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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Obinutuzumab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone
* Drug: Bendamustine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rituximab+Chemotherapy<br>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. | Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Doxorubicin<br>* Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Vincristine<br>* Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Prednisone<br>* Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.<br>Drug: Bendamustine<br>* Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.<br>Drug: Rituximab<br>* 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.<br>* Other names: MabThera/Rituxan;|
| Experimental: Obinutuzumab+Chemotherapy<br>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. | Drug: Obinutuzumab<br>* 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.<br>* Other names: GA101; RO5072759;Drug: Cyclophosphamide<br>* Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Doxorubicin<br>* Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Vincristine<br>* Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.<br>Drug: Prednisone<br>* Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.<br>Drug: Bendamustine<br>* Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline up to data cut-off (up to approximately 4 years and 7 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline up to final analysis (up to 10 years) | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months) | 
| 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. | Baseline up to end of induction period (up to approximately 7 months)] | 
| 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. | Baseline up to 10 years | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline up to 10 years | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | From first occurrence of documented CR or PR to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months) | 
| 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. | Baseline up to 10 years | 
| 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. | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline up to 10 years | 
| 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. | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 
| 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. | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 
| 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. | 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 5 years and 2 months) | 
| 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. | 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 5 years and 2 months) | 
| 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. | 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 5 years and 2 months) |