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

Roche

Status and phase: Completed; Phase 1

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Bendamustine; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Fludarabine; Drug: Prednisone; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00825149

BO21000

2008-001643-19

Details and patient eligibility

About

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.

Enrollment: 137 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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137 participants in 6 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Prednisone

Drug: Vincristine

Drug: Doxorubicin

Drug: Cyclophosphamide

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

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Prednisone

Drug: Vincristine

Drug: Doxorubicin

Drug: Cyclophosphamide

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

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Fludarabine

Drug: Cyclophosphamide

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

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Fludarabine

Drug: Cyclophosphamide

E: First-Line FL: Obinutuzumab + Bendamustine

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Bendamustine

F: First-Line FL: Obinutuzumab + CHOP

Experimental group

Description:

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.

Treatment:

Drug: Obinutuzumab

Drug: Prednisone

Drug: Vincristine

Drug: Doxorubicin

Drug: Cyclophosphamide