Clinical trial NCT02723071: A Study of Ocrelizumab in Participants With Follicular Non-Hodgkin's Lymphoma (NHL)
Official title: An Open-label, Multicentre, Dose-escalating Phase I/II Trial of 3-weekly Ocrelizumab in Patients With Follicular Non-Hodgkin's Lymphoma (NHL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-03-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicity (DLT)
timeFrame: first cycle (3-week cycle) of Cohort A, Cohort B, and Cohort C
Secondary outcomes:
measure: Progression-free Survival According to the International Workshop to Standardize Response Criteria for NHL
timeFrame: 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)
measure: Event-free Survival According to the International Workshop to Standardize Response Criteria for NHL
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Day 28 (AUC0-28) of Ocrelizumab
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity AUC(0-inf) of Ocrelizumab
timeFrame: 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
measure: Percentage of Participants With Overall Response According to the International Workshop to Standardize Response Criteria for NHL
timeFrame: 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)
measure: Maximum Plasma Concentration (Cmax) of Ocrelizumab
timeFrame: 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
measure: Systemic Clearance (CL) of Ocrelizumab
timeFrame: 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
measure: Steady State Volume of Distribution (Vss) of Ocrelizumab
timeFrame: 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
measure: Terminal Elimination Half-Life (t1/2) of Ocrelizumab
timeFrame: 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
measure: Number of Participants With Peripheral Blood B-cell Depletion
timeFrame: 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)
measure: Number of Participants With Peripheral Blood B-cell Recovery
timeFrame: 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)
Other outcomes:
Locations:
city: Melbourne
country: Australia
city: Perth
country: Australia
city: Woolloongabba
country: Australia
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Creteil
country: France
city: Lille
country: France
city: Nantes
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Bergamo
country: Italy
city: Roma
country: Italy
city: Torino
country: Italy
city: Huddinge
country: Sweden
city: Lund
country: Sweden
city: Malmoe
country: Sweden
city: Umea
country: Sweden
city: Bern
country: Switzerland
city: Geneve
country: Switzerland
city: Lugano
country: Switzerland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: