This open-label, randomized, phase Ib study will assess the safety and efficacy of obinutuzumab given in combination with FC (fludarabine and cyclophosphamide) or CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) or bendamustine induction chemotherapy in participants with Cluster of Differentiation (CD) 20+ B-cell Follicular Lymphoma (FL). Participants with complete response or partial response after induction therapy may receive maintenance therapy every 3 months for 2 years or until disease progression, whichever comes first. All participants in the induction period of the study will have a safety follow-up visit 28 days after completing the last dose of obinutuzumab + chemotherapy, and will be followed for at least 2 years, unless they are being treated in maintenance or discontinue from the study prior to this time point. Participants who complete/discontinue maintenance therapy will also be followed for a period of 2 years after receiving the last dose of obinutuzumab or until progression/new antilymphoma treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
137
Bendamustine will be administered as per schedule specified in the respective arm.
Cyclophosphamide will be administered as per schedule specified in the respective arm.
Doxorubicin will be administered as per schedule specified in the respective arm.
Fludarabine will be administered as per schedule specified in the respective arm.
Obinutuzumab will be administered as per schedule specified in the respective arm.
Prednisone will be administered as per schedule specified in the respective arm.
Vincristine will be administered as per schedule specified in the respective arm.
Unnamed facility
Kogarah, New South Wales, Australia
Unnamed facility
Sydney, New South Wales, Australia
Unnamed facility
Greenslopes, Queensland, Australia
Unnamed facility
Woolloongabba, Queensland, Australia
Unnamed facility
Kurralta Park, South Australia, Australia
Unnamed facility
Frankston, Victoria, Australia
Unnamed facility
Melbourne, Victoria, Australia
Unnamed facility
Melbourne, Victoria, Australia
Unnamed facility
Lille, France
Unnamed facility
Montpellier, France
...and 24 more locations
Percentage of Participants With Adverse Events (AEs) - Relapsed/Refractory Population
Time frame: Baseline up to maximum observation time of 79.5 months
Percentage of Participants With AEs - First-line Population
Time frame: Baseline up to maximum observation time of 59.7 months
Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: 28 days after end of induction treatment (up to 28 weeks)
Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: 28 days after end of induction treatment (up to 28 weeks)
Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)
Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)
Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)
Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)
Number of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Relapse or Death), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to disease progression or death (up to maximum observation time of 79.5 months)
Number of Participants With PFS Events (Disease Progression/Relapse or Death), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: Baseline up to disease progression or death (up to maximum observation time of 59.7 months)
PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to disease progression or death (up to maximum observation time of 79.5 months)
PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: Baseline up to disease progression or death (up to maximum observation time of 59.7 months)
Number of Participants With Event-Free Survival (EFS) Event (Disease Progression, Death, or Initiation of a New Anti-Lymphoma Therapy), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
Number of Participants With EFS Event (Disease Progression, Death, or Initiation of a New Anti-Lymphoma Therapy), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 59.7 months)
EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
Time frame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
Time frame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
Pharmacokinetics of Obinutuzumab: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hour {hr}], end of infusion [EOI, approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: AUClast - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Maximum Observed Plasma Concentration (Cmax) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Cmax - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Systemic Clearance at Steady State (CLss) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: CLss - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: AUC From Time Zero to 7 Days (AUC7d) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: AUC7d - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Volume of Distribution at Steady State (Vss) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Vss - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Plasma Half-life (t1/2) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: t1/2 - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Plasma Trough Concentration (Ctrough) - Relapsed/Refractory Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacokinetics of Obinutuzumab: Ctrough - First-line Population
Time frame: Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)
Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - Relapsed/Refractory Population
Time frame: Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 79.5 months)
Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - First-line Population
Time frame: Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 59.7 months)
Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - Relapsed/Refractory Population
Time frame: From end of treatment to B-cell recovery (up to the maximum observation time of 79.5 months)
Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - First-line Population
Time frame: From end of treatment to B-cell recovery (up to the maximum observation time of 59.7 months)
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