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A Study of Obinutuzumab + Bendamustine (BG) in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02320487
Collaborator
(none)
102
Enrollment
26
Locations
1
Arm
46.3
Actual Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2, open-label, multicenter study to evaluate the safety and efficacy of BG induction therapy in participants with previously untreated CLL. The anticipated time on study treatment is 24 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
102 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Open-Label Study of Obinutuzumab Plus Bendamustine (BG) in Patients With Previously Untreated Chronic Lymphocytic Leukemia
Actual Study Start Date :
Mar 31, 2015
Actual Primary Completion Date :
Nov 7, 2016
Actual Study Completion Date :
Feb 6, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Obinutuzumab + Bendamustine (BG)

Participants received obinutuzumab + bendamustine (BG) induction therapy in 28-day cycles for 6 cycles.

Drug: Bendamustine
Bendamustine was administered as an intravenous infusion at a dose of 90 milligrams per square meter (mg/m^2) on Days 2 and 3 Cycle 1; and on Days 1 and 2 Cycles 2-6.
Other Names:
  • Treanda
  • Levact

    • Drug: Obinutuzumab
    Obinutuzumab was administered as an intravenous infusion at a dose of 100 milligrams (mg) on Day 1 Cycle 1; at a dose of 900 mg on Day 2 Cycle 1; at a dose of 1000 mg on Days 8 and 15 Cycle 1, and Day 1 Cycles 2-6.
    Other Names:
  • GA101
  • Gazyva™
  • RO5072759

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Complete Response (CR), as Determined by the Investigator Using International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) Guidelines [2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)]

      The CR rate was defined as CR or CR with incomplete blood count recovery (CRi), assessed by the investigator according to iwCLL NCI-WG criteria. The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes < 4 times 10^9 cells/L; absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to CLL involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L, and hemoglobin > 11.0 g/dL; normocellular BM aspirate with < 30% lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. Those fulfilling CR criteria but who have persistent anemia, thrombocytopenia, or neutropenia were considered CRi.

    Secondary Outcome Measures

    1. Percentage of Participants With Objective Response of CR or Partial Response (PR) at the End of Induction Therapy, as Determined by the Investigator Using iwCLL NCI-WG Guidelines [2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)]

      CR is defined in the previous outcome measure. The definition of PR required that the following be documented for minimum 2 months: >/= 50% decrease in peripheral blood lymphocytes from Baseline; reduction in lymphadenopathy; >/= 50% reduction in spleen or liver enlargement; and CBC with one of the following without need for transfusion or exogenous growth factors: polymorphonuclear leukocytes >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L or >/= 50% improvement from Baseline, or hemoglobin > 11.0 g/dL or >/= 50% improvement from Baseline.

    2. Duration of Response Among Participants With Objective Response of CR or PR, as Determined by the Investigator Using iwCLL NCI-WG Guidelines [From the first assessment of CR, CRi, PR, or nPR (at up to approximately 228 to 258 days) until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)]

      Duration of response was defined as the time from the first assessment of CR, CRi, PR, or nodular partial response (nPR) to the first documentation of PD or death, whichever occurred first. CR, CRi, and PR are identified in previous outcome measures. Participants with lymphoid nodules who otherwise met CR criteria were considered nPR. Participants with post-baseline response assessments (excluding progressive disease) but with no end-of-induction treatment response available were censored on Day 1, and those with end-of-induction treatment response available but who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

    3. Progression-Free Survival (PFS), as Determined by the Investigator Using iwCLL NCI-WG Guidelines [Day 1 until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)]

      PFS was defined as the time from the start of induction treatment (Day 1) to the first occurrence of disease progression, relapse as determined by the investigator using iwCLL NCI WG guidelines, or death (within 28 days after the last dose of study drug), whichever occurred first. Disease progression: at least one of the following: lymphadenopathy; increase in the liver or spleen size by 50% or more or the appearance of hepatomegaly or splenomegaly; an increase in the number of blood lymphocytes by 50% or more with at least 5000 B lymphocytes per microliter; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL. Relapse: Having achieved CR or PR, but after a period of 6 or more months, having demonstrated evidence of disease progression. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

    4. Overall Survival (OS) [Day 1 until death from any cause (up to 46 months)]

      OS was defined as the time from the start of induction treatment to death from any cause. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.

    5. Percentage of Participants Who Achieved Minimal Residual Disease (MRD)-Negative Status in Bone Marrow at Any Time During the Study [Up to 46 months]

      MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in bone marrow aspirate. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.

    6. Percentage of Participants Who Achieved MRD-Negative Status in Peripheral Blood at Any Time During the Study [Baseline up to 46 months]

      MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.

    7. Time to MRD-Negative Status in Peripheral Blood [Baseline up to 46 months]

      MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity if the value is <10^-4 (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Time to MRD-negative status is defined as the time between MRD positivity (>= 10^-4) or the time of first dose treatment for patients who were missing MRD status assessment at baseline to the first achievement of MRD negativity in the peripheral blood.

    8. Duration of MRD-Negativity in Peripheral Blood Among Participants Who Achieved MRD-Negative Status [Baseline up to 46 months]

      MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Duration of MRD-negativity among patients who achieved MRD negativity in the study is defined as the period between the first occurrence of MRD-negative status and a subsequent MRD-positive status.

    9. Minimum Observed Concentration (Ctrough) of Obinutuzumab After Cycle 2 [Pre-infusion (0 hours) on Day 1 Cycle 3 (1 cycle = 28 days)]

      Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.

    10. Ctrough of Obinutuzumab After Cycle 4 [Pre-infusion (0 hours) on Day 1 Cycle 5 (1 cycle = 28 days)]

      Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.

    11. Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score [Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)]

      The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.

    12. Change From Baseline in the EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) Score [Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)]

      The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) module included assessments of fatigue, treatment side effects, disease symptoms, infection, social activities, and future health worries. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.

    13. Number of Hospitalizations Due to Adverse Events (AEs) [Day 1 up to 46 months]

      An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.

    14. Percentage of Participants With Adverse Events (AEs) [Day 1 up to 46 months]

      An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants must satisfy one of the criteria for treatment initiation, as outlined in the iwCLL NCI-WG guidelines. The criteria include: (a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia, (b) Massive (i.e., greater than or equal to [>=] 6 centimeters [cm] below the left costal margin) or progressive or symptomatic splenomegaly, (c) Massive nodes (i.e., >= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy, (d) Progressive lymphocytosis with an increase of greater than (>) 50 percent (%) over a 2-month period or lymphocyte doubling time (LDT) of less than (<) 6 months, (e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, (f) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of >=10% within the previous 6 months, significant fatigue (i.e., Eastern Cooperative Oncology Group Performance Status [ECOG PS] of 2 or worse or the inability to work or perform usual activities), fevers higher than 100.5 degrees Fahrenheit (°F)/38.0 degrees Celsius (°C) for >= 2 weeks without other evidence of infection, or night sweats for >1 month without evidence of infection

    • Absolute neutrophil count (ANC) >=1.5 × 109 per liter (/L) and platelets >=75 × 109/L unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)

    • Life expectancy >6 months

    • ECOG PS of 0, 1, or 2

    • Willing to use acceptable contraceptive measures as defined by the protocol during and at least for 6 months (male participants) or 12 months (female participants) after the last dose of study drug

    Exclusion Criteria:

    • Pregnant or lactating, or intending to become pregnant during the study: Women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

    • Participants who have received previous CLL therapy, including investigational therapies

    • Transformation of CLL to aggressive non-Hodgkin's lymphoma (Richter's transformation)

    • Inadequate renal function

    • Inadequate liver function: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >5× upper limit of normal [ULN] for >2 weeks; bilirubin >3× ULN) unless due to underlying disease

    • History of other malignancy, which could affect compliance with the protocol or interpretation of results

    • Participants with active bacterial, viral, or fungal infection requiring systemic treatment

    • Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)

    • Positive hepatitis serology: (a) Participants with positive serology for hepatitis B, defined as positivity for hepatitis B surface antigen (HBsAg), or participants who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive, (b) Participants positive for anti-HBc, but with negative hepatitis B Virus (HBV) deoxyribonucleic acid (DNA), will be considered for inclusion by the Medical Monitor on a case-by-case basis in order to ensure feasibility of monthly DNA testing and availability of appropriate care in case of hepatitis B reactivation, (c) Participants with positive serology for hepatitis C (HCV) unless HCV (by ribonucleic acid [RNA]) is confirmed negative

    • History of severe allergic or anaphylactic reactions to monoclonal antibodies

    • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm)

    • Vaccination with a live vaccine a minimum of 30 days prior to study treatment

    • Use of investigational agents of any kind within 30 days before study treatment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute Huntsville Alabama United States 35805
    2 Southern Cancer Center - Mobile Mobile Alabama United States 36608
    3 Ironwood Cancer TX & Rsch Ctrs Chandler Arizona United States 85224
    4 Arizona Oncology Associates, PC - HAL Tempe Arizona United States 85284
    5 Arizona Oncology Associates, PC - HOPE Tucson Arizona United States 85704
    6 Highlands Oncology Group Fayetteville Arkansas United States 72703
    7 Rocky Mountain Cancer Center - Aurora Aurora Colorado United States 80012
    8 Cancer Care and Hematology Fort Collins Colorado United States 80528
    9 Piedmont Cancer Institute, PC Atlanta Georgia United States 30318
    10 Northwest Georgia Oncology Centers PC - Marietta Marietta Georgia United States 30060
    11 Cancer Care & Hematology; Specialists of Chicagoland Niles Illinois United States 60714
    12 Fort Wayne Med Oncology & Hematology Inc Fort Wayne Indiana United States 46845
    13 Center For Cancer and Blood Disorders Bethesda Maryland United States 20817
    14 Regional Cancer Care Associates LLC - Morristown Morristown New Jersey United States 07962
    15 San Juan Oncology Associates Farmington New Mexico United States 87401
    16 Stony Brook University Hospital Stony Brook New York United States 11794
    17 Northwest Cancer Specialists - Portland (N Broadway) Portland Oregon United States 97227
    18 Oregon Health and Science University Portland Oregon United States 97239
    19 Willamette Valley Cancer Insitute and Research Center Springfield Oregon United States 97477
    20 Texas Oncology-Arlington Arlington Texas United States 76012
    21 Texas Oncology-Tyler Irving Texas United States 75063
    22 Joe Arrington Cancer Research & Treatment Center Lubbock Texas United States 79410
    23 Cancer Care Centers of South Texas-HOAST - San Antonio New Braunfels Texas United States 78130
    24 Northern Utah Associates Ogden Utah United States 84403
    25 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    26 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States 98902

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT02320487
    Other Study ID Numbers:
    • ML29538
    First Posted:
    Dec 19, 2014
    Last Update Posted:
    Feb 11, 2020
    Last Verified:
    Feb 1, 2020
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Bendamustine Hydrochloride
    Obinutuzumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Period Title: Overall Study
    STARTED 102
    COMPLETED 81
    NOT COMPLETED 21

    Baseline Characteristics

    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Overall Participants 102
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.5
    (10.79)
    Sex: Female, Male (Count of Participants)
    Female
    32
    31.4%
    Male
    70
    68.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    1%
    Not Hispanic or Latino
    97
    95.1%
    Unknown or Not Reported
    4
    3.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    2%
    White
    98
    96.1%
    More than one race
    0
    0%
    Unknown or Not Reported
    2
    2%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Complete Response (CR), as Determined by the Investigator Using International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) Guidelines
    Description The CR rate was defined as CR or CR with incomplete blood count recovery (CRi), assessed by the investigator according to iwCLL NCI-WG criteria. The definition of confirmed CR required all of the following criteria as assessed at least 2 months after completion of therapy: peripheral blood lymphocytes < 4 times 10^9 cells/L; absence of significant lymphadenopathy, hepatomegaly, or splenomegaly due to CLL involvement; absence of constitutional symptoms; normal complete blood count (CBC) without need for transfusion or exogenous growth factors, as exhibited by neutrophils >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L, and hemoglobin > 11.0 g/dL; normocellular BM aspirate with < 30% lymphocytes; absence of lymphoid nodules; and BM biopsy without CLL activity. Those fulfilling CR criteria but who have persistent anemia, thrombocytopenia, or neutropenia were considered CRi.
    Time Frame 2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)

    Outcome Measure Data

    Analysis Population Description
    The modified intent-to-treat (mITT) population included enrolled participants who received at least one dose of BG.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Number (95% Confidence Interval) [percentage of participants]
    50.0
    49%
    2. Secondary Outcome
    Title Percentage of Participants With Objective Response of CR or Partial Response (PR) at the End of Induction Therapy, as Determined by the Investigator Using iwCLL NCI-WG Guidelines
    Description CR is defined in the previous outcome measure. The definition of PR required that the following be documented for minimum 2 months: >/= 50% decrease in peripheral blood lymphocytes from Baseline; reduction in lymphadenopathy; >/= 50% reduction in spleen or liver enlargement; and CBC with one of the following without need for transfusion or exogenous growth factors: polymorphonuclear leukocytes >/= 1.5 times 10^9 cells/L, platelets > 100 times 10^9 cells/L or >/= 50% improvement from Baseline, or hemoglobin > 11.0 g/dL or >/= 50% improvement from Baseline.
    Time Frame 2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Number (95% Confidence Interval) [percentage of participants]
    89.2
    87.5%
    3. Secondary Outcome
    Title Duration of Response Among Participants With Objective Response of CR or PR, as Determined by the Investigator Using iwCLL NCI-WG Guidelines
    Description Duration of response was defined as the time from the first assessment of CR, CRi, PR, or nodular partial response (nPR) to the first documentation of PD or death, whichever occurred first. CR, CRi, and PR are identified in previous outcome measures. Participants with lymphoid nodules who otherwise met CR criteria were considered nPR. Participants with post-baseline response assessments (excluding progressive disease) but with no end-of-induction treatment response available were censored on Day 1, and those with end-of-induction treatment response available but who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.
    Time Frame From the first assessment of CR, CRi, PR, or nPR (at up to approximately 228 to 258 days) until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG. Analysis performed for participants with response.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 91
    Median (95% Confidence Interval) [months]
    NA
    4. Secondary Outcome
    Title Progression-Free Survival (PFS), as Determined by the Investigator Using iwCLL NCI-WG Guidelines
    Description PFS was defined as the time from the start of induction treatment (Day 1) to the first occurrence of disease progression, relapse as determined by the investigator using iwCLL NCI WG guidelines, or death (within 28 days after the last dose of study drug), whichever occurred first. Disease progression: at least one of the following: lymphadenopathy; increase in the liver or spleen size by 50% or more or the appearance of hepatomegaly or splenomegaly; an increase in the number of blood lymphocytes by 50% or more with at least 5000 B lymphocytes per microliter; transformation to a more aggressive histology; occurrence of cytopenia (neutropenia, anemia, or thrombocytopenia) attributable to CLL. Relapse: Having achieved CR or PR, but after a period of 6 or more months, having demonstrated evidence of disease progression. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.
    Time Frame Day 1 until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Median (95% Confidence Interval) [months]
    NA
    5. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from the start of induction treatment to death from any cause. Participants who did not experience death or disease progression before the end of the study were censored on the day of the last available assessment.
    Time Frame Day 1 until death from any cause (up to 46 months)

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Median (95% Confidence Interval) [months]
    NA
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved Minimal Residual Disease (MRD)-Negative Status in Bone Marrow at Any Time During the Study
    Description MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in bone marrow aspirate. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.
    Time Frame Up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG. Data are reported for evaluable participants.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 51
    Number (95% Confidence Interval) [percentage of participants]
    58.8
    57.6%
    7. Secondary Outcome
    Title Percentage of Participants Who Achieved MRD-Negative Status in Peripheral Blood at Any Time During the Study
    Description MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture.
    Time Frame Baseline up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG. Data are reported for evaluable participants.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 95
    Number (95% Confidence Interval) [percentage of participants]
    83.2
    81.6%
    8. Secondary Outcome
    Title Time to MRD-Negative Status in Peripheral Blood
    Description MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity if the value is <10^-4 (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Time to MRD-negative status is defined as the time between MRD positivity (>= 10^-4) or the time of first dose treatment for patients who were missing MRD status assessment at baseline to the first achievement of MRD negativity in the peripheral blood.
    Time Frame Baseline up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Median (95% Confidence Interval) [months]
    8.2
    9. Secondary Outcome
    Title Duration of MRD-Negativity in Peripheral Blood Among Participants Who Achieved MRD-Negative Status
    Description MRD was assessed by 4-color flow cytometry, using iwCLL criteria for MRD negativity (<1 CLL cell detected in 10,000 leukocytes) in peripheral blood. Flow cytometry provides rapid analysis of multiple characteristics of single cells by using light to count and profile cells in a fluid mixture. Duration of MRD-negativity among patients who achieved MRD negativity in the study is defined as the period between the first occurrence of MRD-negative status and a subsequent MRD-positive status.
    Time Frame Baseline up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The mITT population included enrolled participants who received at least one dose of BG. Data are reported for evaluable participants.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 79
    Median (95% Confidence Interval) [months]
    28.9
    10. Secondary Outcome
    Title Minimum Observed Concentration (Ctrough) of Obinutuzumab After Cycle 2
    Description Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.
    Time Frame Pre-infusion (0 hours) on Day 1 Cycle 3 (1 cycle = 28 days)

    Outcome Measure Data

    Analysis Population Description
    The PK (pharmacokinetic) Evaluable Population included all ITT participants in the study who received any dose of study drug (obinutuzumab or bendamustine) and had at least one PK assessment. Data are reported for evaluable participants.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 95
    Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]
    235.92
    (48.01)
    11. Secondary Outcome
    Title Ctrough of Obinutuzumab After Cycle 4
    Description Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state.
    Time Frame Pre-infusion (0 hours) on Day 1 Cycle 5 (1 cycle = 28 days)

    Outcome Measure Data

    Analysis Population Description
    The PK (pharmacokinetic) Evaluable Population included all ITT participants in the study who received any dose of study drug (obinutuzumab or bendamustine) and had at least one PK assessment. Data are reported for evaluable participants.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 80
    Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]
    264.27
    (46.45)
    12. Secondary Outcome
    Title Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
    Description The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.
    Time Frame Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)

    Outcome Measure Data

    Analysis Population Description
    The PRO (patient-reported outcome) Evaluable Population included all ITT participants in the study who received any dose of study treatment (obinutuzumab or bendamustine) and had both a non-missing baseline and at least one post-baseline PRO assessment. Data were not collected for the second year of follow up.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 98
    Global Health Status (GHS)/QoL: Cycle 3
    4.02
    (21.540)
    GHS/QoL: Cycle 6
    5.26
    (22.478)
    GHS/QoL: EOT/Early Discontinuation
    5.17
    (26.731)
    GHS/QoL: Response Visit
    10.98
    (21.715)
    GHS/QoL: 3-Month Follow-Up
    10.25
    (24.733)
    GHS/QoL: 6-Month Follow-Up
    5.68
    (30.140)
    GHS/QoL: 9-Month Follow-Up
    9.26
    (23.384)
    GHS/QoL: 12-Month Follow-Up
    6.43
    (24.676)
    GHS/QoL: 15-Month Follow-Up
    6.57
    (25.969)
    GHS/QoL: 18-Month Follow-Up
    9.84
    (26.732)
    GHS/QoL: 21-Month Follow-Up
    7.60
    (27.117)
    GHS/QoL: 24-Month Follow-Up
    8.91
    (27.388)
    GHS/QoL: 27-Month Follow-Up
    13.26
    (24.468)
    GHS/QoL: 30-Month Follow-Up
    1.66
    (28.501)
    Physical Function: Cycle 3
    -2.46
    (14.948)
    Physical Function: Cycle 6
    0.00
    (12.842)
    Phys. Function: EOT/Early Discontinuation
    2.62
    (15.188)
    Physical Function: Response Visit
    3.90
    (14.705)
    Physical Function: 3-Month Follow-Up
    4.14
    (13.769)
    Physical Function: 6-Month Follow-Up
    1.62
    (17.308)
    Physical Function: 9-Month Follow-Up
    4.95
    (15.208)
    Physical Function: 12-Month Follow-Up
    3.00
    (15.221)
    Physical Function: 15-Month Follow-Up
    2.44
    (17.647)
    Physical Function: 18-Month Follow-Up
    1.11
    (18.589)
    Physical Function: 21-Month Follow-Up
    1.37
    (13.509)
    Physical Function: 24-Month Follow-Up
    3.10
    (14.467)
    Physical Function: 27-Month Follow-Up
    4.22
    (14.057)
    Physical Function: 30-Month Follow-Up
    5.34
    (8.691)
    Role Function: Cycle 3
    6.01
    (24.775)
    Role Function: Cycle 6
    4.11
    (27.193)
    Role Function: EOT/Early Discontinuation
    10.55
    (27.108)
    Role Function: Response Visit
    13.14
    (29.106)
    Role Function: 3-Month Follow-Up
    14.87
    (28.210)
    Role Function: 6-Month Follow-Up
    10.86
    (29.453)
    Role Function: 9-Month Follow-Up
    15.51
    (27.312)
    Role Function: 12-Month Follow-Up
    10.63
    (28.591)
    Role Function: 15-Month Follow-Up
    12.68
    (30.920)
    Role Function: 18-Month Follow-Up
    10.88
    (33.352)
    Role Function: 21-Month Follow-Up
    10.95
    (28.656)
    Role Function: 24-Month Follow-Up
    11.49
    (30.780)
    Role Function: 27-Month Follow-Up
    14.97
    (30.285)
    Role Function: 30-Month Follow-Up
    -13.33
    (36.132)
    Emotional Function: Cycle 3
    7.91
    (18.092)
    Emotional Function: Cycle 6
    6.29
    (18.304)
    Emotional Function: EOT/Early Discont.
    9.60
    (18.302)
    Emotional Function: Response Visit
    9.12
    (18.663)
    Emotional Function: 3-Month Follow-Up
    8.11
    (18.861)
    Emotional Function: 6-Month Follow-Up
    6.94
    (19.424)
    Emotional Function: 9-Month Follow-Up
    11.00
    (13.402)
    Emotional Function: 12-Month Follow-Up
    7.81
    (18.793)
    Emotional Function: 15-Month Follow-Up
    6.34
    (23.883)
    Emotional Function: 18-Month Follow-Up
    5.75
    (22.214)
    Emotional Function: 21-Month Follow-Up
    7.11
    (19.597)
    Emotional Function: 24-Month Follow-Up
    9.77
    (19.380)
    Emotional Function: 27-Month Follow-Up
    10.15
    (18.845)
    Emotional Function: 30-Month Follow-Up
    8.33
    (15.591)
    Cognitive Function: Cycle 3
    2.55
    (22.640)
    Cognitive Function: Cycle 6
    -1.75
    (25.177)
    Cognitive Function: EOT/Early Discont.
    0.42
    (17.697)
    Cognitive Function: Response Visit
    2.74
    (20.387)
    Cognitive Function: 3-Month Follow-Up
    2.25
    (17.946)
    Cognitive Function: 6-Month Follow-Up
    1.77
    (23.043)
    Cognitive Function: 9-Month Follow-Up
    6.02
    (17.312)
    Cognitive Function: 12-Month Follow-Up
    1.48
    (19.646)
    Cognitive Function: 15-Month Follow-Up
    2.11
    (20.878)
    Cognitive Function: 18-Month Follow-Up
    2.55
    (20.105)
    Cognitive Function: 21-Month Follow-Up
    3.19
    (20.815)
    Cognitive Function: 24-Month Follow-Up
    4.02
    (18.550)
    Cognitive Function: 27-Month Follow-Up
    1.70
    (16.401)
    Cognitive Function: 30-Month Follow-Up
    -3.33
    (21.726)
    Social Function: Cycle 3
    -2.35
    (21.386)
    Social Function: Cycle 6
    -4.17
    (23.590)
    Social Function: EOT/Early Discontinuation
    2.53
    (23.279)
    Social Function: Response Visit
    5.69
    (24.874)
    Social Function: 3-Month Follow-Up
    5.41
    (23.587)
    Social Function: 6-Month Follow-Up
    -0.25
    (26.872)
    Social Function: 9-Month Follow-Up
    8.10
    (19.579)
    Social Function: 12-Month Follow-Up
    2.74
    (24.667)
    Social Function: 15-Month Follow-Up
    3.76
    (25.696)
    Social Function: 18-Month Follow-Up
    3.70
    (27.296)
    Social Function: 21-Month Follow-Up
    2.70
    (26.952)
    Social Function: 24-Month Follow-Up
    5.46
    (21.032)
    Social Function: 27-Month Follow-Up
    7.48
    (23.088)
    Social Function: 30-Month Follow-Up
    -10.00
    (30.277)
    Fatigue: Cycle 3
    -4.01
    (25.433)
    Fatigue: Cycle 6
    -5.48
    (24.558)
    Fatigue: EOT/Early Discontinuation
    -11.67
    (24.324)
    Fatigue: Response Visit
    -16.34
    (25.291)
    Fatigue: 3-Month Follow-Up
    -15.92
    (24.266)
    Fatigue: 6-Month Follow-Up
    -13.64
    (24.171)
    Fatigue: 9-Month Follow-Up
    -17.28
    (23.947)
    Fatigue: 12-Month Follow-Up
    -13.12
    (24.261)
    Fatigue: 15-Month Follow-Up
    -11.27
    (25.441)
    Fatigue: 18-Month Follow-Up
    -13.43
    (24.946)
    Fatigue: 21-Month Follow-Up
    -13.07
    (22.465)
    Fatigue: 24-Month Follow-Up
    -14.37
    (21.429)
    Fatigue: 27-Month Follow-Up
    -14.51
    (23.373)
    Fatigue: 30-Month Follow-Up
    -2.22
    (16.480)
    Nausea/Vomiting: Cycle 3
    2.33
    (16.990)
    Nausea/Vomiting: Cycle 6
    3.68
    (14.210)
    Nausea/Vomiting: EOT/Early Discontinuation
    2.32
    (13.273)
    Nausea/Vomiting: Response Visit
    -0.39
    (15.209)
    Nausea/Vomiting: 3-Month Follow-Up
    -1.58
    (9.624)
    Nausea/Vomiting: 6-Month Follow-Up
    -1.26
    (12.164)
    Nausea/Vomiting: 9-Month Follow-Up
    -0.23
    (16.428)
    Nausea/Vomiting: 12-Month Follow-Up
    -1.04
    (13.350)
    Nausea/Vomiting: 15-Month Follow-Up
    0.70
    (13.926)
    Nausea/Vomiting: 18-Month Follow-Up
    -0.23
    (13.267)
    Nausea/Vomiting: 21-Month Follow-Up
    -1.72
    (13.240)
    Nausea/Vomiting: 24-Month Follow-Up
    -2.01
    (14.333)
    Nausea/Vomiting: 27-Month Follow-Up
    -1.70
    (14.925)
    Nausea/Vomiting: 30-Month Follow-Up
    10.00
    (14.910)
    Pain: Cycle 3
    -3.68
    (17.969)
    Pain: Cycle 6
    0.65
    (26.826)
    Pain: EOT/Early Discontinuation
    -1.90
    (21.012)
    Pain: Response Visit
    -4.90
    (20.865)
    Pain: 3-Month Follow-Up
    -1.80
    (17.570)
    Pain: 6-Month Follow-Up
    -1.52
    (20.615)
    Pain: 9-Month Follow-Up
    -0.69
    (20.448)
    Pain: 12-Month Follow-Up
    -0.21
    (24.947)
    Pain: 15-Month Follow-Up
    0.94
    (26.709)
    Pain: 18-Month Follow-Up
    -0.46
    (25.326)
    Pain: 21-Month Follow-Up
    -0.00
    (23.035)
    Pain: 24-Month Follow-Up
    -2.59
    (19.447)
    Pain: 27-Month Follow-Up
    -5.44
    (26.654)
    Pain: 30-Month Follow-Up
    6.67
    (48.015)
    Dyspnoea: Cycle 3
    0.39
    (27.294)
    Dyspnoea: Cycle 6
    -1.73
    (25.874)
    Dyspnoea: EOT/Early Discontinuation
    -5.91
    (31.013)
    Dyspnoea: Response Visit
    -5.88
    (30.069)
    Dyspnoea: 3-Month Follow-Up
    -9.46
    (27.872)
    Dyspnoea: 6-Month Follow-Up
    -8.08
    (27.463)
    Dyspnoea: 9-Month Follow-Up
    -7.87
    (29.334)
    Dyspnoea: 12-Month Follow-Up
    -5.83
    (30.824)
    Dyspnoea: 15-Month Follow-Up
    -5.63
    (29.270)
    Dyspnoea: 18-Month Follow-Up
    -7.87
    (28.796)
    Dyspnoea: 21-Month Follow-Up
    -8.82
    (27.289)
    Dyspnoea: 24-Month Follow-Up
    -7.47
    (28.642)
    Dyspnoea: 27-Month Follow-Up
    -11.56
    (31.587)
    Dyspnoea: 30-Month Follow-Up
    -20.00
    (18.256)
    Insomnia: Cycle 3
    -6.59
    (27.450)
    Insomnia: Cycle 6
    -9.09
    (24.565)
    Insomnia: EOT/Early Discontinuation
    -9.70
    (25.684)
    Insomnia: Response Visit
    -10.98
    (28.354)
    Insomnia: 3-Month Follow-Up
    -9.46
    (25.596)
    Insomnia: 6-Month Follow-Up
    -14.65
    (29.312)
    Insomnia: 9-Month Follow-Up
    -12.50
    (29.306)
    Insomnia: 12-Month Follow-Up
    -9.70
    (31.193)
    Insomnia: 15-Month Follow-Up
    -13.61
    (30.643)
    Insomnia: 18-Month Follow-Up
    -8.80
    (30.640)
    Insomnia: 21-Month Follow-Up
    -7.84
    (29.991)
    Insomnia: 24-Month Follow-Up
    -14.37
    (28.691)
    Insomnia: 27-Month Follow-Up
    -10.20
    (36.136)
    Insomnia: 30-Month Follow-Up
    -6.67
    (49.443)
    Appetite Loss: Cycle 3
    -2.71
    (20.589)
    Appetite Loss: Cycle 6
    0.00
    (26.490)
    Appetite Loss: EOT/Early Discontinuation
    -3.80
    (18.480)
    Appetite Loss: Response Visit
    -7.06
    (21.878)
    Appetite Loss: 3-Month Follow-Up
    -9.91
    (18.896)
    Appetite Loss: 6-Month Follow-Up
    -9.60
    (18.270)
    Appetite Loss: 9-Month Follow-Up
    -10.80
    (22.378)
    Appetite Loss: 12-Month Follow-Up
    -8.75
    (20.364)
    Appetite Loss: 15-Month Follow-Up
    -6.57
    (24.312)
    Appetite Loss: 18-Month Follow-Up
    -7.41
    (19.557)
    Appetite Loss: 21-Month Follow-Up
    -4.90
    (23.928)
    Appetite Loss: 24-Month Follow-Up
    -7.47
    (20.748)
    Appetite Loss: 27-Month Follow-Up
    -8.16
    (19.872)
    Appetite Loss: 30-Month Follow-Up
    -6.67
    (14.906)
    Constipation: Cycle 3
    3.92
    (34.661)
    Constipation: Cycle 6
    -0.00
    (24.944)
    Constipation: EOT/Early Discontinuation
    -4.27
    (18.105)
    Constipation: Response Visit
    -4.36
    (24.147)
    Constipation: 3-Month Follow-Up
    -5.02
    (18.979)
    Constipation: 6-Month Follow-Up
    -6.06
    (19.312)
    Constipation: 9-Month Follow-Up
    -5.16
    (24.975)
    Constipation: 12-Month Follow-Up
    -3.80
    (25.028)
    Constipation: 15-Month Follow-Up
    -3.76
    (19.147)
    Constipation: 18-Month Follow-Up
    -0.46
    (24.059)
    Constipation: 21-Month Follow-Up
    -2.45
    (22.538)
    Constipation: 24-Month Follow-Up
    -6.32
    (21.134)
    Constipation: 27-Month Follow-Up
    -6.80
    (21.494)
    Constipation: 30-Month Follow-Up
    0.00
    (0.000)
    Diarrhoea: Cycle 3
    1.18
    (21.483)
    Diarrhoea: Cycle 6
    4.82
    (24.767)
    Diarrhoea: EOT/Early Discontinuation
    4.64
    (29.105)
    Diarrhoea: Response Visit
    2.75
    (24.780)
    Diarrhoea: 3-Month Follow-Up
    -2.25
    (20.886)
    Diarrhoea: 6-Month Follow-Up
    -1.01
    (24.085)
    Diarrhoea: 9-Month Follow-Up
    3.24
    (23.174)
    Diarrhoea: 12-Month Follow-Up
    -0.43
    (21.816)
    Diarrhoea: 15-Month Follow-Up
    0.00
    (25.197)
    Diarrhoea: 18-Month Follow-Up
    -2.78
    (26.090)
    Diarrhoea: 21-Month Follow-Up
    3.43
    (28.875)
    Diarrhoea: 24-Month Follow-Up
    -0.57
    (22.067)
    Diarrhoea: 27-Month Follow-Up
    1.36
    (21.471)
    Diarrhoea: 30-Month Follow-Up
    0.00
    (23.568)
    Financial Difficulty: Cycle 3
    0.78
    (25.186)
    Financial Difficulty: Cycle 6
    -2.19
    (27.934)
    Financial Difficulty: EOT/Early Discont.
    -1.27
    (26.923)
    Financial Difficulty: Response Visit
    -3.53
    (29.107)
    Financial Difficulty: 3-Month Follow-Up
    -5.86
    (27.784)
    Financial Difficulty: 6-Month Follow-Up
    -7.18
    (27.947)
    Financial Difficulty: 9-Month Follow-Up
    -7.04
    (26.972)
    Financial Difficulty: 12-Month Follow-Up
    -3.80
    (30.188)
    Financial Difficulty: 15-Month Follow-Up
    -8.45
    (29.125)
    Financial Difficulty: 18-Month Follow-Up
    -6.02
    (31.313)
    Financial Difficulty: 21-Month Follow-Up
    -6.86
    (25.471)
    Financial Difficulty: 24-Month Follow-Up
    -7.47
    (26.523)
    Financial Difficulty: 27-Month Follow-Up
    -11.56
    (31.587)
    Financial Difficulty: 30-Month Follow-Up
    -13.33
    (29.813)
    13. Secondary Outcome
    Title Change From Baseline in the EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) Score
    Description The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) module included assessments of fatigue, treatment side effects, disease symptoms, infection, social activities, and future health worries. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive change from Day 1, Cycle 1 (baseline) indicates improvement. EOT=end of treatment.
    Time Frame Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)

    Outcome Measure Data

    Analysis Population Description
    The PRO Evaluable Population included all ITT participants in the study who received any dose of study treatment (obinutuzumab or bendamustine) and had both a non-missing baseline and at least one post-baseline PRO assessment. Data were not collected for the second year of follow up.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 98
    Fatigue: Cycle 3
    -12.02
    (26.892)
    Fatigue: Cycle 6
    -10.17
    (26.373)
    Fatigue: EOT/Early Discontinuation
    -12.87
    (30.306)
    Fatigue: Response Visit
    -21.23
    (30.759)
    Fatigue: 3-Month Follow-Up
    -20.04
    (29.323)
    Fatigue: 6-Month Follow-Up
    -17.44
    (25.418)
    Fatigue: 9-Month Follow-Up
    -22.77
    (27.780)
    Fatigue: 12-Month Follow-Up
    -17.32
    (25.569)
    Fatigue: 15-Month Follow-Up
    -14.52
    (30.153)
    Fatigue: 18-Month Follow-Up
    -15.49
    (30.122)
    Fatigue: 21-Month Follow-Up
    -16.42
    (28.646)
    Fatigue: 24-Month Follow-Up
    -24.70
    (25.621)
    Fatigue: 27-Month Follow-Up
    -19.56
    (26.597)
    Fatigue: 30-Month Follow-Up
    -6.67
    (53.489)
    Side Effects: Cycle 3
    1.52
    (12.019)
    Side Effects: Cycle 6
    0.07
    (16.072)
    Side Effects: EOT/Early Discontinuation
    -0.67
    (16.357)
    Side Effects: Response Visit
    -2.08
    (14.520)
    Side Effects: 3-Month Follow-Up
    -3.30
    (12.904)
    Side Effects: 6-Month Follow-Up
    -2.61
    (15.182)
    Side Effects: 9-Month Follow-Up
    -3.36
    (14.548)
    Side Effects: 12-Month Follow-Up
    -2.27
    (14.841)
    Side Effects: 15-Month Follow-Up
    -3.17
    (14.355)
    Side Effects: 18-Month Follow-Up
    -4.54
    (14.813)
    Side Effects: 21-Month Follow-Up
    -1.66
    (16.277)
    Side Effects: 24-Month Follow-Up
    -3.08
    (13.699)
    Side Effects: 27-Month Follow-Up
    -2.96
    (14.434)
    Side Effects: 30-Month Follow-Up
    -11.67
    (4.566)
    Disease Symptoms: Cycle 3
    -9.56
    (18.196)
    Disease Symptoms: Cycle 6
    -8.30
    (20.039)
    Disease Symptoms: EOT/Early Discontinuation
    -10.02
    (20.371)
    Disease Symptoms: Response Visit
    -12.67
    (18.019)
    Disease Symptoms: 3-Month Follow-Up
    -12.20
    (18.630)
    Disease Symptoms: 6-Month Follow-Up
    -10.13
    (16.699)
    Disease Symptoms: 9-Month Follow-Up
    -12.28
    (18.478)
    Disease Symptoms: 12-Month Follow-Up
    -8.62
    (18.297)
    Disease Symptoms: 15-Month Follow-Up
    -9.05
    (19.284)
    Disease Symptoms: 18-Month Follow-Up
    -10.41
    (20.632)
    Disease Symptoms: 21-Month Follow-Up
    -9.16
    (21.398)
    Disease Symptoms: 24-Month Follow-Up
    -10.71
    (17.675)
    Disease Symptoms: 27-Month Follow-Up
    -11.41
    (19.904)
    Disease Symptoms: 30-Month Follow-Up
    -5.00
    (20.917)
    Infection: Cycle 3
    6.20
    (18.182)
    Infection: Cycle 6
    4.11
    (16.406)
    Infection: EOT/Early Discontinuation
    1.65
    (15.199)
    Infection: Response Visit
    0.76
    (17.528)
    Infection: 3-Month Follow-Up
    2.59
    (20.779)
    Infection: 6-Month Follow-Up
    3.46
    (23.611)
    Infection: 9-Month Follow-Up
    1.45
    (17.135)
    Infection: 12-Month Follow-Up
    4.42
    (22.269)
    Infection: 15-Month Follow-Up
    2.86
    (19.602)
    Infection: 18-Month Follow-Up
    2.62
    (22.532)
    Infection: 21-Month Follow-Up
    2.78
    (18.502)
    Infection: 24-Month Follow-Up
    0.89
    (15.134)
    Infection: 27-Month Follow-Up
    1.45
    (14.731)
    Infection: 30-Month Follow-Up
    -5.00
    (9.502)
    Social Activities: Cycle 3
    -3.92
    (28.827)
    Social Activities: Cycle 6
    -3.95
    (34.412)
    Social Activities: EOT/Early Discont.
    -6.41
    (33.141)
    Social Activities: Response Visit
    -9.24
    (33.054)
    Social Activities: 3-Month Follow-Up
    -11.87
    (27.983)
    Social Activities: 6-Month Follow-Up
    -4.69
    (33.527)
    Social Activities: 9-Month Follow-Up
    -13.33
    (28.033)
    Social Activities: 12-Month Follow-Up
    -7.89
    (27.145)
    Social Activities: 15-Month Follow-Up
    -6.76
    (34.099)
    Social Activities: 18-Month Follow-Up
    -5.71
    (31.583)
    Social Activities: 21-Month Follow-Up
    -4.55
    (32.495)
    Social Activities: 24-Month Follow-Up
    -11.51
    (28.845)
    Social Activities: 27-Month Follow-Up
    -9.42
    (29.534)
    Social Activities: 30-Month Follow-Up
    0.00
    (66.668)
    Future Health Worries: Cycle 3
    -20.08
    (30.329)
    Future Health Worries: Cycle 6
    -14.04
    (29.946)
    Future Health Worries: EOT/Early Discont.
    -18.57
    (32.794)
    Future Health Worries: Response Visit
    -20.24
    (28.351)
    Future Health Worries: 3-Month Follow-Up
    -25.11
    (29.805)
    Future Health Worries: 6-Month Follow-Up
    -17.44
    (30.680)
    Future Health Worries: 9-Month Follow-Up
    -23.47
    (27.253)
    Future Health Worries: 12-Month Follow-Up
    -19.23
    (26.053)
    Future Health Worries: 15-Month Follow-Up
    -17.14
    (33.929)
    Future Health Worries: 18-Month Follow-Up
    -19.72
    (34.540)
    Future Health Worries: 21-Month Follow-Up
    -21.21
    (27.820)
    Future Health Worries: 24-Month Follow-Up
    -21.82
    (30.911)
    Future Health Worries: 27-Month Follow-Up
    -25.36
    (31.572)
    Future Health Worries: 30-Month Follow-Up
    -6.67
    (27.892)
    14. Secondary Outcome
    Title Number of Hospitalizations Due to Adverse Events (AEs)
    Description An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.
    Time Frame Day 1 up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The safety population included participants who received any amount of study treatment.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Mean (Standard Deviation) [hospitalizations]
    1.43
    (0.634)
    15. Secondary Outcome
    Title Percentage of Participants With Adverse Events (AEs)
    Description An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.
    Time Frame Day 1 up to 46 months

    Outcome Measure Data

    Analysis Population Description
    The safety population included participants who received any amount of study treatment.
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    Measure Participants 102
    Number [percentage of participants]
    100
    98%

    Adverse Events

    Time Frame Day 1 up to 46 months
    Adverse Event Reporting Description
    Arm/Group Title Obinutuzumab + Bendamustine (BG)
    Arm/Group Description Participants received obinutuzumab + bendamustine (BG) therapy in 28-day cycles for 6 cycles.
    All Cause Mortality
    Obinutuzumab + Bendamustine (BG)
    Affected / at Risk (%) # Events
    Total 7/102 (6.9%)
    Serious Adverse Events
    Obinutuzumab + Bendamustine (BG)
    Affected / at Risk (%) # Events
    Total 31/102 (30.4%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/102 (3.9%) 4
    Anaemia 1/102 (1%) 1
    Cardiac disorders
    Cardiac arrest 1/102 (1%) 1
    Myocardial infarction 1/102 (1%) 1
    Cardiac failure congestive 1/102 (1%) 1
    Gastrointestinal disorders
    Vomiting 1/102 (1%) 1
    General disorders
    Pyrexia 5/102 (4.9%) 5
    Infections and infestations
    Pneumonia 7/102 (6.9%) 8
    Urinary tract infection 2/102 (2%) 2
    Catheter site infection 1/102 (1%) 1
    Infection 1/102 (1%) 1
    Oesophageal candidiasis 1/102 (1%) 1
    Septic shock 1/102 (1%) 1
    Progressive multifocal leukoencephalopathy 1/102 (1%) 1
    Sepsis 1/102 (1%) 1
    Injury, poisoning and procedural complications
    Infusion related reaction 2/102 (2%) 2
    Investigations
    Blood creatinine increased 1/102 (1%) 1
    Metabolism and nutrition disorders
    Dehydration 3/102 (2.9%) 3
    Tumour lysis syndrome 4/102 (3.9%) 4
    Failure to thrive 1/102 (1%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/102 (1%) 1
    Vascular disorders
    Hypotension 2/102 (2%) 2
    Other (Not Including Serious) Adverse Events
    Obinutuzumab + Bendamustine (BG)
    Affected / at Risk (%) # Events
    Total 101/102 (99%)
    Blood and lymphatic system disorders
    Neutropenia 36/102 (35.3%) 53
    Thrombocytopenia 20/102 (19.6%) 42
    Anaemia 14/102 (13.7%) 18
    Gastrointestinal disorders
    Nausea 54/102 (52.9%) 74
    Constipation 27/102 (26.5%) 29
    Diarrhoea 24/102 (23.5%) 34
    Vomiting 21/102 (20.6%) 33
    Abdominal pain 11/102 (10.8%) 13
    Dyspepsia 7/102 (6.9%) 7
    General disorders
    Fatigue 36/102 (35.3%) 48
    Pyrexia 35/102 (34.3%) 44
    Oedema peripheral 16/102 (15.7%) 16
    Chills 13/102 (12.7%) 13
    Infections and infestations
    Upper respiratory tract infection 14/102 (13.7%) 15
    Bronchitis 6/102 (5.9%) 6
    Pneumonia 6/102 (5.9%) 6
    Injury, poisoning and procedural complications
    Infusion related reaction 76/102 (74.5%) 96
    Investigations
    Neutrophil count decreased 15/102 (14.7%) 24
    Platelet count decreased 8/102 (7.8%) 15
    Weight decreased 8/102 (7.8%) 10
    Metabolism and nutrition disorders
    Dehydration 15/102 (14.7%) 18
    Decreased appetite 12/102 (11.8%) 13
    Hypokalaemia 9/102 (8.8%) 14
    Hypomagnesaemia 6/102 (5.9%) 7
    Hyponatraemia 6/102 (5.9%) 6
    Musculoskeletal and connective tissue disorders
    Arthralgia 13/102 (12.7%) 16
    Bone pain 8/102 (7.8%) 8
    Pain in extremity 9/102 (8.8%) 10
    Back pain 7/102 (6.9%) 7
    Muscle spasms 7/102 (6.9%) 7
    Myalgia 7/102 (6.9%) 8
    Nervous system disorders
    Headache 19/102 (18.6%) 24
    Dizziness 12/102 (11.8%) 16
    Dysgeusia 8/102 (7.8%) 8
    Psychiatric disorders
    Insomnia 19/102 (18.6%) 20
    Anxiety 7/102 (6.9%) 7
    Respiratory, thoracic and mediastinal disorders
    Cough 17/102 (16.7%) 21
    Dyspnoea 8/102 (7.8%) 8
    Dyspnoea exertional 6/102 (5.9%) 8
    Skin and subcutaneous tissue disorders
    Rash 28/102 (27.5%) 42
    Dry skin 10/102 (9.8%) 10
    Pruritus 7/102 (6.9%) 10
    Night sweats 6/102 (5.9%) 6
    Vascular disorders
    Flushing 7/102 (6.9%) 9
    Hypotension 8/102 (7.8%) 8

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-LaRoche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT02320487
    Other Study ID Numbers:
    • ML29538
    First Posted:
    Dec 19, 2014
    Last Update Posted:
    Feb 11, 2020
    Last Verified:
    Feb 1, 2020