Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00825149
First received: January 16, 2009
Last updated: November 3, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Bendamustine
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Fludarabine
Drug: Obinutuzumab
Drug: Prednisone
Drug: Vincristine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) - Relapsed/Refractory Population [ Time Frame: Baseline up to maximum observation time of 79.5 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With AEs - First-line Population [ Time Frame: Baseline up to maximum observation time of 59.7 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 137
Study Start Date: February 2009
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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.
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: 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.
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.
Drug: Cyclophosphamide
Cyclophosphamide 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
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.
Drug: Cyclophosphamide
Cyclophosphamide 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
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.
Drug: Bendamustine
Bendamustine 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
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.
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: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00825149

  Show 34 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00825149     History of Changes
Other Study ID Numbers: BO21000  2008-001643-19 
Study First Received: January 16, 2009
Last Updated: November 3, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Bendamustine Hydrochloride
Liposomal doxorubicin
Fludarabine
Obinutuzumab
Doxorubicin
Prednisone
Vincristine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016