Clinical trial NCT00825149: A Study of Obinutuzumab in Combination With Chemotherapy in Participants With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma
Official title: An Open-Label, Multi-Centre, Randomised, Phase Ib Study to Investigate the Safety and Efficacy of RO5072759 Given in Combination With CHOP, FC or Bendamustine Chemotherapy in Patients With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-01-19
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Either CD20+ R/R B-cell follicular non-Hodgkin's lymphoma (after a maximum of 2 prior chemotherapy regimens) or CD20+ B-cell follicular non-Hodgkin's lymphoma with no prior systemic therapy
* Must have at least one bi-dimensionally measurable lesion (greater than \[\>\] 1.5 centimeters \[cm\] in its largest dimension by computed tomography \[CT\] scan)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

* For R/R participants recruited in Obinutuzumab + CHOP regimen, prior use of anthracyclines. For R/R participants recruited in Obinutuzumab + FC regimen, immediate prior treatment should not have contained fludarabine or fluoropyrimidines. For first-line recruited participants, prior systemic therapy
* Prior administration of rituximab within 56 days of study entry, or 3 months for any radioimmunotherapy
* Central nervous system lymphoma
* History of other malignancies within 2 years of study entry which could affect compliance with the protocol or interpretation of results
* Known active bacterial, viral (including human immunodeficiency virus \[HIV\]), fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
* Contraindication to any of the individual components of chemotherapy (as per local prescribing information), of the selected chemotherapy combination (FC, CHOP or bendamustine)

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) - Relapsed/Refractory Population
timeFrame: Baseline up to maximum observation time of 79.5 months
measure: Percentage of Participants With AEs - First-line Population
timeFrame: Baseline up to maximum observation time of 59.7 months
Secondary outcomes:
measure: Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
timeFrame: 28 days after end of induction treatment (up to 28 weeks)
measure: Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
timeFrame: 28 days after end of induction treatment (up to 28 weeks)
measure: Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
timeFrame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)
measure: Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
timeFrame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)
measure: Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
timeFrame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)
measure: Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
timeFrame: Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)
measure: 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
timeFrame: Baseline up to disease progression or death (up to maximum observation time of 79.5 months)
measure: 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
timeFrame: Baseline up to disease progression or death (up to maximum observation time of 59.7 months)
measure: PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
timeFrame: Baseline up to disease progression or death (up to maximum observation time of 79.5 months)
measure: PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
timeFrame: Baseline up to disease progression or death (up to maximum observation time of 59.7 months)
measure: 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
timeFrame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
measure: 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
timeFrame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 59.7 months)
measure: EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population
timeFrame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
measure: EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population
timeFrame: Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)
measure: Pharmacokinetics of Obinutuzumab: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: AUClast - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Maximum Observed Plasma Concentration (Cmax) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Cmax - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Systemic Clearance at Steady State (CLss) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: CLss - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: AUC From Time Zero to 7 Days (AUC7d) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: AUC7d - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Volume of Distribution at Steady State (Vss) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Vss - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Plasma Half-life (t1/2) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: t1/2 - First-line Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Plasma Trough Concentration (Ctrough) - Relapsed/Refractory Population
timeFrame: 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)
measure: Pharmacokinetics of Obinutuzumab: Ctrough - First-line Population
timeFrame: 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)
measure: Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - Relapsed/Refractory Population
timeFrame: Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 79.5 months)
measure: Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - First-line Population
timeFrame: Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 59.7 months)
measure: Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - Relapsed/Refractory Population
timeFrame: From end of treatment to B-cell recovery (up to the maximum observation time of 79.5 months)
measure: Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - First-line Population
timeFrame: From end of treatment to B-cell recovery (up to the maximum observation time of 59.7 months)
Other outcomes:
Locations:
city: Kogarah
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Greenslopes
country: Australia
state: Queensland
city: Woolloongabba
country: Australia
state: Queensland
city: Kurralta Park
country: Australia
state: South Australia
city: Frankston
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Lille
country: France
city: Montpellier
country: France
city: Pierre Benite
country: France
city: Aschaffenburg
country: Germany
city: Freiburg
country: Germany
city: Göttingen
country: Germany
city: Heidelberg
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Muenchen
country: Germany
city: Ulm
country: Germany
city: Würzburg
country: Germany
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Southampton
country: United Kingdom
city: Truro
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
citation: Grigg A, Dyer MJ, Diaz MG, Dreyling M, Rule S, Lei G, Knapp A, Wassner-Fritsch E, Marlton P. Safety and efficacy of obinutuzumab with CHOP or bendamustine in previously untreated follicular lymphoma. Haematologica. 2017 Apr;102(4):765-772. doi: 10.3324/haematol.2016.152272. Epub 2016 Dec 23.
citation: Cartron G, Hourcade-Potelleret F, Morschhauser F, Salles G, Wenger M, Truppel-Hartmann A, Carlile DJ. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Haematologica. 2016 Feb;101(2):226-34. doi: 10.3324/haematol.2015.133421. Epub 2015 Dec 11.
citation: Radford J, Davies A, Cartron G, Morschhauser F, Salles G, Marcus R, Wenger M, Lei G, Wassner-Fritsch E, Vitolo U. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood. 2013 Aug 15;122(7):1137-43. doi: 10.1182/blood-2013-01-481341. Epub 2013 Jul 10.