Lymphoma
Conditions
Brief summary
This single arm, multicenter study will evaluate the safety, efficacy and pharmacokinetic (PK) of subcutaneous (SC) rituximab in previously untreated participants with cluster of differentiation 20 positive (CD20+) DLBCL or FL. In addition to standard chemotherapy, participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period.
Interventions
DRUGRituximab
Rituximab will be administered at a dose of 1400 mg SC once a month for at least 4 doses during the Induction period, and at a dose of 1400 mg SC once every two months for at least 6 doses during the Maintenance period.
DRUGCyclophosphamide
Cyclophosphamide will be administered as per standard local practice as a part of standard chemotherapy regimen.
DRUGVincristine
Vincristine will be administered as per standard local practice as a part of standard chemotherapy regimen.
DRUGDoxorubicin
Doxorubicin will be administered as per standard local practice as a part of standard chemotherapy regimen.
DRUGPrednisone
Prednisone will be administered as per standard local practice as a part of standard chemotherapy regimen.
DRUGBendamustine
Bendamustine will be administered as per standard local practice as a part of standard chemotherapy regimen.
Sponsors
Hoffmann-La Roche
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, CD20+ DLBCL or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2 or 3a, according to the World Health Organization (WHO) classification system * Currently being treated with rituximab intravenously (IV) in the Induction or Maintenance period, 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 (i.e. tolerability issues) * Expectation and current ability for the participant to receive at least 4 additional cycles of treatment during the Induction period or 6 additional cycles of treatment during the Maintenance period (participants with follicular NHL) * An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion greater than or equal to (\>=) 7.5 centimeters (cm), or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) assessed before the first rituximab IV administration in Induction period * At least one bi-dimensionally measurable lesion defined as \>=1.5 cm in its largest dimension on computed tomography (CT) scan * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 3
Exclusion criteria
* Transformed lymphoma or FL IIIB * Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL * History of other malignancy * Ongoing corticosteroid use greater than (\>) 30 milligrams per day (mg/day) of prednisone or equivalent * 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 * Contraindications to any of the individual components of standard chemotherapy * Other serious underlying medical conditions, which, in the Investigator's judgement, could impair the ability of the participant to participate in the study * Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis) * Active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or human immunodeficiency virus (HIV) infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Administration-Associated Reactions (AAR) | Baseline up to 54 months | AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs) | Baseline up to 54 months | Grading of IIRRs was completed according to the CTCAE, version 4.0. |
| Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events | Baseline up to 54 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. |
| Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria | Day 1 up to first occurrence of progression or relapse, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first (up to maximum 54 months) | EFS was defined as the time from first dose of rituximab to first occurrence of progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurred first. |
| Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria | Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months) | PFS was defined as the time from first dose of rituximab to the first occurrence of disease progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or death from any cause, whichever occurred first. |
| Percentage of Participants With Overall Survival (OS) | Day 1 until death (up to maximum 54 months) | OS was defined as the time from first dose of rituximab to death from any cause. |
| Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria | From 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occurs first (up to maximum 54 months) (end of Induction period = up to 8 months) | DFS assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occured first. |
| Percentage of Participants With Complete Response (CR) According to IWG Response Criteria | At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months) | Complete response required: 1) the complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities, 2) all lymph nodes and nodal masses had regressed to normal size, 3) the spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and not be palpable on physical examination and 4) if the bone marrow was involved by lymphoma before treatment, the infiltrate was cleared on repeat bone marrow aspirate and biopsy of the same site. CR/unconfirmed (CRu) included those patients who fulfilled criteria 1 and 3 above as well as 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that regressed by more than 75% in the SPD and 2) indeterminate bone marrow. Response was assessed according to the IWG response criteria. |
| FL: Plasma Trough Concentrations of Rituximab | Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 | FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Pharmacokinetic (PK) data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days. |
| FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab | Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 | FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days. |
| Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) | Baseline up to 54 months | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore 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 worsened during the study were also considered as adverse events. Grading was completed according to the CTCAE, version 4.0. |
| DLBCL: Plasma Concentrations of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 pre-dose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Apparent Total Clearance (CL/F) of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1 | Plasma concentrations of rituximab in participants with DLBCL by chemotherapy regimen cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 14 days (R-CHOP-14) or cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 21 days (R-CHOP-21) in the PK) population.DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days. |
| Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | DLBCL: Cycle (C) 2, C3, C4, C5, C6, End of C8; FL: Induction: C3, C4, C5, C6, C8, Maintenance: C2, C3, C4, C5, C6, C7, C8, C10, C12, End of treatment (4-8 weeks after last dose) | Patient-assessed satisfaction was evaluated using RASQ. Participants were asked questions regarding convenience and satisfaction for rituximab SC. 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. DLBCL participants could be enrolled at cycle 2, cycle 3, or cycle 4. FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must be able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Each Cycle is 21 days for DLBCL. Each Cycle 21 days during the Induction phase and 2 months during Maintenance phase for FL. |
| FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1 | FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days. |
Countries
Italy
Participant flow
Recruitment details
The study was conducted at 37 investigational centers in Italy.
Pre-assignment details
Total overall participants enrolled in the study was 159, however for the subject disposition and baseline characteristics the enrolled was 158 as one participant discontinued the study prior to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) Participants with DLBCL, who had received at least 4 doses of rituximab 1400 mg SC once a month during the treatment phase, up to a maximum of 7 cycles, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); as per standard local practice. | 72 |
| Follicular Lymphoma (FL) Participants with CD20+ non-Hodgkin's (FL), who had received at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period, in addition to standard chemotherapy. Standard chemotherapy regimen included cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP); or cyclophosphamide, vincristine and prednisone (CVP); or bendamustine as per standard local practice. | 86 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Consent Withdrawal | 3 |
| Overall Study | Death | 18 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Other | 4 |
| Overall Study | Progression of Disease | 14 |
Baseline characteristics
| Characteristic | Diffuse Large B-Cell Lymphoma (DLBCL) | Follicular Lymphoma (FL) | Total |
|---|---|---|---|
| Age, Continuous Intent-to-Treat Population | 59.7 years STANDARD_DEVIATION 12.7 | 57.8 years STANDARD_DEVIATION 9.92 | 58.7 years STANDARD_DEVIATION 11.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 72 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 28 Participants | 44 Participants | 72 Participants |
| Sex: Female, Male Male | 44 Participants | 42 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 72 | 4 / 86 |
| other Total, other adverse events | 50 / 72 | 56 / 86 |
| serious Total, serious adverse events | 26 / 72 | 23 / 86 |
Outcome results
Primary
Percentage of Participants With Administration-Associated Reactions (AAR)
AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab 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: Baseline up to 54 months
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Administration-Associated Reactions (AAR) | At least One AAR | 4.2 Percentage of Participants |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Administration-Associated Reactions (AAR) | At Least One AAR Grade ≥3 | 0 Percentage of Participants |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Localized) | 1.4 Percentage of Participants |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Non-Localized) | 2.8 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Non-Localized) | 0 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Administration-Associated Reactions (AAR) | At least One AAR | 8.1 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Localized) | 8.1 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Administration-Associated Reactions (AAR) | At Least One AAR Grade ≥3 | 0 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Non-Localized) | 1.3 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Administration-Associated Reactions (AAR) | At Least One AAR Grade ≥3 | 0 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Administration-Associated Reactions (AAR) | Cutaneous and Soft Tissue AARs (Localized) | 5.1 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Administration-Associated Reactions (AAR) | At least One AAR | 6.3 Percentage of Participants |
Secondary
DLBCL: Apparent Total Clearance (CL/F) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: PK evaluable population. CL/F was not estimable for available PK concentrations in DLBCL participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Apparent Total Clearance (CL/F) of Rituximab | NA liter per hour (L/h) |
Secondary
DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: PK evaluable population. AUC was not estimable for available PK concentrations in DLBCL participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab | NA mcg*hr/mL |
Secondary
DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: PK evaluable population. Cmax was not estimable for available PK concentrations in DLBCL participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab | NA micrograms per millilitre (ug/mL) |
Secondary
DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: The overall geometric LS mean plasma trough concentrations of rituximab in participants with DLBCL in the PK population. The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab | 70.50 micrograms per millilitre (ug/mL) |
Secondary
DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21
Plasma concentrations of rituximab in participants with DLBCL by chemotherapy regimen cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 14 days (R-CHOP-14) or cyclophosphamide, oncovine (vincristine), doxorubicin, prednisone/prednisolone given every 21 days (R-CHOP-21) in the PK) population.DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: DLBCL: R-CHOP 21 or R-CHOP-14; The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 2 Predose | 170.00 micrograms per millilitre (ug/mL) | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 5 Predose | 125.00 micrograms per millilitre (ug/mL) | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Baseline | 214.25 micrograms per millilitre (ug/mL) | Standard Deviation 233.493 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Predose | 93.50 micrograms per millilitre (ug/mL) | Standard Deviation 79.903 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Day 7 | 71.55 micrograms per millilitre (ug/mL) | Standard Deviation 26.092 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Day 14 | 42.00 micrograms per millilitre (ug/mL) | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 8 Predose | 78.50 micrograms per millilitre (ug/mL) | Standard Deviation 14.849 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Baseline | 74.25 micrograms per millilitre (ug/mL) | Standard Deviation 77.064 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 8 Predose | 123.76 micrograms per millilitre (ug/mL) | Standard Deviation 92.606 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Predose | 150.13 micrograms per millilitre (ug/mL) | Standard Deviation 126.221 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 2 Predose | 28.37 micrograms per millilitre (ug/mL) | Standard Deviation 22.695 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 3 Predose | 88.92 micrograms per millilitre (ug/mL) | Standard Deviation 92.79 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 4 Predose | 110.50 micrograms per millilitre (ug/mL) | Standard Deviation 101.116 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Day 14 | 272.50 micrograms per millilitre (ug/mL) | Standard Deviation 103.722 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 5 Predose | 94.00 micrograms per millilitre (ug/mL) | Standard Deviation 48.806 |
| Follicular Lymphoma (FL) | DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21 | Cycle 7 Day 7 | 398.76 micrograms per millilitre (ug/mL) | Standard Deviation 517.974 |
Secondary
DLBCL: Plasma Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 2 Predose | 42.53 micrograms per millilitre (ug/mL) | Standard Deviation 49.637 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 3 Predose | 88.92 micrograms per millilitre (ug/mL) | Standard Deviation 92.79 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 4 Predose | 110.50 micrograms per millilitre (ug/mL) | Standard Deviation 101.116 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 5 Predose | 100.20 micrograms per millilitre (ug/mL) | Standard Deviation 44.483 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Baseline | 92.92 micrograms per millilitre (ug/mL) | Standard Deviation 114.466 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 7 Predose | 141.44 micrograms per millilitre (ug/mL) | Standard Deviation 122.314 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 7 Day 7 | 348.81 micrograms per millilitre (ug/mL) | Standard Deviation 490.785 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 7 Day 14 | 226.40 micrograms per millilitre (ug/mL) | Standard Deviation 136.729 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Concentrations of Rituximab | Cycle 8 Predose | 117.61 micrograms per millilitre (ug/mL) | Standard Deviation 89.394 |
Secondary
DLBCL: Plasma Trough Concentrations of Rituximab
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 pre-dose on Day 1
Population: The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 2 Predose | 42.53 micrograms per millilitre (ug/mL) | Standard Deviation 49.637 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 3 Predose | 88.92 micrograms per millilitre (ug/mL) | Standard Deviation 92.79 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 4 Predose | 110.50 micrograms per millilitre (ug/mL) | Standard Deviation 101.116 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 5 Predose | 100.20 micrograms per millilitre (ug/mL) | Standard Deviation 44.483 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Baseline | 92.92 micrograms per millilitre (ug/mL) | Standard Deviation 114.466 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 7 Predose | 141.44 micrograms per millilitre (ug/mL) | Standard Deviation 122.314 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab | Cycle 8 Predose | 117.61 micrograms per millilitre (ug/mL) | Standard Deviation 89.394 |
Secondary
DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
DLBCL participants received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC; therefore DLBCL participants could be enrolled at Cycle 2, Cycle 3, Cycle 4, or Cycle 5 and as a result the baseline PK sample could be collected at Cycle 2, Cycle 3, Cycle 4, or Cycle 5. Each Cycle is 21 days.
Time frame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
Population: DLBCL participants with Complete Response/Complete Response Unconfirmed (CR/CRu). The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 2 Predose | 53.97 micrograms per millilitre (ug/mL) | Standard Deviation 56.169 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 3 Predose | 101.79 micrograms per millilitre (ug/mL) | Standard Deviation 101.223 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 4 Predose | 110.50 micrograms per millilitre (ug/mL) | Standard Deviation 101.116 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 5 Predose | 121.67 micrograms per millilitre (ug/mL) | Standard Deviation 45.092 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Baseline | 109.40 micrograms per millilitre (ug/mL) | Standard Deviation 125.603 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 7 Predose | 157.93 micrograms per millilitre (ug/mL) | Standard Deviation 131.178 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 8 Predose | 132.57 micrograms per millilitre (ug/mL) | Standard Deviation 95.447 |
Secondary
FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time frame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Population: The overall geometric LS mean plasma trough concentrations of rituximab in participants with FL in the pharmacokinetic (PK) population. The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab | 61.01 micrograms per millilitre (ug/mL) |
Secondary
FL: Plasma Trough Concentrations of Rituximab
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Pharmacokinetic (PK) data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time frame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Population: The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Cycle 2 Predose | 55.49 micrograms per millilitre (ug/mL) | Standard Deviation 64.275 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Cycle 3 Predose | 119.50 micrograms per millilitre (ug/mL) | Standard Deviation 139.606 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Cycle 4 Predose | 157.25 micrograms per millilitre (ug/mL) | Standard Deviation 132.583 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Cycle 5 Predose | 7.60 micrograms per millilitre (ug/mL) | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Baseline | 90.88 micrograms per millilitre (ug/mL) | Standard Deviation 107.089 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab | Cycle 8 Predose | 201.56 micrograms per millilitre (ug/mL) | Standard Deviation 372.609 |
Secondary
FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must have been able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. PK data only collected for participants enrolled during Induction. During the induction phase each Cycle is 21 days.
Time frame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
Population: FL participants with Complete Response/Complete Response Unconfirmed (CR/CRu). The number analyzed includes participants who were evaluable at each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 2 Predose | 48.86 micrograms per millilitre (ug/mL) | Standard Deviation 57.64 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 3 Predose | 156.33 micrograms per millilitre (ug/mL) | Standard Deviation 193.753 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 4 Predose | 200.33 micrograms per millilitre (ug/mL) | Standard Deviation 123.411 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 5 Predose | 7.60 micrograms per millilitre (ug/mL) | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Baseline | 97.90 micrograms per millilitre (ug/mL) | Standard Deviation 118.897 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu) | Cycle 8 Predose | 284.08 micrograms per millilitre (ug/mL) | Standard Deviation 504.113 |
Secondary
Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs)
Grading of IIRRs was completed according to the CTCAE, version 4.0.
Time frame: Baseline up to 54 months
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs) | 0 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs) | 0 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs) | 0 Percentage of Participants |
Secondary
Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore 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 worsened during the study were also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.
Time frame: Baseline up to 54 months
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) | 51.4 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) | 43.0 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs) | 46.8 Percentage of Participants |
Secondary
Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events
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: Baseline up to 54 months
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events | 36.1 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events | 26.7 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events | 31.0 Percentage of Participants |
Secondary
Percentage of Participants With Complete Response (CR) According to IWG Response Criteria
Complete response required: 1) the complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities, 2) all lymph nodes and nodal masses had regressed to normal size, 3) the spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and not be palpable on physical examination and 4) if the bone marrow was involved by lymphoma before treatment, the infiltrate was cleared on repeat bone marrow aspirate and biopsy of the same site. CR/unconfirmed (CRu) included those patients who fulfilled criteria 1 and 3 above as well as 1) a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that regressed by more than 75% in the SPD and 2) indeterminate bone marrow. Response was assessed according to the IWG response criteria.
Time frame: At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months)
Population: ITT population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Complete Response (CR) According to IWG Response Criteria | 65.2 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Complete Response (CR) According to IWG Response Criteria | 67.9 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Complete Response (CR) According to IWG Response Criteria | 66.4 Percentage of Participants |
Secondary
Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria
DFS assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occured first.
Time frame: From 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occurs first (up to maximum 54 months) (end of Induction period = up to 8 months)
Population: ITT population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria | 21.7 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria | 25.6 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria | 23.5 Percentage of Participants |
Secondary
Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria
EFS was defined as the time from first dose of rituximab to first occurrence of progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurred first.
Time frame: Day 1 up to first occurrence of progression or relapse, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first (up to maximum 54 months)
Population: ITT population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria | 29.2 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria | 22.1 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria | 25.3 Percentage of Participants |
Secondary
Percentage of Participants With Overall Survival (OS)
OS was defined as the time from first dose of rituximab to death from any cause.
Time frame: Day 1 until death (up to maximum 54 months)
Population: ITT population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Overall Survival (OS) | 19.4 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Overall Survival (OS) | 4.7 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Overall Survival (OS) | 11.4 Percentage of Participants |
Secondary
Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria
PFS was defined as the time from first dose of rituximab to the first occurrence of disease progression or relapse, according to the International Working Group (IWG) response criteria or other country standards, or death from any cause, whichever occurred first.
Time frame: Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months)
Population: ITT population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria | 29.2 Percentage of Participants |
| Follicular Lymphoma (FL) | Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria | 22.1 Percentage of Participants |
| Subcutaneous (SC) Rituximab | Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria | 25.3 Percentage of Participants |
Secondary
Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores
Patient-assessed satisfaction was evaluated using RASQ. Participants were asked questions regarding convenience and satisfaction for rituximab SC. 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. DLBCL participants could be enrolled at cycle 2, cycle 3, or cycle 4. FL participants could be enrolled during induction or maintenance phase and they should have received at least 1 infusion of rituximab and must be able to receive at least 4 cycles of rituximab SC if enrolled during induction or 4 cycles of rituximab SC if enrolled during maintenance. Each Cycle is 21 days for DLBCL. Each Cycle 21 days during the Induction phase and 2 months during Maintenance phase for FL.
Time frame: DLBCL: Cycle (C) 2, C3, C4, C5, C6, End of C8; FL: Induction: C3, C4, C5, C6, C8, Maintenance: C2, C3, C4, C5, C6, C7, C8, C10, C12, End of treatment (4-8 weeks after last dose)
Population: Safety population included all enrolled patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 6 Treatment | 84.6 Units on a Scale | Standard Deviation 14.57 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 8 Treatment | 91.2 Units on a Scale | Standard Deviation 12.76 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 5 Treatment | 83.3 Units on a Scale | Standard Deviation 9.96 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 6 Treatment | 80.8 Units on a Scale | Standard Deviation 9.85 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 8 Treatment | 83.8 Units on a Scale | Standard Deviation 11.6 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 2 Treatment | 75.0 Units on a Scale | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 3 Treatment | 81.9 Units on a Scale | Standard Deviation 10.28 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 4 Treatment | 82.1 Units on a Scale | Standard Deviation 12.17 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 2 Treatment | 87.5 Units on a Scale | — |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 3 Treatment | 83.3 Units on a Scale | Standard Deviation 11.53 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 4 Treatment | 85.6 Units on a Scale | Standard Deviation 13.62 |
| Diffuse Large B-Cell Lymphoma (DLBCL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 5 Treatment | 83.3 Units on a Scale | Standard Deviation 8.84 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 10 Maintenance | 91.7 Units on a Scale | — |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 12 Maintenance | 86.3 Units on a Scale | Standard Deviation 12.69 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain End of Treatment | 75.0 Units on a Scale | Standard Deviation 16.67 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 3 Induction | 89.4 Units on a Scale | Standard Deviation 10.23 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 4 Induction | 84.1 Units on a Scale | Standard Deviation 13.8 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 5 Induction | 91.7 Units on a Scale | Standard Deviation 8.84 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 6 Induction | 93.8 Units on a Scale | Standard Deviation 8.84 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 8 Induction | 91.3 Units on a Scale | Standard Deviation 9.47 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 2 Maintenance | 92.0 Units on a Scale | Standard Deviation 9.28 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 3 Maintenance | 79.2 Units on a Scale | Standard Deviation 20.41 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 4 Maintenance | 100.0 Units on a Scale | — |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 5 Maintenance | 79.7 Units on a Scale | Standard Deviation 16.28 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 6 Maintenance | 87.5 Units on a Scale | Standard Deviation 17.68 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 7 Maintenance | 94.2 Units on a Scale | Standard Deviation 9 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 8 Maintenance | 93.8 Units on a Scale | Standard Deviation 7.22 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 10 Maintenance | 50.0 Units on a Scale | — |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain Cycle 12 Maintenance | 91.0 Units on a Scale | Standard Deviation 13.21 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 3 Induction | 81.8 Units on a Scale | Standard Deviation 8.66 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Satisfaction domain End of Treatment | 75.0 Units on a Scale | Standard Deviation 21.65 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 4 Induction | 76.5 Units on a Scale | Standard Deviation 6.26 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 5 Induction | 79.6 Units on a Scale | Standard Deviation 10.3 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 6 Induction | 95.8 Units on a Scale | Standard Deviation 5.89 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 8 Induction | 83.1 Units on a Scale | Standard Deviation 9.18 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 2 Maintenance | 83.6 Units on a Scale | Standard Deviation 8.71 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 3 Maintenance | 87.5 Units on a Scale | Standard Deviation 19.54 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 4 Maintenance | 100.0 Units on a Scale | Standard Deviation 0 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 5 Maintenance | 80.2 Units on a Scale | Standard Deviation 12.55 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 6 Maintenance | 83.3 Units on a Scale | Standard Deviation 16.67 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 7 Maintenance | 82.7 Units on a Scale | Standard Deviation 12.59 |
| Follicular Lymphoma (FL) | Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores | Convenience domain Cycle 8 Maintenance | 93.8 Units on a Scale | Standard Deviation 12.5 |