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

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

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

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3002
  • Perth, Australia, 6000
  • Woolloongabba, Australia, 4102
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1C4
    • Toronto, Ontario, Canada, M5G 2M9
• France
  • Creteil, France, 94010
  • Lille, France, 59037
  • Nantes, France, 44093
  • Pierre Benite, France, 69495
  • Rennes, France, 35033
• Italy
  • Bergamo, Italy, 24127
  • Roma, Italy, 00161
  • Torino, Italy, 10126
• Sweden
  • Huddinge, Sweden, 14186
  • Lund, Sweden, 22185
  • Malmoe, Sweden, 20502
  • Umea, Sweden, 90185
• Switzerland
  • Bern, Switzerland, 3010
  • Geneve, Switzerland, 1211
  • Lugano, Switzerland, 6900

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: March 24, 2016
• First Posted (Estimate): March 30, 2016

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 24, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: BO18414; 2004-004110-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No