GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00576758
First received: December 18, 2007
Last updated: August 15, 2014
Last verified: August 2014
Results First Received: November 27, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non-Hodgkin's Lymphoma
Interventions: Drug: obinutuzumab (RO5072759)
Drug: rituximab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Rituximab Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.

Participant Flow for 3 periods

Period 1:   Induction Treatment Period
    Rituximab     Obinutuzumab  
STARTED     87     88  
Received Treatment     86     87  
COMPLETED     79     83  
NOT COMPLETED     8     5  
Adverse event or Intercurrent illness                 3                 3  
Insufficient therapeutic response                 2                 0  
Violation of selection criteria at entry                 1                 1  
Death                 1                 0  
Refused treatment/ Did not Cooperate                 0                 1  
Withdrew consent                 1                 0  

Period 2:   Extension Treatment Period
    Rituximab     Obinutuzumab  
STARTED     72 [1]   73 [2]
COMPLETED     30 [3]   30  
NOT COMPLETED     42     43  
Adverse event or Intercurrent illness                 6                 7  
Death                 1                 1  
Refused treatment/did not cooperate                 2                 1  
Insufficient therapeutic response                 30                 33  
Administrative/Other                 3                 1  
[1] 6 patients did not enter extended treatment phase/follow-up + 1 patient entered follow-up.
[2] 8 patients did not enter extended treatment phase/follow-up phase + 2 patients entered follow-up.
[3] + 2 patients (pts) who withdrew prior to receiving study drug.

Period 3:   Follow-up Period
    Rituximab     Obinutuzumab  
STARTED     55 [1]   51 [2]
COMPLETED     28     34  
NOT COMPLETED     27     17  
Administrative/Other                 6                 8  
Death                 3                 3  
Insufficient therapeutic response                 16                 5  
Withdrew consent                 2                 1  
[1] Includes 23 pts who entered follow-up after induction and didn't enter the extended treatment phase.
[2] Includes 21 pts who entered follow-up after induction and didn't enter the extended treatment phase.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rituximab Participants received 375 mg/m^2 rituximab IV infusion once a week on Days 1, 8, 15 and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression were eligible to receive a 375 mg/m^2 rituximab IV infusion once every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Obinutuzumab Participants received 1000 mg obinutuzumab intravenous (IV) infusion once a week on Days 1, 8, 15, and 22 in the Induction Period. 2 months following the last infusion, participants without disease progression, were eligible to receive a 1000 mg IV infusion every two months for 2 years in the Extension Period. All participants received oral acetaminophen/ paracetamol (1000 mg) and an antihistamine such as diphenhydramine (50-100 mg), 30-60 minutes prior to each infusion.
Total Total of all reporting groups

Baseline Measures
    Rituximab     Obinutuzumab     Total  
Number of Participants  
[units: participants]
  87     88     175  
Age, Customized  
[units: participants]
     
<65 years     49     47     96  
65-70 years     22     22     44  
>70 years     16     19     35  
Gender  
[units: participants]
     
Female     43     42     85  
Male     44     46     90  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Overall Response At the End of Induction Period   [ Time Frame: Randomization to clinical cutoff: 01 September 2011 (Up to 70 days) ]

2.  Secondary:   Percentage of Participants With Complete Response at the End of the Induction Period   [ Time Frame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days) ]

3.  Secondary:   Percentage of Participants With Partial Response (PR) at the End of the Induction Period   [ Time Frame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days) ]

4.  Secondary:   Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment   [ Time Frame: Randomization to clinical cutoff : 01 September 2011 (Up to 70 days) ]

5.  Secondary:   Number of Participants With Improved Overall Response During the Extended Treatment Period   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

6.  Secondary:   Percentage of Participants With Best Overall Response Achieved at Any Time During the Study Treatment   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

7.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

8.  Secondary:   Percentage of Participants With Progression-Free Survival (PFS) Events   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

9.  Secondary:   Event Free Survival   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

10.  Secondary:   Percentage of Participants With Event Free Survival (EFS) Events   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

11.  Secondary:   Duration of Response   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

12.  Secondary:   Obinutuzumab Serum PK Parameter: Terminal Half-Life (t1/2)   [ Time Frame: 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) ]

13.  Secondary:   Obinutuzumab Serum PK Parameter: Maximum Serum Concentration (Cmax)   [ Time Frame: 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) ]

14.  Secondary:   Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve (AUClast)   [ Time Frame: 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) ]

15.  Secondary:   Obinutuzumab Serum PK Parameter: Clearance at Steady-State (CLss)   [ Time Frame: 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) ]

16.  Secondary:   Obinutuzumab Serum PK Parameter: Volume of Distribution at Steady-State (Vss)   [ Time Frame: 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) ]

17.  Secondary:   Obinutuzumab Serum PK Parameter: Area Under the Concentration Curve Between Dosing Interval (AUCtau)   [ Time Frame: 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) ]

18.  Secondary:   Obinutuzumab Trough Serum Concentration (Ctrough)   [ Time Frame: 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) ]

19.  Secondary:   Number of Participants With Peripheral Blood B-Cell Depletion   [ Time Frame: Day 22 ]

20.  Secondary:   Number of Participants With Peripheral Blood B-Cell Recovery   [ Time Frame: End of last dose + 6 Months Follow-Up ]

21.  Secondary:   Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)   [ Time Frame: 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.] ]

22.  Secondary:   Number of Participants With Infusion Related Reactions   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]

23.  Secondary:   Number of Participants With Human Anti-Chimeric Antibodies (HACA)   [ Time Frame: Day 1 ]

24.  Secondary:   Number of Participants With Human Anti-Human Antibodies (HAHA)   [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
phone: 800-821-8590


No publications provided by Hoffmann-La Roche

Publications automatically indexed to this study:

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00576758     History of Changes
Other Study ID Numbers: BO21003
Study First Received: December 18, 2007
Results First Received: November 27, 2013
Last Updated: August 15, 2014
Health Authority: Canada: Health Canada