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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01332968




Registration number
NCT01332968
Ethics application status
Date submitted
8/04/2011
Date registered
11/04/2011
Date last updated
30/06/2020

Titles & IDs
Public title
A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)
Scientific title
A Multicenter, Phase III, Open-Label, Randomized Study in Previously Untreated Patients With Advanced Indolent Non-Hodgkin's Lymphoma Evaluating the Benefit of GA101 (RO5072759) Plus Chemotherapy Compared With Rituximab Plus Chemotherapy Followed by GA101 or Rituximab Maintenance Therapy in Responders
Secondary ID [1] 0 0
2010-024132-41
Secondary ID [2] 0 0
BO21223
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone
Treatment: Drugs - Bendamustine
Treatment: Drugs - Rituximab

Active Comparator: Rituximab+Chemotherapy - Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.

Experimental: Obinutuzumab+Chemotherapy - Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.


Treatment: Drugs: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

Treatment: Drugs: Doxorubicin
Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

Treatment: Drugs: Vincristine
Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.

Treatment: Drugs: Prednisone
Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.

Treatment: Drugs: Bendamustine
Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.

Treatment: Drugs: Rituximab
Rituximab 375 milligrams per square meter (mg/m^2) IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed - Progression-free survival in participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).
Timepoint [1] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [1] 0 0
Progression-Free Survival in the Overall Study Population, Investigator-Assessed - Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Timepoint [1] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [2] 0 0
Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed - Progression-free survival in the participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. In the first 170 patients with follicular lymphoma, an FDG-PET was mandatory where a PET scanner was available.
Timepoint [2] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [3] 0 0
Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC) - Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Timepoint [3] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [4] 0 0
Overall Response (Follicular Lymphoma Population), Investigator-Assessed - Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with and without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.
Timepoint [4] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [5] 0 0
Overall Response (Overall Study Population), Investigator-Assessed - Overall response in the overall study population was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without positron emission tomography (PET). CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.
Timepoint [5] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [6] 0 0
Complete Response (Follicular Lymphoma Population), Investigator-Assessed - Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Timepoint [6] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [7] 0 0
Complete Response (Overall Study Population), Investigator-Assessed - Percentage of participants with complete response in the overall study population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Timepoint [7] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [8] 0 0
Overall Response (Follicular Lymphoma Population), IRC-Assessed - Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.
Timepoint [8] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [9] 0 0
Overall Response (Overall Study Population), IRC-Assessed - Overall response in the overall study population was defined as percentage of participants with PR or CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.
Timepoint [9] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [10] 0 0
Complete Response (Follicular Lymphoma Population), IRC-Assessed - Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Timepoint [10] 0 0
Baseline up to end of induction period (up to approximately 7 months)
Secondary outcome [11] 0 0
Complete Response (Overall Study Population), IRC-Assessed - Percentage of participants with complete response in the overall study population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.
Timepoint [11] 0 0
Baseline up to end of induction period (up to approximately 7 months)]
Secondary outcome [12] 0 0
Overall Survival (Follicular Lymphoma Population) - Overall survival in the follicular lymphoma population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.
Timepoint [12] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [13] 0 0
Overall Survival (Overall Study Population) - Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.
Timepoint [13] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [14] 0 0
Event-Free Survival (Follicular Lymphoma Population) - Event-free survival in the follicular lymphoma population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with an event.
Timepoint [14] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [15] 0 0
Event-Free Survival (Overall Study Population) - Event-free survival in the overall study population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with event.
Timepoint [15] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [16] 0 0
Disease-Free Survival (Follicular Lymphoma Population) - Disease-free survival in the follicular lymphoma population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma (RRCML). Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.
Timepoint [16] 0 0
From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [17] 0 0
Disease-Free Survival (Overall Study Population) - Disease-free survival in the overall study population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.
Timepoint [17] 0 0
From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [18] 0 0
Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed - DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR any time prior to NALT based on RRCML. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. PR was defined as >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Timepoint [18] 0 0
From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [19] 0 0
Duration of Response (DOR) (Overall Study Population), Investigator-Assessed - DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR any time prior to NALT based on RRCML. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. PR was defined as >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Timepoint [19] 0 0
From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [20] 0 0
Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population) - Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of participants with event.
Timepoint [20] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months
Secondary outcome [21] 0 0
Time to Next Anti-Lymphoma Treatment (Overall Study Population) - Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of participants with event.
Timepoint [21] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [22] 0 0
Percentage of Participants With Adverse Events - An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Timepoint [22] 0 0
Baseline up to data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [23] 0 0
Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) - FACT-G consists of the following 4 FACT-Lym sub-questionnaires: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24) and Functional Well-being (range: 0-28). Higher scores indicate better outcomes. A positive change from baseline indicates improvement. Maint = Maintenance period.
Timepoint [23] 0 0
Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [24] 0 0
Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) - The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Timepoint [24] 0 0
Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [25] 0 0
Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) - The FACT-Lym Individual Subscale Lymphoma Score for the follicular lymphoma population was derived from the Lymphoma subscale questionnaire (range: 0-60). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Timepoint [25] 0 0
Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [26] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) - The FACT-Lym Total Score for the follicular lymphoma population was derived from the following 5 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24),Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym Total Score is the sum of all 5 individual subscales (range 0-168). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.
Timepoint [26] 0 0
Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 4 years and 7 months)
Secondary outcome [27] 0 0
Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase - The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Completion (Compl) includes completion visit and early termination visit. Maintenance/Observation is indicated as Maint/Obs.
Timepoint [27] 0 0
Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 months after Day 1 of last induction cycle, Follow-up: every year up to data cut-off (up to 4 years and 7 months)
Secondary outcome [28] 0 0
Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase - The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1 Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs. Completion includes completion visit and early termination visit.
Timepoint [28] 0 0
Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 months after Day 1 of last induction cycle, Follow-up: every year up to data cut-off (up to 4 years and 7 months)
Secondary outcome [29] 0 0
Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase - The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs in data categories. Completion includes completion visit and early termination visit.
Timepoint [29] 0 0
Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months); Maintenance: 2, 12 after Day 1 of last induction cycle, Follow-up: every year for up to data cut-off (up to 4 years and 7 months)

Eligibility
Key inclusion criteria
- Cluster of differentiation 20 (CD20)-positive indolent B-cell non-Hodgkin's lymphoma
(follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma)

- Stage III or IV disease, or Stage II bulky disease (defined as tumor diameter greater
than or equal to [>/=] 7 centimeters [cm])

- For participants with follicular lymphoma: requirement for treatment according to
Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria

- For participants with symptomatic splenic, nodal, or non-gastric extranodal marginal
zone lymphoma: disease that is de novo or has relapsed following local therapy (i.e.
surgery or radiotherapy) and requires therapy as assessed by the investigator

- At least one bi-dimensionally measurable lesion (greater than [>] 2 cm in its largest
dimension by computed tomography [CT] scan or magnetic resonance imaging [MRI])

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

- Adequate hematologic function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of
transformation to a high-grade or diffuse large B-cell lymphoma

- Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's
macroglobulinaemia

- Ann Arbor Stage I disease

- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

- Known hypersensitivity to any of the study drugs or sensitivity to murine products, or
history of sensitivity to mannitol

- For participants with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma
with chemotherapy, immunotherapy, or radiotherapy

- For participants with non-follicular lymphoma: prior treatment with chemotherapy or
immunotherapy

- Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle
1

- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results

- For participants who will be receiving cyclophosphamide, doxorubicin, vincristine, and
prednisone (CHOP): left ventricular ejection fraction (LVEF) less than (<) 50% by
multiple-gated acquisition (MUGA) scan or echocardiogram

- History of prior other malignancy with the exception of curatively treated basal or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time
prior to study

- Known active infection, or major episode of infection within 4 week prior to the start
of Cycle 1

- Vaccination with a live vaccine within 28 days prior to randomization

- Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for
diagnosis

- Abnormal laboratory values as defined by protocol for creatinine, creatinine
clearance, aspartate transaminase (AST) or alanine transaminase (ALT), total
bilirubin, international normalized ration (INR), partial thromboplastin time (PTT) or
activated partial thromboplastin time (aPPT), unless these abnormalities are due to
underlying lymphoma

- Positive test results for human immunodeficiency virus (HIV), human T-lymphotropic
virus 1 (HTLV1), hepatitis C or chronic hepatitis B

- Pregnant or lactating women

- Life expectancy <12 months

- Participation in another clinical trial with drug intervention within 28 days prior to
start of Cycle 1 and during study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital; Haematology - Sydney
Recruitment hospital [2] 0 0
Westmead Hospital; Haematology - Sydney
Recruitment hospital [3] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [4] 0 0
St Vincent'S Hospital; Haematology - Fitzroy
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre; Department of Haematology - Melbourne
Recruitment hospital [6] 0 0
Austin and Repatriation Medical Centre; Cancer Services - Melbourne
Recruitment hospital [7] 0 0
Monash Medical Centre; Haematology - Melbourne
Recruitment hospital [8] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2139 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
German Low Grade Lymphoma Study Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Institute of Cancer Research, United Kingdom
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This open-label, randomized study will assess the efficacy and safety of obinutuzumab
(RO5072759) in combination with chemotherapy compared to rituximab (MabThera/Rituxan) with
chemotherapy followed by obinutuzumab or rituximab maintenance in participants with untreated
advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, participants
achieving response (Complete response [CR] or partial response [PR]) will undergo a
maintenance period continuing on the randomized antibody treatment alone every 2 months until
disease progression for a total of 2 years. Anticipated time on study treatment is up to
approximately 2.5 years. After maintenance or observation, participants will be followed for
5 years until progression. After progression, participants will be followed for new
anti-lymphoma therapy and overall survival until the end of the study.
Trial website
https://clinicaltrials.gov/show/NCT01332968
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications