Diffuse Large B-Cell Lymphoma, Non-Hodgkin's Lymphoma
Conditions
Brief summary
This multi-center, open-label, randomized study will evaluate the participant preference with subcutaneous versus intravenous administration of MabThera/Rituxan (rituximab) in participants with CD20+ diffuse large B-cell lymphoma or CD20+ follicular non-Hodgkin's lymphoma. In Arm A, participants will receive MabThera/Rituxan 375 mg/m2 intravenously (IV) on Day 1 of Cycle 1 and MabThera/Rituxan 1400 mg subcutaneously (SC) on Day 1 of Cycles 2-4, followed by MabThera/Rituxan IV in Cycles 5-8. Participants in Arm B will receive MabThera/Rituxan IV in Cycles 1-4 and SC in Cycles 5-8. All participants will receive 6-8 cycles of standard chemotherapy (according to local country practice) with 8 cycles of MabThera/Rituxan. Anticipated time on study treatment is up to 24 weeks.
Interventions
DRUGCyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone/Prednisolone (CHOP)
Standard chemotherapy
DRUGCyclophosphamide, Vincristine, Prednisone/Prednisolone (CVP)
Standard chemotherapy
DRUGBendamustine
Standard chemotherapy
DRUGRituximab
1400 mg subcutaneously (SC), Day 1 Cycles 2-4
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult participants , \>/= 18 and \</= 80 years of age * Histologically confirmed, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2, or 3a, according to World Health Organization (WHO) classification * An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion \>/= 7.5 cm, or Follicular Lymphoma International Prognostic Index (FLIPI; low, intermediate or high risk) * At least one bi-dimensionally measurable lesion defined as \>/=1.5 cm in its largest dimension on CT scan * Eastern Cooperative Oncology Group (ECOG) performance status \</= 3
Exclusion criteria
* Transformed lymphoma or follicular lymphoma IIIB * Primary central nervous system (CNS) lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis * History of other malignancy that could affect compliance with the protocol or interpretation of the results; this includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission for \>/= 5 years prior to enrolment; participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible * Prior therapy for DLBCL or NHL, with the exception of nodal biopsy or local irradiation * Prior treatment with cytotoxic drugs (with the exclusion of intrathecal methotrexate for CNS prophylaxis in DLBCL) or rituximab for another condition, or prior use of an anti-CD20 drug * Prior use of monoclonal antibody within 3 months prior to randomization * Chemotherapy or other investigational therapy within 28 days prior to randomization * Ongoing corticosteroid use \> 30 mg/day prednisolone or equivalent * Inadequate renal. hematologic or hepatic function * Active and/or severe infection or any major episode of infection within 4 weeks prior to randomization * Active hepatitis B virus or active hepatitis C virus infection * History of human immunodeficiency (HIV) seropositive status * A positive pregnancy test in women of childbearing potential * Life expectancy of less than 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6 | Cycle 6 (Up to 24 weeks) | Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing cycle 6. |
| Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8 | Cycle 8 (Up to 32 weeks) | Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing Cycle 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | During Cycle 4, 8 of treatment (Up to 32 weeks) | CTSQ is a validated 16-item questionnaire that measures three domains related to participants' satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants. |
| Rituximab Administration Satisfaction Questionnaire (RASQ) Score | During Cycle 4, 8 of treatment (Up to 32 weeks) | The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants. |
| Complete Response (CR) Rate | 28 days (± 3 days) after Day 1 of the last dose of induction treatment | CR rate was assessed according to the International Working Group (IWG) Response Criteria (CHESON ET AL. 1999) and included CR and CR unconfirmed (CRu). CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by \> 75 % but still \>1.5 cm in size, and indeterminate bone marrow assessment. Tumor assessments were based on computed tomography (CT) scans with contrast of the neck, chest, and abdomen (if detectable by these techniques) or other diagnostic means, if applicable. Other methods (e.g., MRI) were acceptable for participants in whom contrast CT scans were contraindicated. Due to the limited availability of FDG-PET scanners, an FDG-PET scan was not mandated in the study. |
| Event-free Survival (EFS) | From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years) | EFS was defined as the time from randomization to first occurrence of progression or relapse according to IWG response criteria. IWG criteria is defined using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; partial response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; stable disease (SD): participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease (PD); PD: Lymph nodes considered abnormal if the long axis is more than 1.5 centimeter (cm) regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes less than or equal to (\<=) 1.0 × \<= 1.0 cm would not be considered as abnormal for PD. |
| Disease-free Survival (DFS) | From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years) | DFS was defined as the period from the data of the initial CR/CRu until the date of relapse or death from any cause, whichever occurred first. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) | Randomization of first participant to clinical cutoff date (Up to 4 years) | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Overall Survival (OS) | From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years) | OS was defined as the time from randomization to death from any cause. |
| Percentage of Participants With Anti-Rituximab Antibodies Over Time | Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years) | — |
| Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years) | — |
| Summary of Observed Serum Rituximab Concentration | Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years) | — |
| Progression-free Survival (PFS) | From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years) | PFS was defined as the time from randomization to the first occurrence of progression or relapse, according to the IWG response criteria. IWG criteria is defined criteria using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; PR: At least a 50% decrease in SPD of up to six of the largest dominant nodes or nodal masses; SD: participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD; PD: Lymph nodes considered abnormal if the long axis is more than 1.5 cm regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes \<= 1.0 × \<= 1.0 cm would not be considered as abnormal for PD. |
| Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV]) | Cycle 1-4, Cycle 5-8 for both SC and IV (Up to 32 weeks) | Administration time was defined as the time from start to end of the SC injection or from start to end of the IV infusion |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Croatia, Denmark, Dominican Republic, Egypt, El Salvador, Germany, Guatemala, Hong Kong, Hungary, Indonesia, Italy, Malaysia, Netherlands, New Zealand, Panama, Peru, Philippines, Portugal, Romania, South Korea, Sweden, Taiwan, Thailand, Turkey (Türkiye), Vietnam
Participant flow
Pre-assignment details
A total of 743 participants were enrolled across all the sites and were included in the intent to treat (ITT) population. Three participants were enrolled but died prior to receiving study medication and were not included in the safety population. The Participant Flow represents the safety population.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Participants in Arm A received one cycle of rituximab 375 mg/m\^2 intravenously (IV), then three cycles of rituximab 1400mg subcutaneously (SC), followed by four cycles of rituximab 375 mg/m\^2 IV in combination with a standard chemotherapy of cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone/prednisolone (CHOP), cyclophosphamide, vincristine, prednisone/prednisolone (CVP), or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator. | 371 |
| Arm B Participants in Arm B received four cycles of rituximab 375 mg/m\^2 IV followed by four cycles of rituximab 1400mg SC in combination with a standard chemotherapy of CHOP, CVP, or bendamustine. Rituximab was administered on Day 1 of each treatment cycle followed by administration of the preselected chemotherapy. Cycles were repeated every 14, 21, or 28 days, depending on the combination chemotherapy regimen selected by the investigator. | 369 |
| Total | 740 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 6 |
| Overall Study | Death | 46 | 58 |
| Overall Study | Lost to Follow-up | 15 | 15 |
| Overall Study | Missing | 1 | 1 |
| Overall Study | Participant request/ Withdrew consent | 18 | 14 |
| Overall Study | Reason Not Specified | 36 | 39 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 13.18 | 59.4 years STANDARD_DEVIATION 12.64 | 58.8 years STANDARD_DEVIATION 12.92 |
| Sex: Female, Male Female | 187 Participants | 180 Participants | 367 Participants |
| Sex: Female, Male Male | 184 Participants | 189 Participants | 373 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 318 / 371 | 317 / 369 |
| serious Total, serious adverse events | 126 / 371 | 116 / 369 |
Outcome results
Primary
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6
Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing cycle 6.
Time frame: Cycle 6 (Up to 24 weeks)
Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6 | 79.1 percentage of participants |
| Arm B | Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6 | 80.6 percentage of participants |
Primary
Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8
Participants who preferred rituximab SC over rituximab IV, along with the corresponding 95% confidence interval (CI), were estimated using the patient preference questionnaire (PPQ) after completing Cycle 8.
Time frame: Cycle 8 (Up to 32 weeks)
Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8 | 77.1 percentage of participants |
| Arm B | Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8 | 84.2 percentage of participants |
Secondary
Cancer Therapy Satisfaction Questionnaire (CTSQ) Score
CTSQ is a validated 16-item questionnaire that measures three domains related to participants' satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Time frame: During Cycle 4, 8 of treatment (Up to 32 weeks)
Population: ITT population included all participants who were randomized in the study. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Expectations of therapy domain | 80.88 units on a scale | Standard Deviation 18.315 |
| Arm A | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Feelings about side effects domain | 60.63 units on a scale | Standard Deviation 22.316 |
| Arm A | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Satisfaction with therapy domain | 84.59 units on a scale | Standard Deviation 12.218 |
| Arm B | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Expectations of therapy domain | 82.07 units on a scale | Standard Deviation 17.817 |
| Arm B | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Feelings about side effects domain | 61.64 units on a scale | Standard Deviation 22.324 |
| Arm B | Cancer Therapy Satisfaction Questionnaire (CTSQ) Score | Satisfaction with therapy domain | 85.42 units on a scale | Standard Deviation 11.259 |
Secondary
Complete Response (CR) Rate
CR rate was assessed according to the International Working Group (IWG) Response Criteria (CHESON ET AL. 1999) and included CR and CR unconfirmed (CRu). CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by \> 75 % but still \>1.5 cm in size, and indeterminate bone marrow assessment. Tumor assessments were based on computed tomography (CT) scans with contrast of the neck, chest, and abdomen (if detectable by these techniques) or other diagnostic means, if applicable. Other methods (e.g., MRI) were acceptable for participants in whom contrast CT scans were contraindicated. Due to the limited availability of FDG-PET scanners, an FDG-PET scan was not mandated in the study.
Time frame: 28 days (± 3 days) after Day 1 of the last dose of induction treatment
Population: ITT population included all participants who were randomized in the study. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Complete Response (CR) Rate | 49.2 percentage of participants |
| Arm B | Complete Response (CR) Rate | 52.7 percentage of participants |
Secondary
Disease-free Survival (DFS)
DFS was defined as the period from the data of the initial CR/CRu until the date of relapse or death from any cause, whichever occurred first.
Time frame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
Population: ITT population included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Disease-free Survival (DFS) | NA months |
| Arm B | Disease-free Survival (DFS) | NA months |
Secondary
Event-free Survival (EFS)
EFS was defined as the time from randomization to first occurrence of progression or relapse according to IWG response criteria. IWG criteria is defined using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; partial response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; stable disease (SD): participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for progressive disease (PD); PD: Lymph nodes considered abnormal if the long axis is more than 1.5 centimeter (cm) regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes less than or equal to (\<=) 1.0 × \<= 1.0 cm would not be considered as abnormal for PD.
Time frame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
Population: ITT population included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Event-free Survival (EFS) | NA months |
| Arm B | Event-free Survival (EFS) | NA months |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Randomization of first participant to clinical cutoff date (Up to 4 years)
Population: The safety population included all participants who received at least one dose of rituximab. Number of participants analyzed specifies number of participants who were evaluable for the outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Number of Participants With Treatment Emergent Adverse Events (AEs) | 352 participants |
| Arm B | Number of Participants With Treatment Emergent Adverse Events (AEs) | 347 participants |
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Time frame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
Population: ITT population included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Overall Survival (OS) | NA months |
| Arm B | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time
Time frame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
Population: The safety population included all participants who received at least one dose of rituximab. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 3 | 7.1 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 7 | 23.8 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Interim staging | 9.0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 8 | 13.3 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 2 | 7.0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Final staging | 10.0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 5 | 12.5 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Follow-up, 6 months | 6.5 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 4 | 7.0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Follow-up, 12 months | 7.7 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 6 | 16.0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | End of study/early treatment termination | 3.5 percentage of participants |
| Arm A | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 1 | 11.4 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | End of study/early treatment termination | 6.3 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 1 | 15.6 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 2 | 18.2 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 3 | 23.5 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 4 | 14.7 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Interim staging | 9.7 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 5 | 10.2 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 6 | 11.6 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 7 | 10.9 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Cycle 8 | 11.0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Final staging | 12.6 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Follow-up, 6 months | 13.4 percentage of participants |
| Arm B | Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time | Follow-up, 12 months | 8.7 percentage of participants |
Secondary
Percentage of Participants With Anti-Rituximab Antibodies Over Time
Time frame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
Population: The safety population included all participants who received at least one dose of rituximab. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 3 | 0.3 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 7 | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Interim staging | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 8 | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 2 | 2.1 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Final staging | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 5 | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Follow-up, 6 months | 1.8 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 4 | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Follow-up, 12 months | 2.1 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 6 | 0 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | End of study/early treatment termination | 0.6 percentage of participants |
| Arm A | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 1 | 2.0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | End of study/early treatment termination | 0.6 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 1 | 3.0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 2 | 2.2 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 3 | 0.9 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 4 | 0.3 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Interim staging | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 5 | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 6 | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 7 | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Cycle 8 | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Final staging | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Follow-up, 6 months | 0 percentage of participants |
| Arm B | Percentage of Participants With Anti-Rituximab Antibodies Over Time | Follow-up, 12 months | 0.6 percentage of participants |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of progression or relapse, according to the IWG response criteria. IWG criteria is defined criteria using the following response categories: CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy; PR: At least a 50% decrease in SPD of up to six of the largest dominant nodes or nodal masses; SD: participants fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD; PD: Lymph nodes considered abnormal if the long axis is more than 1.5 cm regardless of the short axis. Lymph node has a long axis of 1.1 to 1.5 cm, it is considered abnormal if its short axis is more than 1.0. Lymph nodes \<= 1.0 × \<= 1.0 cm would not be considered as abnormal for PD.
Time frame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
Population: ITT population included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Progression-free Survival (PFS) | NA months |
| Arm B | Progression-free Survival (PFS) | NA months |
Secondary
Rituximab Administration Satisfaction Questionnaire (RASQ) Score
The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Time frame: During Cycle 4, 8 of treatment (Up to 32 weeks)
Population: ITT population included all participants who were randomized in the study. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Psychological Impact domain | 77.73 units on a scale | Standard Deviation 16.377 |
| Arm A | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Convenience domain | 59.05 units on a scale | Standard Deviation 20.757 |
| Arm A | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Impact on activitiesf daily living | 59.49 units on a scale | Standard Deviation 22.233 |
| Arm A | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Satisfaction domain | 74.88 units on a scale | Standard Deviation 19.349 |
| Arm A | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Physical impact domain | 82.14 units on a scale | Standard Deviation 15.629 |
| Arm B | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Satisfaction domain | 87.26 units on a scale | Standard Deviation 14.972 |
| Arm B | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Physical impact domain | 82.08 units on a scale | Standard Deviation 15.882 |
| Arm B | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Psychological Impact domain | 84.00 units on a scale | Standard Deviation 14.358 |
| Arm B | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Impact on activitiesf daily living | 81.86 units on a scale | Standard Deviation 15.844 |
| Arm B | Rituximab Administration Satisfaction Questionnaire (RASQ) Score | Convenience domain | 81.05 units on a scale | Standard Deviation 13.088 |
Secondary
Summary of Observed Serum Rituximab Concentration
Time frame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
Population: The safety population included all participants who received at least one dose of rituximab. Here, Number Analyzed represents the number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 2 | 25053.1 microgram per milliter | Standard Deviation 19590.17 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 7 | 95614.0 microgram per milliter | Standard Deviation 45499.56 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 4 | 87956.6 microgram per milliter | Standard Deviation 40441.84 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 8 | 104873.0 microgram per milliter | Standard Deviation 50346.69 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 1 | 3355.9 microgram per milliter | Standard Deviation 21600.95 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Final staging | 86806.6 microgram per milliter | Standard Deviation 43005.9 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Interim staging | 117273.6 microgram per milliter | Standard Deviation 52227.06 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Follow-up, 6 months | 7802.9 microgram per milliter | Standard Deviation 15672.57 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 5 | 108030.9 microgram per milliter | Standard Deviation 54335.08 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Follow-up, 12 months | 2380.1 microgram per milliter | Standard Deviation 8494.06 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 3 | 62977.0 microgram per milliter | Standard Deviation 30037.98 |
| Arm A | Summary of Observed Serum Rituximab Concentration | End of study/early treatment termination | 9302.0 microgram per milliter | Standard Deviation 27234.88 |
| Arm A | Summary of Observed Serum Rituximab Concentration | Cycle 6 | 100927.7 microgram per milliter | Standard Deviation 49287.42 |
| Arm B | Summary of Observed Serum Rituximab Concentration | End of study/early treatment termination | 9553.9 microgram per milliter | Standard Deviation 30723.3 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 1 | 970.1 microgram per milliter | Standard Deviation 9415.93 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 2 | 24541.1 microgram per milliter | Standard Deviation 18141.76 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 3 | 46093.9 microgram per milliter | Standard Deviation 31214.3 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 4 | 59485.5 microgram per milliter | Standard Deviation 29183.17 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 5 | 70387.3 microgram per milliter | Standard Deviation 30256.48 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 6 | 98679.7 microgram per milliter | Standard Deviation 40001.55 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 7 | 117172.0 microgram per milliter | Standard Deviation 44501.74 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Cycle 8 | 137048.1 microgram per milliter | Standard Deviation 53669.39 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Final staging | 120995.7 microgram per milliter | Standard Deviation 58731.1 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Follow-up, 6 months | 8042.9 microgram per milliter | Standard Deviation 12247.05 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Follow-up, 12 months | 1685.3 microgram per milliter | Standard Deviation 6669.84 |
| Arm B | Summary of Observed Serum Rituximab Concentration | Interim staging | 77665.3 microgram per milliter | Standard Deviation 29161.77 |
Secondary
Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV])
Administration time was defined as the time from start to end of the SC injection or from start to end of the IV infusion
Time frame: Cycle 1-4, Cycle 5-8 for both SC and IV (Up to 32 weeks)
Population: ITT population included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV]) | 840 minutes |
| Arm B | Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV]) | 22 minutes |