Lymphocytic Leukemia, Chronic
Conditions
Brief summary
This randomized, parallel-group, multi-center study will compare the pharmacokinetics and safety of subcutaneous administration of MabThera (rituximab) versus intravenous MabThera in combination with chemotherapy in previously untreated patients with chronic lymphocytic leukemia (CLL). The study consists of 2 parts. In part 1, patients who have previously received 4 cycles of intravenous MabThera will receive in Cycle 5 intravenous MabThera and in Cycle 6 subcutaneous MabThera. In part 2, patients will be randomized to receive either 6 cycles of intravenous MabThera, or 1 cycle of intravenous MabThera and 5 cycles of subcutaneous MabThera. Additionally, all patients will receive chemotherapy (fludarabine and cyclophosphamide) on Days 1-3 or Days 1-5 of every cycle. The anticipated time on study drug is 24 weeks.
Interventions
DRUGCyclophosphamide
Days 1-3 or Days 1-5 of cycles 1-6
DRUGFludarabine
Days 1-3 or Days 1-5 of cycles 1-6
One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera
Sponsors
Hoffmann-La Roche
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Patients with treatment-requiring chronic lymphocytic leukemia (CLL) * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Life expectancy \>6 months
Exclusion criteria
* Transformation to aggressive B-cell malignancy * History of other malignancy unless the patient was treated with curative intent and has been in remission for more than 5 years prior to enrolment * HIV or Hepatitis B positive unless clearly due to vaccination * Inadequate liver or renal function * Any coexisting medical or psychological condition that would preclude participation in the required study procedures Additional exclusion criterion for Part 1: * Any previous treatment for CLL except for up to 4 cycles of rituximab IV in combination with FC chemotherapy as first-line treatment for CLL Additional exclusion criterion for Part 2: * Any previous treatment for CLL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab | Pre-dose and post-dose (15 minutes to end of infusion) on Day 1 and on Days 2, 5, 11 and 15 of Cycle 5 and Pre-dose, Post-dose on Days 2, 3, 5,11, 15 and 29 of Cycle 6; Pre-dose was taken 2 hours prior rituximab dose | Ctrough is defined as the trough or minimum serum concentration. Pharmacokinetic parameters for rituximab were assessed during Cycles 5 (IV rituximab) and 6 (SC rituximab). Rituximab pharmacokinetic (PK) data from Part 1 were integrated into a population PK model using parametric, nonlinear, mixed-effects modelling. Rituximab IV 500 mg/m\^2 administered once every 4 weeks was compared to fixed doses of rituximab SC between 1400 mg and 1870 mg. The dose selection was performed on Ctrough concentrations at Cycle 5 (pre-dose Cycle 6). A test of the probability of success was applied to each of the 100 replicates, and the percentage of replicates with a positive test corresponded to the probability of success of the trial. |
| Part 2: Rituximab C Trough Levels at Cycle 5 | +/- 25hours around the 28th day post the 5th Cycle of Rituximab administration | Ctrough is defined as the trough or minimum serum concentration in a given cycle of treatment. The objective of Part 2 was to demonstrate the comparability of the observed Ctrough of rituximab SC 1600 mg and rituximab IV 500 mg/m2 at Cycle 5, as assessed by a non-inferiority test with a lower boundary of at least 0.8 for the 90% CI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6 | Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 | Multiple blood samples were obtained at pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab IV arm, and at pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab SC arm and time to peak plasma concentration of rituximab was determined. |
| Part 2: Terminal Half-Life of Rituximab at Cycle 6 | Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 | The terminal half-life (t1/2) of rituximab is defined as the time required for the plasma concentration of rituximab to reach half of its original concentration. |
| Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Days 4 to 5 in Cycle 6 | In part 1 of the trial, upon completion of dosing in cycle 6, participants and their treating nurses were asked whether they have a preference of dosing route, IV vs SC |
| Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Days 4-5 in Cycle 6 | Physicians and nurses who administered rituximab were asked to answer the following question: If used in routine practice, on average, how much staff time could be saved with each administration of rituximab SC as compared to rituximab IV? (Please do not consider the time needed for the first IV administration, consider only the subsequent ones). The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively. |
| Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Days 4-5 in Cycle 6 | Physicians and nurses who administered rituximab were asked to answer the following question: Which formulation of rituximab (SC or IV) do you think is more convenient? with pre-specified responses as below. Percentage of participants with specified answers were reported. The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively. |
| Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6 | Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 | AUC values were calculated by numerical integration using the linear trapezoidal rule. AUC levels were analyzed using the model below: Ln(AUC) = μ + τi + BlTLij + εij wherein, Ln is the natural log, μ denotes the overall mean effect, τi the effect in each treatment group, BlTLij the tumor load at baseline for each patient and εij a random error variable with normal distribution and mean 0. The treatment effect therein was based on a contrast statement in the model to calculate 90 % confidence intervals for ln(AUC SC)- ln(AUC IV). |
| Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Day 0 of Cycle 1 and Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and at each follow-up visit until 24 months after the last dose of rituximab. | In Part 2, samples for the HACA assay were collected at each treatment cycle prior to the administration of rituximab and at each follow-up visit until 24 months after the last dose of rituximab. |
| Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Day 1 of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15,18, 21 and 24 | CD 19 is a surface antigen (protein) present on B-lymphocytes. |
| Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Day 1 pre-dose of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15, 18, 21 and 24 | Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL. |
| Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 1 pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 pre-dose in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit | CD 19 is a surface antigen (protein) present on B-lymphocytes. |
| Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 1 Pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit | Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL. |
| Part 1: Percentage of Participants With Anti-Rituximab Antibodies | Predose at Cycles 5 and 6 and at each follow up visit until 24 months after the last dose | Blood samples for the assessment of antibodies against rituximab (HACAs) were drawn pre-dose at Cycle 5 and Cycle 6 in Part 1 and at each follow up visit until 24 months after the last dose. |
| Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6 | Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 | Cmax was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of rituximab in the blood samplings. |
Countries
Argentina, Australia, Brazil, Canada, Chile, Croatia, Czechia, France, Germany, Greece, Italy, Mexico, New Zealand, Poland, Portugal, Russia, Slovakia, Spain, Turkey (Türkiye)
Participant flow
Pre-assignment details
In Part 1 a single dose of subcutaneous (SC) rituximab was administered at Cycle 6 to select a dose resulting in trough concentration (Ctrough) non-inferior to intravenous (IV) dose. In Part 2, participants were randomized to receive rituximab IV or SC, to demonstrate non-inferiority of rituximab Ctrough levels of SC dose compared with IV dose.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Rituximab SC 1400 Milligrams (mg) Participant could have been enrolled any time during their treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m\^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m\^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m\^2 on Days 1-3 (or as an oral dose of 24 mg/m\^2 on Days 1-5 or 30-40 mg/m\^2 on Days 1-3), and IV cyclophosphamide 250 mg/m\^2 on Days 1-3 (or as an oral dose of 150 mg/m\^2 on Days 1-5 or 200-250 mg/m\^2 on Days 1-3). | 16 |
| Part 1: Rituximab SC 1600 mg Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m\^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m\^2 on Day 1 Cycle 6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m\^2 on Days 1-3 (or as an oral dose of 24 mg/m\^2 on Days 1-5 or 30-40 mg/m\^2 on Days 1-3), and IV cyclophosphamide 250 mg/m\^2 on Days 1-3 (or as an oral dose of 150 mg/m\^2 on Days 1-5 or 200-250 mg/m\^2 on Days 1-3). | 17 |
| Part 1: Rituximab SC 1870 mg Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m\^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m\^2 on Day 1 Cycle 6: SC rituximab 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m\^2 on Days 1-3 (or as an oral dose of 24 mg/m\^2 on Days 1-5 or 30-40 mg/m\^2 on Days 1-3), and IV cyclophosphamide 250 mg/m\^2 on Days 1-3 (or as an oral dose of 150 mg/m\^2 on Days 1-5 or 200-250 mg/m\^2 on Days 1-3). | 22 |
| Part 2 : Rituximab IV 500 mg/m^2 Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m\^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m\^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m\^2 on Days 1-3 (or as an oral dose of 24 mg/m\^2 on Days 1-5 or 30-40 mg/m\^2 on Days 1-3), and IV cyclophosphamide 250 mg/m\^2 on Days 1-3 (or as an oral dose of 150 mg/m\^2 on Days 1-5 or 200-250 mg/m\^2 on Days 1-3). | 89 |
| Part 2: Rituximab SC 1600 mg Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m\^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m\^2 on Days 1-3 (or as an oral dose of 24 mg/m\^2 on Days 1-5 or 30-40 mg/m\^2 on Days 1-3), and IV cyclophosphamide 250 mg/m\^2 on Days 1-3 (or as an oral dose of 150 mg/m\^2 on Days 1-5 or 200-250 mg/m\^2 on Days 1-3). | 85 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Survival Status | Death | 3 | 1 | 3 | 1 | 16 | 10 |
| Part 1: Pilot Dose Selection Period | Adverse Event | 0 | 0 | 0 | 4 | 0 | 0 |
| Part 1: Pilot Dose Selection Period | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Pilot Dose Selection Period | Protocol Violation | 0 | 0 | 0 | 2 | 0 | 0 |
| Part 1: Pilot Dose Selection Period | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Regular Follow-Up Period | Death | 3 | 1 | 3 | 1 | 0 | 0 |
| Part 1: Regular Follow-Up Period | Disease Progression | 3 | 6 | 3 | 0 | 0 | 0 |
| Part 2: Dose Confirmation Period | Adverse Event | 0 | 0 | 0 | 0 | 7 | 9 |
| Part 2: Dose Confirmation Period | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2: Dose Confirmation Period | Physician Decision | 0 | 0 | 0 | 0 | 2 | 0 |
| Part 2: Dose Confirmation Period | Protocol Violation | 0 | 0 | 0 | 0 | 5 | 3 |
| Part 2: Dose Confirmation Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 |
| Part 2: Dose Confirmation Period | Withdrawn Prior to Treatment | 0 | 0 | 0 | 0 | 1 | 1 |
| Part 2: Regular Follow-Up | Adverse Event | 0 | 0 | 0 | 0 | 2 | 2 |
| Part 2: Regular Follow-Up | Death | 0 | 0 | 0 | 0 | 6 | 3 |
| Part 2: Regular Follow-Up | Disease Progression | 0 | 0 | 0 | 0 | 5 | 5 |
| Part 2: Regular Follow-Up | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 1 |
| Part 2: Regular Follow-Up | Noncompliance | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2: Regular Follow-Up | Physician Decision | 0 | 0 | 0 | 0 | 2 | 0 |
| Part 2: Regular Follow-Up | Protocol Violation | 0 | 0 | 0 | 0 | 2 | 0 |
| Part 2: Regular Follow-Up | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 2 : Rituximab IV 500 mg/m^2 | Part 2: Rituximab SC 1600 mg | Total | Part 1: Rituximab SC 1400 Milligrams (mg) | Part 1: Rituximab SC 1600 mg | Part 1: Rituximab SC 1870 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 9.03 | 59.1 years STANDARD_DEVIATION 8.87 | 58.8 years STANDARD_DEVIATION 8.8 | 56.6 years STANDARD_DEVIATION 10.13 | 60.4 years STANDARD_DEVIATION 8.18 | 56.9 years STANDARD_DEVIATION 6.79 |
| Sex: Female, Male Female | 36 Participants | 25 Participants | 76 Participants | 6 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 53 Participants | 60 Participants | 153 Participants | 10 Participants | 15 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 16 | 16 / 17 | 21 / 22 | 1 / 1 | 7 / 8 | 80 / 89 | 81 / 85 |
| serious Total, serious adverse events | 5 / 16 | 8 / 17 | 4 / 22 | 1 / 1 | 3 / 8 | 35 / 89 | 32 / 85 |
Outcome results
Primary
Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab
Ctrough is defined as the trough or minimum serum concentration. Pharmacokinetic parameters for rituximab were assessed during Cycles 5 (IV rituximab) and 6 (SC rituximab). Rituximab pharmacokinetic (PK) data from Part 1 were integrated into a population PK model using parametric, nonlinear, mixed-effects modelling. Rituximab IV 500 mg/m\^2 administered once every 4 weeks was compared to fixed doses of rituximab SC between 1400 mg and 1870 mg. The dose selection was performed on Ctrough concentrations at Cycle 5 (pre-dose Cycle 6). A test of the probability of success was applied to each of the 100 replicates, and the percentage of replicates with a positive test corresponded to the probability of success of the trial.
Time frame: Pre-dose and post-dose (15 minutes to end of infusion) on Day 1 and on Days 2, 5, 11 and 15 of Cycle 5 and Pre-dose, Post-dose on Days 2, 3, 5,11, 15 and 29 of Cycle 6; Pre-dose was taken 2 hours prior rituximab dose
Population: Enrolled (non-randomized) Pharmacokinetic Evaluable Population (Part 1) included all participants from Part 1 who did not significantly violate the inclusion or exclusion criteria, deviate significantly from the protocol or have unavailable or incomplete data which could influence the pharmacokinetic analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Rituximab SC | Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab | 1600 mg |
Primary
Part 2: Rituximab C Trough Levels at Cycle 5
Ctrough is defined as the trough or minimum serum concentration in a given cycle of treatment. The objective of Part 2 was to demonstrate the comparability of the observed Ctrough of rituximab SC 1600 mg and rituximab IV 500 mg/m2 at Cycle 5, as assessed by a non-inferiority test with a lower boundary of at least 0.8 for the 90% CI.
Time frame: +/- 25hours around the 28th day post the 5th Cycle of Rituximab administration
Population: Only participants who entered Part 2 of the study and had pharmacokinetic (PK) data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Rituximab C Trough Levels at Cycle 5 | 61.50 μg/mL | Geometric Coefficient of Variation 89.54 |
| Part 2: Rituximab SC 1600 mg | Part 2: Rituximab C Trough Levels at Cycle 5 | 97.53 μg/mL | Geometric Coefficient of Variation 55.27 |
90% CI: [1.269, 1.852]
Secondary
Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration
In part 1 of the trial, upon completion of dosing in cycle 6, participants and their treating nurses were asked whether they have a preference of dosing route, IV vs SC
Time frame: Days 4 to 5 in Cycle 6
Population: All participants in Part 1 were included in this analysis including 8 participants that did not receive SC rituximab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred SC | 88.0 percentage of participants or nurses |
| Part 1: Rituximab SC | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred IV | 13.0 percentage of participants or nurses |
| Part 1: Rituximab SC | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred SC | 88.0 percentage of participants or nurses |
| Part 1: Rituximab SC | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred IV | 13.0 percentage of participants or nurses |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred IV | 0.0 percentage of participants or nurses |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred SC | 100.0 percentage of participants or nurses |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred SC | 100.0 percentage of participants or nurses |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred IV | 0.0 percentage of participants or nurses |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred IV | 9.0 percentage of participants or nurses |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred IV | 9.0 percentage of participants or nurses |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Nurses who preferred SC | 91.0 percentage of participants or nurses |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration | Participants who preferred SC | 91.0 percentage of participants or nurses |
Secondary
Part 1: Percentage of Participants With Anti-Rituximab Antibodies
Blood samples for the assessment of antibodies against rituximab (HACAs) were drawn pre-dose at Cycle 5 and Cycle 6 in Part 1 and at each follow up visit until 24 months after the last dose.
Time frame: Predose at Cycles 5 and 6 and at each follow up visit until 24 months after the last dose
Population: Safety Analysis Population (SAP): all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. This included 8 participants that did not receive SC rituximab. n = number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Anti-Rituximab Antibodies | Pre-Dose Cycle 5: positive for HACAs (n=59) | 0.0 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Anti-Rituximab Antibodies | Pre-Dose Cycle 5: negative for HACAs (n=59) | 100.0 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Anti-Rituximab Antibodies | Post-Dose: positive for HACAs (n=61) | 5.0 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Anti-Rituximab Antibodies | Post-Dose: negative for HACAs (n=61) | 95.1 percentage of participants |
Secondary
Part 1: Percentage of Participants With Total B-Cell Depletion by Visit
Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL.
Time frame: Day 1 pre-dose of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15, 18, 21 and 24
Population: Part 1 SAP; n = number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 28.6 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 30.8 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=15,1319,1,2) | 93.3 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 93.3 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 86.7 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=12,14,16,0,0) | 25.0 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 30.8 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 93.3 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 93.8 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 53.3 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1(n= 15,14,18,1,0) | 93.3 percentage of participants |
| Part 1: Rituximab SC | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 35.7 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=12,14,16,0,0) | 21.4 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 92.3 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1(n= 15,14,18,1,0) | 100.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 84.6 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=15,1319,1,2) | 92.3 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 50.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 100.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 85.7 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 50.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 100.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 54.5 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 18.8 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=15,1319,1,2) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1(n= 15,14,18,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 94.1 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 60.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 45.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 40.0 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 26.7 percentage of participants |
| Part 1: Rituximab SC 1870 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=12,14,16,0,0) | 18.8 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=15,1319,1,2) | 0.0 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=14,14,20,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=16,8,18,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=14,11,15,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=12,14,16,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=13,14,15,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1(n= 15,14,18,1,0) | 100.0 percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=13,12,16,0,0) | NA percentage of participants |
| Part 1: Rituximab SC 1000 mg | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 100.0 percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=15,13,17,1,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=13,14,15,0,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=15,1319,1,2) | 100.0 percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=14,14,20,0,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1(n= 15,14,18,1,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=15,9,15,1,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=12,14,16,0,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=16,8,18,0,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=14,11,15,0,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=15,13,15,1,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=15,11,19,1,0) | NA percentage of participants |
| Part 1: No SC Dose Received | Part 1: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=13,12,16,0,0) | NA percentage of participants |
Secondary
Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit
CD 19 is a surface antigen (protein) present on B-lymphocytes.
Time frame: Day 1 of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15,18, 21 and 24
Population: Part 1 SAP; n = number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 128 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 66 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 175 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 24 Month Visit(n=12, 4,16,0,0) | 238 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 1 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 2 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 2 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 5 Day 1 (n=15,13,19,1,2) | 2 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 6 Day 1 (n=15,14,18,1,0) | 1 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 3 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 126 cells per microliter (cells/μL) |
| Part 1: Rituximab SC | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 175 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 5 Day 1 (n=15,13,19,1,2) | 3 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 78 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 1 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 24 Month Visit(n=12, 4,16,0,0) | 110 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 19 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 6 Day 1 (n=15,14,18,1,0) | 2 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 2 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 82 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 3 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 41 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 31 cells per microliter (cells/μL) |
| Part 2: Rituximab SC 1600 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 1 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 18 Month Visit (n=13,14,15,0,0) | 189 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 12 Month Visit (n=14,14,20,0,0) | 90 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 6 Day 1 (n=15,14,18,1,0) | 1 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 15 Month Visit (n=14,11,15,0,0) | 106 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 0 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 5 Day 1 (n=15,13,19,1,2) | 0 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 0 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 21 Month Visit (n=13,12,16,0,0) | 149 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 3 Month Visit (n=16,8,18,0,0) | 1 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 24 Month Visit(n=12, 4,16,0,0) | 232 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 2 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1870 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 29 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 28 Day Visit (n=15,11,19,1,0) | 7 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 5 Day 1 (n=15,13,19,1,2) | 84 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 6 Day 1 (n=15,14,18,1,0) | 27 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 21 Month Visit (n=13,12,16,0,0) | NA cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 56 Day Visit (n=15,9,15,1,0) | 14 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 3 Month Visit (n=16,8,18,0,0) | NA cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 6 Month Visit (n=15,13,17,1,0) | 51 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 9 Month Visit (n=15,13,15,1,0) | 74 cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 12 Month Visit (n=14,14,20,0,0) | NA cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 15 Month Visit (n=14,11,15,0,0) | NA cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 18 Month Visit (n=13,14,15,0,0) | NA cells per microliter (cells/μL) |
| Part 1: Rituximab SC 1000 mg | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 24 Month Visit(n=12, 4,16,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 9 Month Visit (n=15,13,15,1,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 24 Month Visit(n=12, 4,16,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 18 Month Visit (n=13,14,15,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 6 Month Visit (n=15,13,17,1,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 3 Month Visit (n=16,8,18,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 56 Day Visit (n=15,9,15,1,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 21 Month Visit (n=13,12,16,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 28 Day Visit (n=15,11,19,1,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 6 Day 1 (n=15,14,18,1,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | Cycle 5 Day 1 (n=15,13,19,1,2) | 2 cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 15 Month Visit (n=14,11,15,0,0) | NA cells per microliter (cells/μL) |
| Part 1: No SC Dose Received | Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit | FU 12 Month Visit (n=14,14,20,0,0) | NA cells per microliter (cells/μL) |
Secondary
Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6
Cmax was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of rituximab in the blood samplings.
Time frame: Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6
Population: Only participants who entered Part 2 of the study and had PK data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6 | 279.78 μg/mL | Geometric Coefficient of Variation 23.96 |
| Part 2: Rituximab SC 1600 mg | Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6 | 202.16 μg/mL | Geometric Coefficient of Variation 36.1 |
90% CI: [0.653, 0.792]
Secondary
Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6
AUC values were calculated by numerical integration using the linear trapezoidal rule. AUC levels were analyzed using the model below: Ln(AUC) = μ + τi + BlTLij + εij wherein, Ln is the natural log, μ denotes the overall mean effect, τi the effect in each treatment group, BlTLij the tumor load at baseline for each patient and εij a random error variable with normal distribution and mean 0. The treatment effect therein was based on a contrast statement in the model to calculate 90 % confidence intervals for ln(AUC SC)- ln(AUC IV).
Time frame: Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6
Population: Only participants who entered Part 2 of the study and had PK data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6 | 3630.43 μg*day/mL | Geometric Coefficient of Variation 38.61 |
| Part 2: Rituximab SC 1600 mg | Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6 | 4088.78 μg*day/mL | Geometric Coefficient of Variation 37.52 |
90% CI: [0.979, 1.242]
Secondary
Part 2: Percentage of Participants With Anti-Rituximab Antibodies
In Part 2, samples for the HACA assay were collected at each treatment cycle prior to the administration of rituximab and at each follow-up visit until 24 months after the last dose of rituximab.
Time frame: Day 0 of Cycle 1 and Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and at each follow-up visit until 24 months after the last dose of rituximab.
Population: SAP; n = number of participants analyzed for the specific parameter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Baseline pre Cycle 1: positive for HACAs (n=87,85) | 0.0 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Baseline pre Cycle 1: negative for HACAs (n=87,85) | 100.0 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Post-Baseline: positive for HACAs (n=89,85) | 15.0 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Post-Baseline: negative for HACAs (n=89,85) | 85.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Post-Baseline: negative for HACAs (n=89,85) | 88.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Baseline pre Cycle 1: positive for HACAs (n=87,85) | 2.4 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Post-Baseline: positive for HACAs (n=89,85) | 12.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Anti-Rituximab Antibodies | Baseline pre Cycle 1: negative for HACAs (n=87,85) | 97.6 percentage of participants |
Secondary
Part 2: Percentage of Participants With Total B-Cell Depletion by Visit
Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL.
Time frame: Cycle 1 Pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit
Population: Part 2 SAP; n= number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 - Post-dose (n=65, 66) | 32.3 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=63,67) | 92.1 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 3 Day 1 (n=67,68) | 73.1 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=67,67) | 95.5 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 - Pre-dose (n=71, 74) | 23.9 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=60,69) | 88.3 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 4 Day 1 (n=71,69) | 83.1 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=65,64) | 66.2 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=60,61) | 43.3 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 Day 2 (n=54, 59) | 35.2 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=59,60) | 33.9 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=68,67) | 88.2 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=57,58) | 24.6 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 1 - Baseline (n=80,80)) | 0.0 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=55,52) | 14.5 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1 (n=71,64) | 95.8 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=56,51) | 10.7 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 Day 3 (n=48, 54) | 50.0 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Withdrawn/Termination (n=17,15) | 41.2 percentage of participants |
| Part 1: Rituximab SC | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=66,64) | 95.5 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Withdrawn/Termination (n=17,15) | 73.3 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 1 - Baseline (n=80,80)) | 0.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 - Pre-dose (n=71, 74) | 31.1 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 - Post-dose (n=65, 66) | 37.9 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 Day 2 (n=54, 59) | 30.5 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 2 Day 3 (n=48, 54) | 37.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 3 Day 1 (n=67,68) | 76.5 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 4 Day 1 (n=71,69) | 84.1 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 5 Day 1 (n=68,67) | 89.6 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | Cycle 6 Day 1 (n=71,64) | 95.3 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 28 Day Visit (n=66,64) | 96.9 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 56 Day Visit (n=63,67) | 97.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 3 Month Visit (n=67,67) | 92.5 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 6 Month Visit (n=60,69) | 91.3 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 12 Month Visit (n=60,61) | 42.6 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 15 Month Visit (n=59,60) | 30.0 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 18 Month Visit (n=57,58) | 25.9 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 21 Month Visit (n=55,52) | 19.2 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 24 Month Visit (n=56,51) | 15.7 percentage of participants |
| Part 2: Rituximab SC 1600 mg | Part 2: Percentage of Participants With Total B-Cell Depletion by Visit | FU 9 Month Visit (n=65,64) | 70.3 percentage of participants |
Secondary
Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV
Physicians and nurses who administered rituximab were asked to answer the following question: Which formulation of rituximab (SC or IV) do you think is more convenient? with pre-specified responses as below. Percentage of participants with specified answers were reported. The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.
Time frame: Days 4-5 in Cycle 6
Population: All the physicians and nurses who responded to the questionnaire were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab SC is much more convenient | 81.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab SC is a little more convenient | 7.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Both formulations are equally convenient | 9.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab IV is a little more convenient | 3.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab IV is much more convenient | 0.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab SC is much more convenient | 78.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab SC a little more convenient | 15.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Both formulations equally convenient | 6.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab IV a little more convenient | 0.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab IV is much more convenient | 0.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Both formulations equally convenient | 6.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab SC is much more convenient | 77.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab SC is much more convenient | 80.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab SC is a little more convenient | 9.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab IV is much more convenient | 0.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Both formulations are equally convenient | 4.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab SC a little more convenient | 14.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab IV is a little more convenient | 10.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Physician: Rituximab IV a little more convenient | 0.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV | Nurse: Rituximab IV is much more convenient | 0.0 percentage of participants in the survey |
Secondary
Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV
Physicians and nurses who administered rituximab were asked to answer the following question: If used in routine practice, on average, how much staff time could be saved with each administration of rituximab SC as compared to rituximab IV? (Please do not consider the time needed for the first IV administration, consider only the subsequent ones). The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.
Time frame: Days 4-5 in Cycle 6
Population: All the physicians and nurses who responded to the questionnaire were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: 4 or more hours | 21.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 3 hours but less than 4 hours | 23.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 2 hours but less than 3 hours | 26.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 1 hour but less than 2 hours | 17.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: Less than 1 hour | 13.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: 4 or more hours | 21.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 3 hours but less than 4 hours | 18.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 2 hours but less than 3 hours | 24.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 1 hour but less than 2 hours | 22.0 percentage of participants in the survey |
| Part 1: Rituximab SC | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: Less than 1 hour | 10.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 2 hours but less than 3 hours | 26.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: 4 or more hours | 21.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: 4 or more hours | 22.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 3 hours but less than 4 hours | 29.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: Less than 1 hour | 7.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 2 hours but less than 3 hours | 23.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 3 hours but less than 4 hours | 21.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: At least 1 hour but less than 2 hours | 11.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Physician: At least 1 hour but less than 2 hours | 19.0 percentage of participants in the survey |
| Part 2: Rituximab SC 1600 mg | Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV | Nurse: Less than 1 hour | 16.0 percentage of participants in the survey |
Secondary
Part 2: Terminal Half-Life of Rituximab at Cycle 6
The terminal half-life (t1/2) of rituximab is defined as the time required for the plasma concentration of rituximab to reach half of its original concentration.
Time frame: Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6
Population: Only participants who entered Part 2 of the study and had PK data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Terminal Half-Life of Rituximab at Cycle 6 | 30.09 days | Geometric Coefficient of Variation 41.86 |
| Part 2: Rituximab SC 1600 mg | Part 2: Terminal Half-Life of Rituximab at Cycle 6 | 30.71 days | Geometric Coefficient of Variation 33.19 |
90% CI: [0.895, 1.139]
Secondary
Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6
Multiple blood samples were obtained at pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab IV arm, and at pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab SC arm and time to peak plasma concentration of rituximab was determined.
Time frame: Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6
Population: Only participants who entered Part 2 of the study and had PK data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6 | 0.22 days | Geometric Coefficient of Variation 130.84 |
| Part 2: Rituximab SC 1600 mg | Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6 | 3.14 days | Geometric Coefficient of Variation 87.62 |
90% CI: [11.215, 19.755]
Secondary
Part 2: Total CD19+ B-Cell Counts by Visit
CD 19 is a surface antigen (protein) present on B-lymphocytes.
Time frame: Cycle 1 pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 pre-dose in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit
Population: Part 2 SAP; n = number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 56 Day Visit (n=63,67) | 2 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 3 Day 1 (n=67,68) | 12 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 3 Month Visit (n=67,67) | 2 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 - Post-dose (n=65, 66) | 163 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 6 Month Visit (n=60,69) | 3 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 4 Day 1 (n=71,69) | 4 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 9 Month Visit (n=65,64) | 35 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 - Pre-dose (n=71,74) | 338 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 12 Month Visit (n=60,61) | 91 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 5 Day 1 (n=68,67) | 2 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 15 Month Visit (n=59,60) | 135 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 Day 2 (n=54, 59) | 154 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 18 Month Visit (n=57,58) | 134 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 6 Day 1 (n=71,64) | 3 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 21 Month Visit (n=55,52) | 171 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 Day 3 (n=48, 54) | 87 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 24 Month Visit (n=56,51) | 214 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | FU 28 Day Visit (n=66,64) | 2 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Withdrawn/Termination (n=17,15) | 150 cells/μL |
| Part 1: Rituximab SC | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 1 - Baseline (n=80,80) | 68905 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Withdrawn/Termination (n=17,15) | 6 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 1 - Baseline (n=80,80) | 50565 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 - Pre-dose (n=71,74) | 253 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 - Post-dose (n=65, 66) | 168 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 Day 3 (n=48, 54) | 125 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 3 Day 1 (n=67,68) | 8 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 4 Day 1 (n=71,69) | 4 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 5 Day 1 (n=68,67) | 2 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 6 Day 1 (n=71,64) | 3 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 28 Day Visit (n=66,64) | 2 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 56 Day Visit (n=63,67) | 2 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 3 Month Visit (n=67,67) | 2 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 6 Month Visit (n=60,69) | 3 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 9 Month Visit (n=65,64) | 30 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 12 Month Visit (n=60,61) | 104 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 15 Month Visit (n=59,60) | 171 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 18 Month Visit (n=57,58) | 223 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 21 Month Visit (n=55,52) | 277 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | FU 24 Month Visit (n=56,51) | 256 cells/μL |
| Part 2: Rituximab SC 1600 mg | Part 2: Total CD19+ B-Cell Counts by Visit | Cycle 2 Day 2 (n=54, 59) | 266 cells/μL |