Clinical trial NCT00576758: GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma
Official title: An Open-label, Multi-center, Randomized Study to Evaluate the Efficacy on Tumor Response of GA101 (RO5072759) Monotherapy Versus Rituximab Monotherapy in Patients With Relapsed CD20+ Indolent Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-12-19
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will investigate the efficacy of weekly intravenous obinutuzumab \[GA101 (RO5072759)\] monotherapy, in patients with relapsed CD20+ indolent Non-Hodgkin's Lymphoma. Patients will be randomized to receive either GA101 or rituximab, given as four weekly infusions. At the conclusion of the initial trial patients may be eligible to continue therapy up to 24 months. The anticipated time on study treatment is 3- 24 months, and the target sample size is 100-500 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>=18 years of age
* relapsed CD20+ indolent B-cell non-Hodgkin's lymphoma
* documented history of response of \>/= 6 months duration from last rituximab-containing regimen
* clinical indication for treatment as determined by the investigator
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

* prior use of any investigational monoclonal antibody within 6 months of study start
* prior use of any anti-cancer vaccine
* prior use of rituximab within 8 weeks of study entry
* radioimmunotherapy within 3 months prior to study entry
* Central Nervous System (CNS) lymphoma or evidence of transformation to high-grade or diffuse large B-cell lymphoma

Primary outcomes:
measure: Percentage of Participants With Overall Response At the End of Induction Period
timeFrame: Randomization to clinical cutoff: 01 September 2011 (Up to 70 days)
Secondary outcomes:
measure: Percentage of Participants With Complete Response at the End of the Induction Period
timeFrame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)
measure: Percentage of Participants With Partial Response (PR) at the End of the Induction Period
timeFrame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)
measure: Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment
timeFrame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days)
measure: Number of Participants With Improved Overall Response During the Extended Treatment Period
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Progression-Free Survival (PFS)
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Percentage of Participants With Progression-Free Survival (PFS) Events
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Event Free Survival
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Percentage of Participants With Event Free Survival (EFS) Events
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Duration of Response
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2)
timeFrame: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax)
timeFrame: Day 1 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours post-infusion), Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast)
timeFrame: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss)
timeFrame: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau)
timeFrame: Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Obinutuzumab Trough Serum Concentration (Ctrough)
timeFrame: Days 8 and 15 (pre-infusion, at end of infusion), Day 22 (pre-infusion, at end of infusion, 3-6, 20-28, 66-80 hours, 6-8, 12-16, 18-24, 28-56 days post-infusion)
measure: Number of Participants With Peripheral Blood B-Cell Depletion
timeFrame: Day 22
measure: Number of Participants With Peripheral Blood B-Cell Recovery
timeFrame: End of last dose + 6 Months Follow-Up
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) [Includes all AEs reported 28 days after last dose and all Related SAEs regardless of time of last dose.]
measure: Number of Participants With Infusion Related Reactions
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
measure: Number of Participants With Human Anti-Chimeric Antibodies (HACA)
timeFrame: Day 1
measure: Number of Participants With Human Anti-Human Antibodies (HAHA)
timeFrame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months)
Other outcomes:
Locations:
city: Los angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Gainesville
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Cumberland
country: United States
state: Maryland
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Concord
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Mont-godinne
country: Belgium
city: Goiania
country: Brazil
state: GO
city: Porto Alegre
country: Brazil
state: RS
city: Piracicaba
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Kingston
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Rijeka
country: Croatia
city: Zagreb
country: Croatia
city: København
country: Denmark
city: Vejle
country: Denmark
city: Århus
country: Denmark
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Novara
country: Italy
city: Pisa
country: Italy
city: Reggio Calabria
country: Italy
city: Rozzano
country: Italy
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Palma de Mallorca
country: Spain
state: Islas Baleares
city: La Coruna
country: Spain
state: La Coruña
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Huddinge
country: Sweden
city: Malmo
country: Sweden
city: St. Gallen
country: Switzerland
city: Zürich
country: Switzerland
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: London
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
citation: Kostakoglu L, Goy A, Martinelli G, Caballero D, Crump M, Gaidano G, Baetz T, Buckstein R, Fine G, Fingerle-Rowson G, Berge C, Sahin D, Press O, Sehn L. FDG-PET is prognostic and predictive for progression-free survival in relapsed follicular lymphoma: exploratory analysis of the GAUSS study. Leuk Lymphoma. 2017 Feb;58(2):372-381. doi: 10.1080/10428194.2016.1196815. Epub 2016 Jun 24.
citation: Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. doi: 10.1200/JCO.2014.59.2139. Epub 2015 Aug 17.
citation: Sehn LH, Assouline SE, Stewart DA, Mangel J, Gascoyne RD, Fine G, Frances-Lasserre S, Carlile DJ, Crump M. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood. 2012 May 31;119(22):5118-25. doi: 10.1182/blood-2012-02-408773. Epub 2012 Mar 20.