A Dose-Escalating Study of Obinutuzumab in Patients With B-lymphocyte Antigen (CD20+) Malignant Disease (GAUGUIN)

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphoma

Treatments: Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00517530

2007-001103-37 (EudraCT Number)

BO20999

Details and patient eligibility

About

The primary objective for the phase I part of the study is to investigate the safety and tolerability of escalating intravenous (IV) doses of obinutuzumab given as monotherapy in participants with CD20+ (tumor-infiltrating lymphocytic) Malignant Disease, including B-cell chronic lymphocytic leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). The primary objective for the phase II part of the study is to investigate the efficacy and safety of one dose of obinutuzumab in participants with relapsed/refractory CLL and NHL that is, in turn, either indolent (iNHL) or aggressive (aNHL).

It is an open label dose escalating study in phase I and open label in phase II, but the two doses in iNHL & aNHL are randomized (to high or low dose of the same open label treatment). CLL was not randomized as only one dose level was used.

Participants with a response who might gain additional benefit from being treated again in the opinion of the investigator may be enrolled in a Retreatment Period.

Enrollment: 134 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients, >=18 years of age;
• Phase 1 only: CD20+ malignant disease (B-cell lymphoma or B-CLL);
• Phase 2 only: relapsed or refractory indolent NHL, relapsed or refractory aggressive NHL or relapsed or refractory B-CLL
• Have a clinical indication for treatment as determined by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Life expectancy >12 weeks

Exclusion criteria

• Prior use of any investigational antibody therapy or other agent within 6 months of study start;
• Prior use of any anti-cancer vaccine;
• Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment;
• Prior use of MabThera (rituximab) within 8 weeks of study entry;
• Prior administration of radioimmunotherapy 3 months prior to study entry;
• Central nervous system (CNS) lymphoma.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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134 participants in 8 patient groups

Phase I, NHL

Experimental group

Description:

Participants in this NHL arm received multiple ascending doses between 50 and 2000 mg via intravenous infusion of obinutuzumab.

Treatment:

Drug: Obinutuzumab

Phase I, CLL

Experimental group

Description:

Participants in this CLL arm received multiple ascending doses between 400 and 2000 mg via intravenous infusion of obinutuzumab.

Treatment:

Drug: Obinutuzumab

400/400 mg - Phase II, iNHL

Experimental group

Description:

Participants in this iNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.

Treatment:

Drug: Obinutuzumab

1600/800 mg - Phase II, iNHL

Experimental group

Description:

Participants in this iNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.

Treatment:

Drug: Obinutuzumab

400/400 mg - Phase II, aNHL

Experimental group

Description:

Participants in this aNHL arm received an intravenous infusion of obinutuzumab 400 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 400 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.

Treatment:

Drug: Obinutuzumab

1600/800 mg - Phase II, aNHL

Experimental group

Description:

Participants in this aNHL arm received an intravenous infusion of obinutuzumab 1600 mg on Days 1 and 8 of Cycle 1 and obinutuzumab 800 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 9 infusions. Each cycle was 21 days.

Treatment:

Drug: Obinutuzumab

1000/1000 mg - Phase II, CLL

Experimental group

Description:

Participants in this CLL arm received an intravenous infusion of obinutuzumab 1000 mg on Days 1, 8, and 15 of Cycle 1 and obinutuzumab 1000 mg on Day 1 of Cycles 2-8 for a maximum of 8 cycles and 10 infusions. Each cycle was 21 days.

Treatment:

Drug: Obinutuzumab

Retreated Participants

Experimental group

Description:

Participants who might benefit from retreatment who were allowed to be treated again via intravenous infusion of obinutuzumab at the request of the investigator.

Treatment:

Drug: Obinutuzumab