A Study of Ocrelizumab in Participants With Follicular Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy of ocrelizumab in participants with progressive follicular NHL.

Official Title
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An Open-label, Multicentre, Dose-escalating Phase I/II Trial of 3-weekly Ocrelizumab in Patients With Follicular Non-Hodgkin's Lymphoma (NHL)

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Ocrelizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Ocrelizumab 200 mg/m^2<br>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. | Drug: Ocrelizumab<br>* Participants will receive a total of 8 intravenous (IV) infusions of ocrelizumab given at intervals of 3 weeks, until disease progression or unacceptable toxicity.<br>* Other names: RO4964913;|
| Experimental: Cohort B: Ocrelizumab 375 mg/m^2<br>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. | Drug: Ocrelizumab<br>* Participants will receive a total of 8 intravenous (IV) infusions of ocrelizumab given at intervals of 3 weeks, until disease progression or unacceptable toxicity.<br>* Other names: RO4964913;|
| Experimental: Cohort C: Ocrelizumab 375/750 mg/m^2<br>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. | Drug: Ocrelizumab<br>* Participants will receive a total of 8 intravenous (IV) infusions of ocrelizumab given at intervals of 3 weeks, until disease progression or unacceptable toxicity.<br>* Other names: RO4964913;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-limiting Toxicity (DLT) |  | first cycle (3-week cycle) of Cohort A, Cohort B, and Cohort C | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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 | 
| 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) |