A Study of Ocrelizumab in Participants With Follicular Non-Hodgkin's Lymphoma (NHL)
- Registration Number
- NCT02723071
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy of ocrelizumab in participants with progressive follicular NHL.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Ocrelizumab 200 mg/m^2 Ocrelizumab Participants will receive a total of 8 infusions of ocrelizumab 200 milligram per square meter (mg/m\^2) given at intervals of 3 weeks, until disease progression or unacceptable toxicity. Cohort B: Ocrelizumab 375 mg/m^2 Ocrelizumab Participants will receive a total of 8 infusions of ocrelizumab 375 mg/m\^2 given at intervals of 3 weeks, until disease progression or unacceptable toxicity. Cohort C: Ocrelizumab 375/750 mg/m^2 Ocrelizumab Participants will receive first infusion of ocrelizumab 375 mg/m\^2 followed by 7 infusions of 750 mg/m\^2 given at intervals of 3 weeks, until disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-limiting Toxicity (DLT) first cycle (3-week cycle) of Cohort A, Cohort B, and Cohort C
- Secondary Outcome Measures
Name Time Method 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 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) 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) 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 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 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 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) 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 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) 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 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