Non-Hodgkin Lymphoma
Conditions
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
Rituximab SC 1400 mg
Cyclophosphamide will be administered as per standard local practice.
Doxorubicin will be administered as per standard local practice.
Vincristine will be administered as per standard local practice.
Prednisone will be administered as per standard local practice.
Fludarabine will be administered as per standard local practice.
Sponsors
Study design
Eligibility
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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | 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]) | 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 Criteria | 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]) | 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 Criteria | 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]) | 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 Score | End 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) Score | Up to 53.8 Months | 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. |
| Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria | From 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
| Arm | Count |
|---|---|
| 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 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 22 | 5 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Screen failure | 10 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | FL Arm | Total | DLBCL Arm |
|---|---|---|---|
| Age, Continuous | 52.8 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 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not applicable as per local regulations | 6 Participants | 22 Participants | 16 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 19 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 24 Participants | 98 Participants | 74 Participants |
| Sex: Female, Male Female | 22 Participants | 78 Participants | 56 Participants |
| Sex: Female, Male Male | 12 Participants | 61 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 95 | 5 / 27 |
| other Total, other adverse events | 58 / 95 | 12 / 27 |
| serious Total, serious adverse events | 11 / 95 | 8 / 27 |
Outcome results
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Paraesthesia | 1.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic | 1.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia | 1.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Leukopenia | 1.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Thrombocytopenia | 1.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site Erythema | 4.2 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain | 4.2 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Burning Sensation | 2.1 Percentage of Participants % |
| DLBCL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Erythema | 2.1 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site Erythema | 7.4 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Paraesthesia | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Thrombocytopenia | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Burning Sensation | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia | 3.7 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Erythema | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain | 0 Percentage of Participants % |
| FL Arm | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Leukopenia | 0 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site, Injection Site Pain | 3.3 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Paraesthesia | 0.8 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Thrombocytopenia | 0.8 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Dermatitis Allergic | 0.8 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | General Disorders And Administration Site Conditions, Injection Site Erythema | 4.9 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, Leukopenia | 0.8 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Skin And Subcutaneous Tissue Disorders, Erythema | 1.6 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Blood And Lymphatic System Disorders, And Lymphatic System Disorders, Anaemia | 1.6 Percentage of Participants % |
| Overall Population | Percentage of Participants With Administration-Associated Reactions (AARs) | Nervous System Disorders, Burning Sensation | 1.6 Percentage of Participants % |
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DLBCL Arm | Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response Criteria | NA Months |
| FL Arm | Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response Criteria | NA Months |
| Overall Population | Disease-Free Survival (DFS) as Assessed by Investigator According to IWG Response Criteria | NA Months |
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DLBCL Arm | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab IV | NA Months |
| DLBCL Arm | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab SC | NA Months |
| FL Arm | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab SC | 45.5 Months |
| FL Arm | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab IV | 53.8 Months |
| Overall Population | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab IV | 53.8 Months |
| Overall Population | Event-Free Survival (EFS) as Assessed by Investigator According to International Working Group (IWG) Response Criteria | From first dose of rituximab SC | 45.5 Months |
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)
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DLBCL Arm | Overall Survival (OS) | From first dose of rituximab IV | 51.4 Months |
| DLBCL Arm | Overall Survival (OS) | From first dose of rituximab SC | 51.4 Months |
| FL Arm | Overall Survival (OS) | From first dose of rituximab IV | NA Months |
| FL Arm | Overall Survival (OS) | From first dose of rituximab SC | NA Months |
| Overall Population | Overall Survival (OS) | From first dose of rituximab IV | NA Months |
| Overall Population | Overall Survival (OS) | From first dose of rituximab SC | NA Months |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DLBCL Arm | Patient-Reported Rituximab Administration Questionnaire (RASQ) Score | 70.5 Scores on a Scale | Standard Deviation 20.76 |
| FL Arm | Patient-Reported Rituximab Administration Questionnaire (RASQ) Score | 69.2 Scores on a Scale | Standard Deviation 19.83 |
| Overall Population | Patient-Reported Rituximab Administration Questionnaire (RASQ) Score | 70.2 Scores on a Scale | Standard Deviation 20.48 |
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DLBCL Arm | Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria | 74.2 Percentage |
| FL Arm | Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria | 76.5 Percentage |
| Overall Population | Percentage of Participants With CR/CRu as Assessed by Investigator According to IWG Response Criteria | 74.5 Percentage |
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DLBCL Arm | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab IV | NA Months |
| DLBCL Arm | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab SC | NA Months |
| FL Arm | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab IV | 53.8 Months |
| FL Arm | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab SC | 45.5 Months |
| Overall Population | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab IV | 53.8 Months |
| Overall Population | Progression-Free Survival (PFS) as Assessed by Investigator According to IWG Response Criteria | From first dose of rituximab SC | 44.5 Months |