCL participants)

Secondary

Overall Survival (OS)

OS is defined as the time from first dose of rirtuximab (analysed using both first dose of IV and first dose of SC) until death from any cause.

Time frame: From first dose of rituximab IV and SC until death from any cause (up to end of induction treatment [Up to 51.1 Months])

Population: ITT

ArmMeasureGroupValue (MEDIAN)
DLBCL ArmOverall Survival (OS)From first dose of rituximab IV51.4 Months
DLBCL ArmOverall Survival (OS)From first dose of rituximab SC51.4 Months
FL ArmOverall Survival (OS)From first dose of rituximab IVNA Months
FL ArmOverall Survival (OS)From first dose of rituximab SCNA Months
Overall PopulationOverall Survival (OS)From first dose of rituximab IVNA Months
Overall PopulationOverall Survival (OS)From first dose of rituximab SCNA Months
Secondary

Patient-Reported Rituximab Administration Questionnaire (RASQ) Score

The RASQ measures the overall participant satisfaction and is a 20-item questionnaire measuring the impact of the treatment administration on 5 domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. Each question's answer is chosen from 1 (minimum)-5(maximum score indicating less severity) score range. For each domain was scored using the following formula: Domain score = \[(Sum of completed item (question) responses / Number of completed items) - 1\] x 100 / (Maximum possible item response value - Minimum possible item response value) The final RASQ domains is calculated using the formula: RASQ domain score = (Mean of completed item responses - 1) x 25, scores ranging from 1-100 with higher scores indicative of more positive feelings toward therapy. Lower number representing lower satisfaction and higher is the higher satisfaction by the participants.

Time frame: Up to 53.8 Months

Population: Safety Population

ArmMeasureValue (MEAN)Dispersion
DLBCL ArmPatient-Reported Rituximab Administration Questionnaire (RASQ) Score70.5 Scores on a ScaleStandard Deviation 20.76
FL ArmPatient-Reported Rituximab Administration Questionnaire (RASQ) Score69.2 Scores on a ScaleStandard Deviation 19.83
Overall PopulationPatient-Reported Rituximab Administration Questionnaire (RASQ) Score70.2 Scores on a ScaleStandard Deviation 20.48
Secondary

Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria

CR/CRu: Response assessments 4 - 6 weeks after the last dose of induction treatment will be based on the Investigator's assessment, completed according to the original International Working Group (IWG) response criteria for response assessment of lymphoma (Cheson et al. 1999).

Time frame: From first dose of rituximab until first occurrence of progression or relapse (up to end of induction treatment [Up to 32 Months])

Population: ITT

ArmMeasureValue (NUMBER)
DLBCL ArmPercentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria74.2 Percentage
FL ArmPercentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria76.5 Percentage
Overall PopulationPercentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria74.5 Percentage
Secondary

Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria

PFS is defined as the time from first dose of rituximab (analysed using both first dose of IV and first dose of SC) to the first occurrence of progression or relapse, according to the IWG response criteria (Cheson et al. 1999) or other country standards, or death from any cause.

Time frame: From first dose of rituximab IV and SC until first occurrence of progression or relapse (up to end of induction treatment [Up to 53.8 Months])

Population: ITT

ArmMeasureGroupValue (MEDIAN)
DLBCL ArmProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab IVNA Months
DLBCL ArmProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab SCNA Months
FL ArmProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab IV53.8 Months
FL ArmProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab SC45.5 Months
Overall PopulationProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab IV53.8 Months
Overall PopulationProgression-Free Survival (PFS) as Assessed by Investigator According to IWG Response CriteriaFrom first dose of rituximab SC44.5 Months

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026