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A Study of Obinutuzumab in Combination With Chemotherapy in Participants With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma (GAUDI)

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ClinicalTrials.gov Identifier: NCT00825149
Recruitment Status : Completed
First Posted : January 19, 2009
Last Update Posted : November 4, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 16, 2009
First Posted Date  ICMJE January 19, 2009
Last Update Posted Date November 4, 2016
Study Start Date  ICMJE February 2009
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 16, 2009)
Adverse events, infusion-related reactions, laboratory parameters [ Time Frame: Up to 12 months ]
Change History Complete list of historical versions of study NCT00825149 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2016)
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2009)
  • End of treatment response [ Time Frame: Week 24 ]
  • Best overall response [ Time Frame: Event driven;up to 12 months ]
  • Duration of response [ Time Frame: Event driven;up to 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Obinutuzumab in Combination With Chemotherapy in Participants With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • Drug: Bendamustine
    Bendamustine will be administered as per schedule specified in the respective arm.
  • Drug: Cyclophosphamide
    Cyclophosphamide will be administered as per schedule specified in the respective arm.
  • Drug: Doxorubicin
    Doxorubicin will be administered as per schedule specified in the respective arm.
  • Drug: Fludarabine
    Fludarabine will be administered as per schedule specified in the respective arm.
  • Drug: Obinutuzumab
    Obinutuzumab will be administered as per schedule specified in the respective arm.
    Other Name: RO5072759
  • Drug: Prednisone
    Prednisone will be administered as per schedule specified in the respective arm.
  • Drug: Vincristine
    Vincristine will be administered as per schedule specified in the respective arm.
Study Arms  ICMJE
  • Experimental: A: R/R FL: Obinutuzumab Low Dose + CHOP
    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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Prednisone
    • Drug: Vincristine
  • Experimental: B: R/R FL: Obinutuzumab High Dose + CHOP
    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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Prednisone
    • Drug: Vincristine
  • Experimental: C: R/R FL: Obinutuzumab Low Dose + FC
    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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Drug: Obinutuzumab
  • Experimental: D: R/R FL: Obinutuzumab High Dose + FC
    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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Drug: Obinutuzumab
  • Experimental: E: First-Line FL: Obinutuzumab + Bendamustine
    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.
    Interventions:
    • Drug: Bendamustine
    • Drug: Obinutuzumab
  • Experimental: F: First-Line FL: Obinutuzumab + CHOP
    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.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Prednisone
    • Drug: Vincristine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 24, 2014)
137
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2009)
56
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00825149
Other Study ID Numbers  ICMJE BO21000
2008-001643-19
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP