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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT00825149

Collaborator

(none)

137

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

137 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]
Percentage of Participants With Best Overall Response of Complete 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)]
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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [From end of treatment to B-cell recovery (up to the maximum observation time of 59.7 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	City	State	Country	Postal Code
1	Kogarah	New South Wales	Australia	2217
2	Sydney	New South Wales	Australia	2145
3	Greenslopes	Queensland	Australia	4120
4	Woolloongabba	Queensland	Australia	4102
5	Kurralta Park	South Australia	Australia	5037
6	Frankston	Victoria	Australia	3199
7	Melbourne	Victoria	Australia	3000
8	Melbourne	Victoria	Australia	3084
9	Lille		France	59037
10	Montpellier		France	34295
11	Pierre Benite		France	69495
12	Aschaffenburg		Germany	63739
13	Freiburg		Germany	79106
14	Göttingen		Germany	37075
15	Heidelberg		Germany	69120
16	Kiel		Germany	24105
17	Köln		Germany	50924
18	Muenchen		Germany	81377
19	Ulm		Germany	89081
20	Würzburg		Germany	97080
21	Roma	Lazio	Italy	00161
22	Milano	Lombardia	Italy	20132
23	Torino	Piemonte	Italy	10126
24	Barcelona		Spain	08003
25	Barcelona		Spain	08035
26	Barcelona		Spain	08036
27	Salamanca		Spain	37007
28	Valencia		Spain	46026
29	Leicester		United Kingdom	LE1 5WW
30	London		United Kingdom	SE5 9RS
31	Manchester		United Kingdom	M20 4QL
32	Plymouth		United Kingdom	PL6 8DH
33	Southampton		United Kingdom	SO16 6YD
34	Truro		United Kingdom	TR1 3LJ