NCT00825149

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
137

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2009

Longer than P75 for phase_1

Geographic Reach
6 countries

34 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 16, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 19, 2009

Completed
13 days until next milestone

Study Start

First participant enrolled

February 1, 2009

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
Last Updated

November 4, 2016

Status Verified

November 1, 2016

Enrollment Period

6.8 years

First QC Date

January 16, 2009

Last Update Submit

November 3, 2016

Conditions

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants With Adverse Events (AEs) - Relapsed/Refractory Population

    Baseline up to maximum observation time of 79.5 months

  • Percentage of Participants With AEs - First-line Population

    Baseline up to maximum observation time of 59.7 months

Secondary Outcomes (32)

  • Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population

    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

    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

    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

    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

    Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)

  • +27 more secondary outcomes

Study Arms (6)

A: R/R FL: Obinutuzumab Low Dose + CHOP

EXPERIMENTAL

Participants with Relapsed/Refractory (R/R) FL will receive obinutuzumab 400 milligrams (mg) intravenous (IV) infusion on Days 1 and 8 of Cycle 1 and every 3 weeks on Day 1 of subsequent cycles (for 68 cycles) in the induction period; Prednisone 100 mg/day orally on Days 15, doxorubicin 50 milligrams per square-meter (mg/m\^2), vincristine 1.4 mg/m\^2 capped at 2 mg, and cyclophosphamide 750 mg/m\^2 IV infusion every 3 weeks on Day 1 of each cycle for 68 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 400 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: CyclophosphamideDrug: DoxorubicinDrug: ObinutuzumabDrug: PrednisoneDrug: Vincristine

B: R/R FL: Obinutuzumab High Dose + CHOP

EXPERIMENTAL

Participants with R/R FL will receive obinutuzumab 1600 mg IV infusion on Days 1 and 8 of Cycle 1 and 800 mg IV infusion every 3 weeks on Day 1 of subsequent cycles (for 68 cycles) in the induction period; Prednisone 100 mg/day orally on Days 15, doxorubicin 50 mg/m\^2, vincristine 1.4 mg/m\^2 capped at 2 mg, and cyclophosphamide 750 mg/m\^2 IV infusion every 3 weeks on Day 1 of each cycle for 68 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 800 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: CyclophosphamideDrug: DoxorubicinDrug: ObinutuzumabDrug: PrednisoneDrug: Vincristine

C: R/R FL: Obinutuzumab Low Dose + FC

EXPERIMENTAL

Participants with R/R FL will receive obinutuzumab 400 mg IV infusion on Days 1 and 8 of Cycle 1 and every 4 weeks on Day 1 of subsequent cycles (for 46 cycles) in the induction period; Fludarabine 25 mg/m\^2/day and cyclophosphamide 250 mg/m\^2/day IV infusion every 4 weeks on Days 13 of each cycle for 46 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 400 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: CyclophosphamideDrug: FludarabineDrug: Obinutuzumab

D: R/R FL: Obinutuzumab High Dose + FC

EXPERIMENTAL

Participants with R/R FL will receive obinutuzumab 1600 mg IV infusion on Days 1 and 8 of Cycle 1 and 800 mg IV infusion every 4 weeks on Days 1 of subsequent cycles (for 46 cycles) in the induction period; Fludarabine 25 mg/m\^2/day and cyclophosphamide 250 mg/m\^2/day IV infusion every 4 weeks on Days 13 of each cycle for 46 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 800 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: CyclophosphamideDrug: FludarabineDrug: Obinutuzumab

E: First-Line FL: Obinutuzumab + Bendamustine

EXPERIMENTAL

Participants with first-line FL will receive obinutuzumab 1000 mg IV infusion on Days 1 and 8 of Cycle 1 and every 4 weeks on Day 1 of subsequent cycles (for 46 cycles) in the induction period; Bendamustine 90 mg/m\^2 IV infusion on Days 2 and 3 of Cycle 1 and every 4 weeks on Days 1 and 2 of each subsequent cycle for 46 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 1000 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: BendamustineDrug: Obinutuzumab

F: First-Line FL: Obinutuzumab + CHOP

EXPERIMENTAL

Participants with first-line FL will receive obinutuzumab 1000 mg IV infusion on Days 1 and 8 of Cycle 1 and every 3 weeks on Day 1 of subsequent cycles (for 68 cycles) in the induction period; Prednisone 100 mg/day orally on Days 15, doxorubicin 50 mg/m\^2, vincristine 1.4 mg/m\^2 capped at 2 mg, cyclophosphamide 750 mg/m\^2 IV infusion every 3 weeks on Day 1 of each cycle for 68 cycles in the induction period. 12 weeks following last infusion, participants with CR or PR will be eligible to receive 1000 mg obinutuzumab IV infusion once every 3 months for 2 years or until disease progression in the maintenance period.

Drug: CyclophosphamideDrug: DoxorubicinDrug: ObinutuzumabDrug: PrednisoneDrug: Vincristine

Interventions

Bendamustine will be administered as per schedule specified in the respective arm.

E: First-Line FL: Obinutuzumab + Bendamustine

Cyclophosphamide will be administered as per schedule specified in the respective arm.

A: R/R FL: Obinutuzumab Low Dose + CHOPB: R/R FL: Obinutuzumab High Dose + CHOPC: R/R FL: Obinutuzumab Low Dose + FCD: R/R FL: Obinutuzumab High Dose + FCF: First-Line FL: Obinutuzumab + CHOP

Doxorubicin will be administered as per schedule specified in the respective arm.

A: R/R FL: Obinutuzumab Low Dose + CHOPB: R/R FL: Obinutuzumab High Dose + CHOPF: First-Line FL: Obinutuzumab + CHOP

Fludarabine will be administered as per schedule specified in the respective arm.

C: R/R FL: Obinutuzumab Low Dose + FCD: R/R FL: Obinutuzumab High Dose + FC

Obinutuzumab will be administered as per schedule specified in the respective arm.

Also known as: RO5072759
A: R/R FL: Obinutuzumab Low Dose + CHOPB: R/R FL: Obinutuzumab High Dose + CHOPC: R/R FL: Obinutuzumab Low Dose + FCD: R/R FL: Obinutuzumab High Dose + FCE: First-Line FL: Obinutuzumab + BendamustineF: First-Line FL: Obinutuzumab + CHOP

Prednisone will be administered as per schedule specified in the respective arm.

A: R/R FL: Obinutuzumab Low Dose + CHOPB: R/R FL: Obinutuzumab High Dose + CHOPF: First-Line FL: Obinutuzumab + CHOP

Vincristine will be administered as per schedule specified in the respective arm.

A: R/R FL: Obinutuzumab Low Dose + CHOPB: R/R FL: Obinutuzumab High Dose + CHOPF: First-Line FL: Obinutuzumab + CHOP

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (34)

Unknown Facility

Kogarah, New South Wales, 2217, Australia

Location

Unknown Facility

Sydney, New South Wales, 2145, Australia

Location

Unknown Facility

Greenslopes, Queensland, 4120, Australia

Location

Unknown Facility

Woolloongabba, Queensland, 4102, Australia

Location

Unknown Facility

Kurralta Park, South Australia, 5037, Australia

Location

Unknown Facility

Frankston, Victoria, 3199, Australia

Location

Unknown Facility

Melbourne, Victoria, 3000, Australia

Location

Unknown Facility

Melbourne, Victoria, 3084, Australia

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Montpellier, 34295, France

Location

Unknown Facility

Pierre-Bénite, 69495, France

Location

Unknown Facility

Aschaffenburg, 63739, Germany

Location

Unknown Facility

Cologne, 50924, Germany

Location

Unknown Facility

Freiburg im Breisgau, 79106, Germany

Location

Unknown Facility

Göttingen, 37075, Germany

Location

Unknown Facility

Heidelberg, 69120, Germany

Location

Unknown Facility

Kiel, 24105, Germany

Location

Unknown Facility

München, 81377, Germany

Location

Unknown Facility

Ulm, 89081, Germany

Location

Unknown Facility

Würzburg, 97080, Germany

Location

Unknown Facility

Rome, Lazio, 00161, Italy

Location

Unknown Facility

Milan, Lombardy, 20132, Italy

Location

Unknown Facility

Turin, Piedmont, 10126, Italy

Location

Unknown Facility

Barcelona, Barcelona, 08003, Spain

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Unknown Facility

Barcelona, Barcelona, 08035, Spain

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Unknown Facility

Barcelona, Barcelona, 08036, Spain

Location

Unknown Facility

Salamanca, Salamanca, 37007, Spain

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Unknown Facility

Valencia, Valencia, 46026, Spain

Location

Unknown Facility

Leicester, LE1 5WW, United Kingdom

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Unknown Facility

London, SE5 9RS, United Kingdom

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Unknown Facility

Manchester, M20 4QL, United Kingdom

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Unknown Facility

Plymouth, PL6 8DH, United Kingdom

Location

Unknown Facility

Southampton, SO16 6YD, United Kingdom

Location

Unknown Facility

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (4)

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Bendamustine HydrochlorideCyclophosphamideDoxorubicinfludarabineobinutuzumabPrednisoneVincristine

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

ButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPhosphoramide MustardsPhosphoramidesOrganophosphorus CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesIndolizidinesIndolizines

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 16, 2009

First Posted

January 19, 2009

Study Start

February 1, 2009

Primary Completion

November 1, 2015

Study Completion

November 1, 2015

Last Updated

November 4, 2016

Record last verified: 2016-11

Locations