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
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: obinutuzumab (RO5072759)
Drug: rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.



Enrollment: 175
Study Start Date: January 2008
Study Completion Date: March 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: obinutuzumab (RO5072759)
1000 mg obinutuzumab intravenous (IV) infusion once a week for 4 weeks.
Other Names:
  • RO5072759
  • GA101
  • GAZYVA®
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.
Drug: rituximab
375 mg/m^2 rituximab IV infusion once a week for 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576758

  Show 71 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: February 13, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 29, 2014