Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
DRUGObinutuzumab
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.
DRUGCyclophosphamide
Cyclophosphamide 750 mg/m\^2 IV will be administered on Day 1 of each cycle during induction period.
DRUGDoxorubicin
Doxorubicin 50 mg/m\^2 IV will be administered on Day 1 of each cycle during induction period.
DRUGVincristine
Vincristine 1.4 mg/m\^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.
DRUGPrednisone
Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.
DRUGBendamustine
Bendamustine 90 mg/m\^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.
DRUGRituximab
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.
Sponsors
German Low Grade Lymphoma Study Group
Institute of Cancer Research, United Kingdom
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | Baseline up to data cut-off (up to approximately 4 years and 7 months) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival in the Overall Study Population, Investigator-Assessed | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC) | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Overall Response (Follicular Lymphoma Population), Investigator-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Overall Response (Overall Study Population), Investigator-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Complete Response (Follicular Lymphoma Population), Investigator-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Complete Response (Overall Study Population), Investigator-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Overall Response (Follicular Lymphoma Population), IRC-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Overall Response (Overall Study Population), IRC-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Complete Response (Follicular Lymphoma Population), IRC-Assessed | Baseline up to end of induction period (up to approximately 7 months) | 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. |
| Complete Response (Overall Study Population), IRC-Assessed | Baseline up to end of induction period (up to approximately 7 months)] | 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. |
| Overall Survival (Follicular Lymphoma Population) | Baseline up to 10 years | 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. |
| Overall Survival (Overall Study Population) | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Event-Free Survival (Follicular Lymphoma Population) | Baseline up to 10 years | 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. |
| Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | Baseline up to final analysis (up to 10 years) | 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). |
| Disease-Free Survival (Follicular Lymphoma Population) | From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Disease-Free Survival (Overall Study Population) | From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed | From first occurrence of documented CR or PR to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Duration of Response (DOR) (Overall Study Population), Investigator-Assessed | From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months) | 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. |
| Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population) | Baseline up to 10 years | 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. |
| Time to Next Anti-Lymphoma Treatment (Overall Study Population) | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
| Percentage of Participants With Adverse Events | Baseline up to 10 years | 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. |
| Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 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. |
| Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 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. |
| Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 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. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months) | 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. |
| Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | 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) | 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. |
| Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | 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) | 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. |
| Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase | 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) | 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. |
| Event-Free Survival (Overall Study Population) | Baseline up to data cut-off (up to approximately 5 years and 2 months) | 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. |
Countries
Australia, Belgium, Canada, China, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Japan, Russia, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 177 centers in 18 countries.
Pre-assignment details
Eleven participants withdrew from the study after randomization but prior to receiving study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab+Chemotherapy - Induction Period Participants received 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 induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. | 699 |
| Obinutuzumab+Chemotherapy - Induction Period Participants received 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 chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant was chosen by the site prior to initiation of the study. | 702 |
| Total | 1,401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Follow-Up Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Follow-Up Period | Death | 0 | 0 | 0 | 0 | 0 | 0 | 27 | 30 |
| Follow-Up Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 15 |
| Follow-Up Period | Non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 9 |
| Follow-Up Period | No reason provided | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 |
| Follow-Up Period | Other | 0 | 0 | 0 | 0 | 0 | 0 | 18 | 21 |
| Follow-Up Period | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 15 |
| Follow-Up Period | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 126 | 106 |
| Follow-Up Period | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Follow-Up Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 29 | 32 |
| Induction Period | Adverse Event | 23 | 26 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Death | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Non-compliance | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Other | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Physician Decision | 6 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Progressive Disease | 15 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Protocol Violation | 3 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Randomised but not treated | 4 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Withdrawal by Subject | 3 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Adverse Event | 0 | 0 | 53 | 66 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Death | 0 | 0 | 5 | 6 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Lost to Follow-up | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Non-compliance | 0 | 0 | 4 | 3 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Other | 0 | 0 | 4 | 7 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Physician Decision | 0 | 0 | 14 | 19 | 0 | 1 | 0 | 0 |
| Maintenance/Observation Period | Progressive Disease | 0 | 0 | 72 | 40 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Protocol Violation | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Maintenance/Observation Period | Withdrawal by Subject | 0 | 0 | 7 | 5 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Rituximab+Chemotherapy - Induction Period | Obinutuzumab+Chemotherapy - Induction Period | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 12.3 | 58.9 years STANDARD_DEVIATION 11.6 | 58.5 years STANDARD_DEVIATION 11.9 |
| Age Continuous in Follicular Lymphoma Sub-Population | 57.7 years STANDARD_DEVIATION 12.2 | 58.2 years STANDARD_DEVIATION 11.5 | 57.9 years STANDARD_DEVIATION 11.9 |
| Gender in Follicular Lymphoma Sub-Population Female | 321 Participants | 318 Participants | 639 Participants |
| Gender in Follicular Lymphoma Sub-Population Male | 280 Participants | 283 Participants | 563 Participants |
| Sex: Female, Male Female | 374 Participants | 365 Participants | 739 Participants |
| Sex: Female, Male Male | 325 Participants | 337 Participants | 662 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 111 / 692 | 104 / 698 |
| other Total, other adverse events | 675 / 692 | 690 / 698 |
| serious Total, serious adverse events | 309 / 692 | 361 / 698 |
Outcome results
Primary
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).
Time frame: Baseline up to data cut-off (up to approximately 4 years and 7 months)
Population: The intent-to-treat follicular lymphoma population (FL ITT), defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | 24.0 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | 16.8 percentage of participants with event |
p-value: 0.001295% CI: [0.51, 0.85]Log Rank
Secondary
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.
Time frame: Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months)
Population: The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Social/Family Well-being , Baseline | 22.84 units on a scale | Standard Deviation 4.92 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Cycle 3, Day 1 | -0.91 units on a scale | Standard Deviation 4.54 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, End Induction | -0.06 units on a scale | Standard Deviation 4.83 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Maint Month 2 | 0.83 units on a scale | Standard Deviation 4.76 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Maint Month 12 | 1.14 units on a scale | Standard Deviation 4.29 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, End Maint | 0.88 units on a scale | Standard Deviation 4.54 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Physical Well-being (PW), Baseline | 23.36 units on a scale | Standard Deviation 4.77 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Cycle 3 Day 1 | -0.52 units on a scale | Standard Deviation 4.03 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, End Induction | -0.46 units on a scale | Standard Deviation 4.77 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Maint Month 2 | -0.39 units on a scale | Standard Deviation 4.72 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Maint Month 12 | -0.61 units on a scale | Standard Deviation 5.56 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, End Maint | -0.93 units on a scale | Standard Deviation 5.67 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Emotional Well-being (EW), Baseline | 17.64 units on a scale | Standard Deviation 4.19 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Cycle 3 Day 1 | 1.49 units on a scale | Standard Deviation 3.4 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, End Induction | 1.16 units on a scale | Standard Deviation 3.9 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Maint Month 2 | 1.77 units on a scale | Standard Deviation 3.88 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Maint Month 12 | 1.45 units on a scale | Standard Deviation 3.92 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, End Maint | 1.43 units on a scale | Standard Deviation 3.98 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Functional Well-being (FW), Baseline | 18.66 units on a scale | Standard Deviation 6.19 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Cycle 3 Day 1 | -0.30 units on a scale | Standard Deviation 5.3 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, End Induction | 0.44 units on a scale | Standard Deviation 5.63 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Maint Month 2 | 1.04 units on a scale | Standard Deviation 5.31 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Maint Month 12 | 1.84 units on a scale | Standard Deviation 5.54 |
| Rituximab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, End Maint | 1.40 units on a scale | Standard Deviation 6.12 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Maint Month 12 | 1.65 units on a scale | Standard Deviation 5.95 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Physical Well-being (PW), Baseline | 23.14 units on a scale | Standard Deviation 4.85 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Emotional Well-being (EW), Baseline | 17.87 units on a scale | Standard Deviation 4.13 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Cycle 3, Day 1 | -0.21 units on a scale | Standard Deviation 4.59 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Functional Well-being (FW), Baseline | 18.76 units on a scale | Standard Deviation 5.98 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, End Induction | 0.56 units on a scale | Standard Deviation 5.14 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Cycle 3 Day 1 | 1.35 units on a scale | Standard Deviation 3.35 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Maint Month 2 | 1.42 units on a scale | Standard Deviation 5.09 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Maint Month 2 | 1.25 units on a scale | Standard Deviation 6.02 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, Maint Month 12 | 1.34 units on a scale | Standard Deviation 4.74 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, End Induction | 1.14 units on a scale | Standard Deviation 3.87 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | PW Change, End Maint | 1.33 units on a scale | Standard Deviation 5 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, Cycle 3 Day 1 | -0.07 units on a scale | Standard Deviation 5.24 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | Social/Family Well-being , Baseline | 23.28 units on a scale | Standard Deviation 4.77 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Maint Month 2 | 1.49 units on a scale | Standard Deviation 4.16 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Cycle 3 Day 1 | -0.67 units on a scale | Standard Deviation 3.92 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, End Maint | 1.72 units on a scale | Standard Deviation 6.16 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, End Induction | -0.56 units on a scale | Standard Deviation 5 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, Maint Month 12 | 1.46 units on a scale | Standard Deviation 3.88 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Maint Month 2 | -0.67 units on a scale | Standard Deviation 4.68 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | FW Change, End Induction | 0.93 units on a scale | Standard Deviation 5.85 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, Maint Month 12 | -0.97 units on a scale | Standard Deviation 5.34 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | EW Change, End Maint | 1.49 units on a scale | Standard Deviation 3.99 |
| Obinutuzumab+Chemotherapy | Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population) | S/FW Change, End Maint | -0.71 units on a scale | Standard Deviation 5.54 |
Secondary
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.
Time frame: 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)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase | Change Baseline, Follow-Up Month 36 | 0.05 units on a scale | Standard Deviation 0.24 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase | Change Baseline, Follow-Up Month 48 | 0.05 units on a scale | Standard Deviation 0.2 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase | Change Baseline, Follow-Up Month 36 | 0.06 units on a scale | Standard Deviation 0.23 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase | Change Baseline, Follow-Up Month 48 | 0.06 units on a scale | Standard Deviation 0.23 |
Secondary
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.
Time frame: 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)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Maint/Obs Month 2 | 0.05 units on a scale | Standard Deviation 0.23 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Induction Compl | 0.04 units on a scale | Standard Deviation 0.23 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change from Baseline, Maint/Obs Month 12 | 0.00 units on a scale | Standard Deviation 0 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Cycle 3 Day 1 | 0.03 units on a scale | Standard Deviation 0.21 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Baseline Induction | 0.80 units on a scale | Standard Deviation 0.24 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change from Baseline, Maint/Obs Month 12 | -0.20 units on a scale | — |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Maint/Obs Completion | -0.10 units on a scale | — |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Baseline Induction | 0.81 units on a scale | Standard Deviation 0.21 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Cycle 3 Day 1 | 0.03 units on a scale | Standard Deviation 0.2 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Induction Compl | 0.03 units on a scale | Standard Deviation 0.22 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase | Change Baseline, Maint/Obs Month 2 | 0.06 units on a scale | Standard Deviation 0.22 |
Secondary
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.
Time frame: 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)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Month 2 | 0.04 units on a scale | Standard Deviation 0.34 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Month 12 | 0.06 units on a scale | Standard Deviation 0.24 |
| Rituximab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Completion | 0.03 units on a scale | Standard Deviation 0.23 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Month 2 | 0.04 units on a scale | Standard Deviation 0.14 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Month 12 | 0.06 units on a scale | Standard Deviation 0.21 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase | Change Baseline, Maint/Obs Completion | 0.05 units on a scale | Standard Deviation 0.23 |
Secondary
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.
Time frame: Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months)
Population: The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma, Baseline | 45.01 units on a scale | Standard Deviation 9.37 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Cycle 3 Day 1 | 2.04 units on a scale | Standard Deviation 7.18 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, End Induction | 2.99 units on a scale | Standard Deviation 8.63 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Maint Month 2 | 4.80 units on a scale | Standard Deviation 8.29 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Maint Month 12 | 4.93 units on a scale | Standard Deviation 8.34 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, End Maint | 4.31 units on a scale | Standard Deviation 8.81 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Maint Month 12 | 4.27 units on a scale | Standard Deviation 8.31 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma, Baseline | 45.54 units on a scale | Standard Deviation 9.29 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Maint Month 2 | 4.52 units on a scale | Standard Deviation 8.32 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, Cycle 3 Day 1 | 2.71 units on a scale | Standard Deviation 7.46 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, End Maint | 4.57 units on a scale | Standard Deviation 8.54 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population) | Lymphoma Change, End Induction | 3.01 units on a scale | Standard Deviation 8.36 |
Secondary
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.
Time frame: Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months)
Population: The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score, Baseline | 86.61 units on a scale | Standard Deviation 18.16 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Cycle 3 Day 1 | 0.46 units on a scale | Standard Deviation 15.03 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, End Induction | 2.91 units on a scale | Standard Deviation 17 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Maint M2 | 6.22 units on a scale | Standard Deviation 16.16 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Maint M12 | 7.61 units on a scale | Standard Deviation 15.62 |
| Rituximab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, End Maint | 6.23 units on a scale | Standard Deviation 17.06 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Maint M12 | 7.20 units on a scale | Standard Deviation 16.75 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score, Baseline | 86.94 units on a scale | Standard Deviation 18.05 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Maint M2 | 7.17 units on a scale | Standard Deviation 16.57 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, Cycle 3 Day 1 | 2.18 units on a scale | Standard Deviation 15.95 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, End Maint | 7.44 units on a scale | Standard Deviation 16.96 |
| Obinutuzumab+Chemotherapy | Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population) | TOI Score Change, End Induction | 4.57 units on a scale | Standard Deviation 16.71 |
Secondary
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.
Time frame: Baseline (Induction Cycle 1, Day 1), data cut-off (up to approximately 5 years and 2 months)
Population: The FL ITT population was defined as all randomized participants with follicular histology grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score, Baseline | 127.40 units on a scale | Standard Deviation 22.43 |
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Cycle 3 Day 1 | 1.98 units on a scale | Standard Deviation 17.01 |
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, End Induction | 4.18 units on a scale | Standard Deviation 19.75 |
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Maint Month 2 | 8.40 units on a scale | Standard Deviation 19.16 |
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Maint Month 12 | 8.87 units on a scale | Standard Deviation 19.31 |
| Rituximab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, End Maint | 7.43 units on a scale | Standard Deviation 19.88 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Maint Month 12 | 7.90 units on a scale | Standard Deviation 19.55 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score, Baseline | 128.42 units on a scale | Standard Deviation 22.16 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Maint Month 2 | 8.13 units on a scale | Standard Deviation 19.8 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, Cycle 3 Day 1 | 3.21 units on a scale | Standard Deviation 17.12 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, End Maint | 8.80 units on a scale | Standard Deviation 20.57 |
| Obinutuzumab+Chemotherapy | Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population) | Total Score Change, End Induction | 5.10 units on a scale | Standard Deviation 20.03 |
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Complete Response (Follicular Lymphoma Population), Investigator-Assessed | Without PET | 24.1 percentage of participants with event |
| Rituximab+Chemotherapy | Complete Response (Follicular Lymphoma Population), Investigator-Assessed | With PET | 56.7 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Follicular Lymphoma Population), Investigator-Assessed | Without PET | 18.6 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Follicular Lymphoma Population), Investigator-Assessed | With PET | 62.0 percentage of participants with event |
Comparison: Without PETp-value: 0.0295% CI: [-10.2, -0.78]Log Rank
Comparison: With PETp-value: 0.3295% CI: [-2.8, 13.3]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Complete Response (Follicular Lymphoma Population), IRC-Assessed | Without PET | 26.8 percentage of participants with event |
| Rituximab+Chemotherapy | Complete Response (Follicular Lymphoma Population), IRC-Assessed | With PET | 59.7 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Follicular Lymphoma Population), IRC-Assessed | Without PET | 28.5 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Follicular Lymphoma Population), IRC-Assessed | With PET | 71.4 percentage of participants with event |
Comparison: Without PETp-value: 0.5895% CI: [-3.5, 6.8]Log Rank
p-value: 0.00695% CI: [3.9, 19.4]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Complete Response (Overall Study Population), Investigator-Assessed | Without PET | 23.3 percentage of participants with event |
| Rituximab+Chemotherapy | Complete Response (Overall Study Population), Investigator-Assessed | With PET | 57.0 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Overall Study Population), Investigator-Assessed | Without PET | 18.4 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Overall Study Population), Investigator-Assessed | With PET | 61.1 percentage of participants with event |
Comparison: Without PETp-value: 0.0295% CI: [-9.3, 0.6]Log Rank
Comparison: With PETp-value: 0.3395% CI: [-3.6, 11.8]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)]
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Complete Response (Overall Study Population), IRC-Assessed | Without PET | 26.3 percentage of participants with event |
| Rituximab+Chemotherapy | Complete Response (Overall Study Population), IRC-Assessed | With PET | 59.4 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Overall Study Population), IRC-Assessed | Without PET | 27.1 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Complete Response (Overall Study Population), IRC-Assessed | With PET | 69.5 percentage of participants with event |
Comparison: Without PETp-value: 0.895% CI: [-4, 5.5]Log Rank
Comparison: With PETp-value: 0.00995% CI: [2.6, 17.6]Log Rank
Secondary
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.
Time frame: From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months)
Population: Participants with CR within the FL ITT population were included in the analysis.The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Disease-Free Survival (Follicular Lymphoma Population) | 27.9 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Disease-Free Survival (Follicular Lymphoma Population) | 26.3 percentage of participants with event |
95% CI: [0.71, 1.27]Log Rank
Secondary
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.
Time frame: From first occurrence of documented CR to data cut-off (up to approximately 5 years and 2 months)
Population: Participants with CR within the ITT population were included in the analysis.The ITT population was defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Disease-Free Survival (Overall Study Population) | 14.9 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Disease-Free Survival (Overall Study Population) | 11.2 percentage of participants with event |
95% CI: [0.5, 1.19]
Secondary
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.
Time frame: From first occurrence of documented CR or PR to data cut-off (up to approximately 5 years and 2 months)
Population: Participants with CR or PR within the FL ITT population were included in the analysis.The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed | 39.3 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed | 33.3 percentage of participants with event |
95% CI: [0.63, 0.93]Log Rank
Secondary
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.
Time frame: From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months)
Population: Participants with CR or PR within the ITT population were included in the analysis. The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Duration of Response (DOR) (Overall Study Population), Investigator-Assessed | 25.5 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Duration of Response (DOR) (Overall Study Population), Investigator-Assessed | 18.7 percentage of participants with event |
95% CI: [0.55, 0.88]
Secondary
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.
Time frame: Baseline up to 10 years
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Event-Free Survival (Follicular Lymphoma Population) | 42.9 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Event-Free Survival (Follicular Lymphoma Population) | 35.8 percentage of participants with event |
p-value: 0.001595% CI: [0.62, 0.89]Log Rank
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Event-Free Survival (Overall Study Population) | 30.6 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Event-Free Survival (Overall Study Population) | 22.6 percentage of participants with event |
p-value: 0.000495% CI: [0.56, 0.85]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Overall Response (Follicular Lymphoma Population), Investigator-Assessed | Without PET | 86.4 percentage of participants with event |
| Rituximab+Chemotherapy | Overall Response (Follicular Lymphoma Population), Investigator-Assessed | With PET | 81.2 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Follicular Lymphoma Population), Investigator-Assessed | Without PET | 88.2 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Follicular Lymphoma Population), Investigator-Assessed | With PET | 85.5 percentage of participants with event |
Comparison: Without PETp-value: 0.395% CI: [-2.02, 5.68]Log Rank
Comparison: With PETp-value: 0.1795% CI: [-1.8, 10.5]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Overall Response (Follicular Lymphoma Population), IRC-Assessed | Without PET | 88.0 percentage of participants with event |
| Rituximab+Chemotherapy | Overall Response (Follicular Lymphoma Population), IRC-Assessed | With PET | 85.2 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Follicular Lymphoma Population), IRC-Assessed | Without PET | 91.3 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Follicular Lymphoma Population), IRC-Assessed | With PET | 88.6 percentage of participants with event |
Comparison: Without PETp-value: 0.05295% CI: [-0.19, 6.85]Log Rank
Comparison: With PETp-value: 0.395% CI: [-2.3, 8.9]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Overall Response (Overall Study Population), Investigator-Assessed | Without PET | 85.7 percentage of participants with event |
| Rituximab+Chemotherapy | Overall Response (Overall Study Population), Investigator-Assessed | With PET | 81.8 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Overall Study Population), Investigator-Assessed | Without PET | 87.3 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Overall Study Population), Investigator-Assessed | With PET | 85.4 percentage of participants with event |
Comparison: Without PETp-value: 0.3395% CI: [-2, 5.3]Log Rank
Comparison: With PETp-value: 0.1795% CI: [-2.3, 9.4]Log Rank
Secondary
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.
Time frame: Baseline up to end of induction period (up to approximately 7 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab+Chemotherapy | Overall Response (Overall Study Population), IRC-Assessed | Without PET | 86.7 percentage of participants with event |
| Rituximab+Chemotherapy | Overall Response (Overall Study Population), IRC-Assessed | With PET | 83.3 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Overall Study Population), IRC-Assessed | Without PET | 89.9 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Response (Overall Study Population), IRC-Assessed | With PET | 87.2 percentage of participants with event |
Comparison: Without PETp-value: 0.04995% CI: [-0.3, 6.6]Log Rank
Comparison: With PETp-value: 0.2295% CI: [-1.7, 9.5]Log Rank
Secondary
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.
Time frame: Baseline up to 10 years
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Overall Survival (Follicular Lymphoma Population) | 14.3 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Survival (Follicular Lymphoma Population) | 12.6 percentage of participants with event |
p-value: 0.357795% CI: [0.63, 1.18]Log Rank
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Overall Survival (Overall Study Population) | 10.2 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Overall Survival (Overall Study Population) | 8.4 percentage of participants with event |
p-value: 0.2595% CI: [0.58, 1.16]Log Rank
Secondary
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.
Time frame: Baseline up to 10 years
Population: The safety analysis population included all participants who received any amount of any study drug and participants were analyzed according to the treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Percentage of Participants With Adverse Events | 99.6 percentage of participants |
| Obinutuzumab+Chemotherapy | Percentage of Participants With Adverse Events | 99.9 percentage of participants |
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed | 23.5 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed | 18.0 percentage of participants with event |
p-value: 0.011895% CI: [0.56, 0.93]Log Rank
Secondary
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).
Time frame: Baseline up to final analysis (up to 10 years)
Population: The FL ITT population was defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | 40.6 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed | 34.3 percentage of participants with event |
p-value: 0.005595% CI: [0.64, 0.93]Log Rank
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Progression-Free Survival in the Overall Study Population, Investigator-Assessed | 41.5 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Progression-Free Survival in the Overall Study Population, Investigator-Assessed | 34.8 percentage of participants with event |
p-value: 0.002895% CI: [0.65, 0.91]Log Rank
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC) | 24.6 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC) | 18.4 percentage of participants with event |
p-value: 0.003895% CI: [0.57, 0.9]Log Rank
Secondary
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.
Time frame: Baseline up to 10 years
Population: The FL ITT population, defined as all randomized participants with follicular histology, where participants were grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population) | 34.8 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population) | 26.6 percentage of participants with event |
p-value: 0.00195% CI: [0.58, 0.87]Log Rank
Secondary
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.
Time frame: Baseline up to data cut-off (up to approximately 5 years and 2 months)
Population: The ITT population defined as all randomized participants grouped according to their randomized treatment arm regardless of what treatments were actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+Chemotherapy | Time to Next Anti-Lymphoma Treatment (Overall Study Population) | 21.6 percentage of participants with event |
| Obinutuzumab+Chemotherapy | Time to Next Anti-Lymphoma Treatment (Overall Study Population) | 15.7 percentage of participants with event |
p-value: 0.00495% CI: [0.54, 0.89]Log Rank