Non-Hodgkin's Lymphoma
Conditions
Brief summary
This study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy of ocrelizumab in participants with progressive follicular NHL.
Interventions
DRUGOcrelizumab
Participants will receive a total of 8 intravenous (IV) infusions of ocrelizumab given at intervals of 3 weeks, until disease progression or unacceptable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Follicular NHL * Documented history of response, or stable disease more than 6 months in duration, to a rituximab-containing regimen that was the last treatment before enrollment in the study * No evidence of hepatitis B or C
Exclusion criteria
* Prior monoclonal antibody therapy other than rituximab, anti-cancer vaccine, or radioimmunotherapy for cancer * History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products * Major nondiagnostic surgery within 4 weeks of Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) | first cycle (3-week cycle) of Cohort A, Cohort B, and Cohort C |
Secondary
| Measure | Time frame |
|---|---|
| Event-free Survival According to the International Workshop to Standardize Response Criteria for NHL | Day 1, after 4 and 8 cycles of therapy (12 and 24 weeks after study entry) until disease progression/relapse, or death, whichever occurred first (overall up to approximately 2.75 years) |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Day 28 (AUC0-28) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
| Percentage of Participants With Overall Response According to the International Workshop to Standardize Response Criteria for NHL | Day 1, after 4 and 8 cycles of therapy (12 and 24 weeks after study entry) until disease progression/relapse, or death, whichever occurred first (overall up to approximately 2.75 years) |
| Maximum Plasma Concentration (Cmax) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
| Progression-free Survival According to the International Workshop to Standardize Response Criteria for NHL | Day 1, after 4 and 8 cycles of therapy (12 and 24 weeks after study entry) until disease progression/relapse, or death, whichever occurred first (overall up to approximately 2.75 years) |
| Steady State Volume of Distribution (Vss) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
| Terminal Elimination Half-Life (t1/2) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
| Number of Participants With Peripheral Blood B-cell Depletion | Week 24, 28 days following the final infusion (Day 176), 9, 18, 24, and 30 months after study entry or until B cell recovery, whichever occurred first (up to approximately 2.75 years) |
| Number of Participants With Peripheral Blood B-cell Recovery | Week 24, 28 days following the final infusion (Day 176), 9, 18, 24, and 30 months after study entry or until B cell recovery, whichever occurred first (up to approximately 2.75 years) |
| Systemic Clearance (CL) of Ocrelizumab | Pre-infusion (0-2 hours); 30 minutes post infusion on Day 1 of Cycles 1 to 8 (Cycle length = 21 days); Days 2, 8, and 15 of Cycle 1 (Cohorts A, B), Cycle 2 (Cohort C), and Cycle 8 (Cohorts A, B, C); Days 176, 190, 204, 259, 322, 357, 539 |
Countries
Australia, Canada, France, Italy, Sweden, Switzerland
Outcome results
None listed