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: February 13, 2014
Last verified: February 2014

December 18, 2007
February 13, 2014
January 2008
September 2011   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]

Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigator at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL.

CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow.

PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

Phase 1: Incidence of dose-limiting toxicity. Phase 2: Overall response rate.
Complete list of historical versions of study NCT00576758 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
    Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. CR is defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL. All lymph nodes and nodal masses must have regressed to normal size. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Other organs considered to be enlarged before therapy due to involvement by lymphoma, such as liver and kidneys, must have decreased in size. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
  • 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) ] [ Designated as safety issue: No ]
    Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson. PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.
  • 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) ] [ Designated as safety issue: No ]

    Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

    CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL.

    CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow.

    PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

  • 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) ] [ Designated as safety issue: No ]
    Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators at end of induction treatment. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.
  • 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) ] [ Designated as safety issue: No ]

    Overall response was defined as Complete Response (CR), Complete Response/Unconfirmed (CRu) or Partial Response (PR) as assessed by investigators during study treatment (induction or extended treatment phase). Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

    CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL.

    CRu was CR plus one or more of the following: A residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameter (tumors)(SPD) and/or indeterminate bone marrow.

    PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

  • Progression-Free Survival (PFS) [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ] [ Designated as safety issue: No ]

    PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the Investigator.

    Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

    Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

  • Percentage of Participants With Progression-Free Survival (PFS) Events [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ] [ Designated as safety issue: No ]

    The percentage of participants with progression, relapse, or death events from any cause as assessed by the Investigator.

    Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

    Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

  • Event Free Survival [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ] [ Designated as safety issue: No ]

    Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy.

    Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

    Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

  • Percentage of Participants With Event Free Survival (EFS) Events [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ] [ Designated as safety issue: No ]

    Percentage of participants with Event Free Events: disease progression/relapse, death, or start of a new anti-leukemic therapy.

    Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

    Relapse was defined as the appearance of any new lesion or increase by ≥ 50% in the size of previously involved sites and/or a ≥ 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node.

  • Duration of Response [ Time Frame: Randomization to Clinical cutoff: 07 March 2013 (Up to 43.2 months) ] [ Designated as safety issue: No ]

    Duration of Response was defined as the date the response, either Complete Response (CR) or Partial Response (PR), was first recorded until the date of Disease Progression or death due to any cause. Computed tomography imaging was used for the primary assessment of tumor response per 1999 criteria by Cheson.

    CR was defined as the disappearance of all clinical and radiographic evidence of disease, disease-related symptoms and normalization of biochemical abnormalities of NHL.

    PR was defined as 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. No new sites of disease.

    Disease Progression was defined as a ≥ 50% increase from nadir in the SPD of any previously identified abnormal node and/or the appearance of any new lesion during or at the end of therapy.

Efficacy: Complete and partial response rates; progression-free survival, event-free survival, duration of response (Phase II only). Safety: AEs, laboratory parameters, Pk and Pd parameters.
Not Provided
Not Provided
 
GAUSS: A Study of Obinutuzumab (RO5072759) in Patients With Indolent Non-Hodgkin's Lymphoma
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-Hodgkin's Lymphoma
  • Drug: obinutuzumab (RO5072759)
    1000 mg obinutuzumab intravenous (IV) infusion once a week for 4 weeks.
    Other Names:
    • RO5072759
    • GA101
    • GAZYVA®
  • Drug: rituximab
    375 mg/m^2 rituximab IV infusion once a week for 4 weeks.
  • Experimental: 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.
    Intervention: Drug: obinutuzumab (RO5072759)
  • Active Comparator: 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.
    Intervention: Drug: rituximab
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. Epub 2012 Mar 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
175
March 2013
September 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Austria,   Belgium,   Brazil,   Canada,   Croatia,   Denmark,   Greece,   Italy,   Netherlands,   Poland,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
 
NCT00576758
BO21003
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP