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A Study Comparing Obinutuzumab (RO5072759; GA101) 1000 Milligram (mg) Versus 2000 mg in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GAGE)

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ClinicalTrials.gov Identifier: NCT01414205
Recruitment Status : Completed
First Posted : August 11, 2011
Results First Posted : April 24, 2014
Last Update Posted : April 17, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphocytic Leukemia, Chronic
Interventions Drug: Obinutuzumab
Drug: Corticosteroids
Enrollment 80
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose. Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Period Title: Overall Study
Started 41 39
Received Study Drug 40 38
Completed 34 32
Not Completed 7 7
Reason Not Completed
Death             5             1
Lost to Follow-up             1             4
Physician Decision             0             1
Randomized but not Treated             1             1
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg Total
Hide Arm/Group Description Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose. Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose. Total of all reporting groups
Overall Number of Baseline Participants 41 39 80
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 39 participants 80 participants
67.0  (10.0) 64.3  (12.4) 65.7  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
Female
16
  39.0%
13
  33.3%
29
  36.3%
Male
25
  61.0%
26
  66.7%
51
  63.7%
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the percentage of participants with complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR) as assessed by the investigator according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines two months after last treatment. CR required: blood lymphocytes < 4 x 10^9/Liter (L), absence of lymphadenopathy (≤ 1.5 centimeter (cm) in long axis by Computed Tomography), no hepatomegaly or splenomegaly, absence of disease, Neutrophils > 1.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin >11 g/dL, bone marrow normal and lymphoid nodules absent. CRi was CR with incomplete marrow recovery. PR required: 50% decrease in peripheral blood lymphocyte count, 50% reduction in lymphadenopathy, 50% reduction of liver and/or spleen enlargement if enlarged at baseline, Neutrophils > 1.5 x 10^9/L or > 50% of pretreatment value, Platelets > 100 x 10^9/L or 50% of pretreatment value and Hemoglobin > 11 g/dL or > 50% of pretreatment value.
Time Frame Week 32
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Hide Analysis Population Description
Intent-to-treat population included all randomized participants.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Percentage of participants
48.8 66.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obinutuzumab 1000 mg, Obinutuzumab 2000 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0779
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments P-values based on stratified Cochran-Mantel-Haenszel test by the randomization stratification factors as supportive analyses.
Method of Estimation Estimation Parameter Difference (Hauck-Anderson)
Estimated Value 17.89
Confidence Interval (2-Sided) 95%
-4.95 to 40.72
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the time from the randomization to the first occurrence of progression or death, whichever occurred first.
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 41 39
Median (95% Confidence Interval)
Unit of Measure: Months
25.2
(15.9 to 30.4)
26.0
(20.2 to 34.2)
3.Secondary Outcome
Title Duration of Response
Hide Description [Not Specified]
Time Frame Up to 4 years, 5 months
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Number of Participants Surviving at End-of-Study
Hide Description [Not Specified]
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population included all randomized participants.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 41 39
Measure Type: Number
Unit of Measure: Participants
35 37
5.Secondary Outcome
Title Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. A SAE was any AE that was one of the following: fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product or considered a significant medical event by the investigator. Additional information about AEs can be found in the Adverse Event Section.
Time Frame Up to 4 years, 5 months
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Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 40 38
Measure Type: Number
Unit of Measure: Percentage of participants
Adverse Events 100.0 100.0
Serious Adverse Events 20.0 21.1
6.Secondary Outcome
Title Percentage of Participants With Adverse Events of Interest
Hide Description Adverse Events of interest for this study were: serious infusion related reactions during or within 24 hours of infusion, serious neutropenia, serious infection, tumor lysis syndrome and Hepatitis B reactivation.
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 40 38
Measure Type: Number
Unit of Measure: Percentage of participants
Serious Infusion-Related Reactions (IRR) 7.5 5.3
Serious Neutropenia 5.0 5.3
Serious Infection 5.0 5.3
Tumor Lysis Syndrome 0.0 2.6
Hepatitis B Reactivation 0.0 0.0
7.Secondary Outcome
Title Percentage of Participants With Adverse Events Leading to Study Discontinuation
Hide Description An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 40 38
Measure Type: Number
Unit of Measure: Percentage of participants
0 0
8.Secondary Outcome
Title PK Parameter: Maximum Serum Concentration (Cmax)
Hide Description Blood was collected for Pharmacokinetic (PK) Parameter Cmax after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).
Time Frame Day 148 (at end of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 37 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
600
(45.6%)
1190
(34.9%)
9.Secondary Outcome
Title PK Parameter: Area Under the Serum Concentration-Time Curve Between Dosing Interval Tau (AUCt )
Hide Description Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in day times micrograms per milliliter (day*μg/mL).
Time Frame Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*μg/mL
8230
(58.3%)
16500
(50.3%)
10.Secondary Outcome
Title PK Parameter: Clearance at Steady State (CLss)
Hide Description Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). CLss is reported in milliliters per day (mL/day).
Time Frame Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/day
121
(58.3%)
122
(50.3%)
11.Secondary Outcome
Title PK Parameter: Volume of Distribution at Steady State (Vss)
Hide Description Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). Vss is reported in liters.
Time Frame Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 24 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
7.08
(73.2%)
6.68
(74.7%)
12.Secondary Outcome
Title PK Parameter: Terminal Half-Life (t1/2)
Hide Description Blood was collected for PK Parameters before and after dose administration on Day 1 of Cycle 8. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA). T1/2 was reported in Days.
Time Frame Day 148 (pre-infusion, at end of infusion, 5, 8 and 12 days after start of infusion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 24 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Days
30.6
(87.1%)
26.3
(80.1%)
13.Secondary Outcome
Title PK: Serum Concentrations of Obinutuzumab (Follow-Up Visits)
Hide Description Blood serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).
Time Frame Months 3, 6, 9, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received study drug with PK data available for analysis. Participants with insufficient data points for PK estimation were excluded.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 37 33
Mean (Standard Deviation)
Unit of Measure: μg/mL
Month 3 (n=14, 10) 41.2  (63.3) 98.9  (88.9)
Month 6 (n=19, 15) 15  (21.4) 12.6  (17.7)
Month 9 (n=24, 23) 2.63  (4.4) 4.09  (9.42)
Month 12 (n=16, 18) 0.633  (1.11) 0.857  (1.74)
14.Secondary Outcome
Title Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion
Hide Description Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell depletion was defined as a CD19 result < 0.07 × 10^9/L after at least one dose of study drug has been administered.
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Safety Evaluable Population, all randomized participants who received at least one dose of study drug, who had data available for this outcome measure.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 40 38
Measure Type: Number
Unit of Measure: Participants
At Last Antibody Administration (n=40, 38) 31 31
Up to 6 Months of Follow-Up (FU) (n=30, 31) 28 28
Within 6-12 Months of Follow-up (n=24, 24) 16 17
Within 12-18 Months of Follow-up (n=17, 17) 11 9
Within 18-24 Months of Follow-up (n=10, 9) 5 8
Within 24-30 Months of Follow-up (n=4, 6) 2 5
Within 30-36 Months of Follow-up (n=1, 3) 1 3
Within 36-42 Months of Follow-up (n=0, 0) 0 0
After 42 Months of Follow-up (n=0, 0) 0 0
15.Secondary Outcome
Title Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery
Hide Description Blood was sent to a central laboratory for the evaluation of cluster of differentiation 19 (CD19) by flow cytometry. B-cell recovery was defined as a CD19 result ≥ 0.07 × 10^9/L, where CD19 was previously depleted. B-cell recovery was only considered possible following the last dose of study treatment. The number of participants with B-cell recovery from End of Treatment to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) [PD before B-cell recovery or PD within 45 days after recovery] or Recovery without PD. PD required one of the following: 50% increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50% increase in the longest diameter of any previous site of lymphadenopathy, 50% increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology.
Time Frame Up to 4 years, 5 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the Safety Evaluable Population, all randomized participants who received at least one dose of study drug, with B-Cell depletion.
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description:
Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
Overall Number of Participants Analyzed 40 38
Measure Type: Number
Unit of Measure: Participants
Up to 6 Months FU: Recovery with PD (n=30, 31) 0 0
Up to 6 Months FU: Recovery without PD (n=30, 31) 2 3
6-12 Months FU: Recovery with PD (n=24, 24) 1 0
6-12 Months FU: Recovery without PD (n=24, 24) 7 7
12-18 Months FU: Recovery with PD (n=17, 17) 0 0
12-18 Months FU: Recovery without PD (n=17, 17) 6 8
18-24 Months FU: Recovery with PD (n=10, 9) 0 0
18-24 Months FU: Recovery without PD (n=10, 9) 5 1
24-30 Months FU: Recovery with PD (n=4, 6) 0 0
24-30 Months FU: Recovery without PD (n=4, 6) 2 1
30-36 Months FU: Recovery with PD (n=1, 3) 0 0
30-36 Months FU: Recovery without PD (n=1, 3) 0 0
36-42 Months FU: Recovery with PD (n=0, 0) 0 0
36-42 Months FU: Recovery without PD (n=0, 0) 0 0
After 42 Months FU: Recovery with PD (n=0, 0) 0 0
After 42 Months FU: Recovery without PD (n=0, 0) 0 0
Time Frame Up to 4 years, 5 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Hide Arm/Group Description Participants received a 1000 mg intravenous (IV) infusion, on days 1 (split dose 100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of cycle 1 and day 1 of cycles 2 - 8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose. Participants received a 2000 mg IV infusion, on days 1 (split dose 100 mg Day 1, 900 mg Day 2 and 1000 mg Day 3), 8 and 15 of cycle 1 and day 1 of cycles 2 -8, 21 day cycles. All participants received corticosteroids IV prior to the initial dose.
All-Cause Mortality
Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   8/40 (20.00%)   8/38 (21.05%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  2/40 (5.00%)  1/38 (2.63%) 
Neutropenia  1  0/40 (0.00%)  1/38 (2.63%) 
Thrombocytopenia  1  0/40 (0.00%)  1/38 (2.63%) 
Cardiac disorders     
Acute coronary syndrome  1  0/40 (0.00%)  1/38 (2.63%) 
Myocardial infarction  1  1/40 (2.50%)  0/38 (0.00%) 
Sinus bradycardia  1  0/40 (0.00%)  1/38 (2.63%) 
General disorders     
Chest pain  1  1/40 (2.50%)  0/38 (0.00%) 
Pyrexia  1  1/40 (2.50%)  0/38 (0.00%) 
Infections and infestations     
Sepsis  1  0/40 (0.00%)  1/38 (2.63%) 
Sinusitis  1  1/40 (2.50%)  0/38 (0.00%) 
Urinary tract infection  1  1/40 (2.50%)  0/38 (0.00%) 
Urosepsis  1  0/40 (0.00%)  1/38 (2.63%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  2/40 (5.00%)  0/38 (0.00%) 
Fall  1  0/40 (0.00%)  1/38 (2.63%) 
Rib fracture  1  0/40 (0.00%)  1/38 (2.63%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  0/40 (0.00%)  1/38 (2.63%) 
Nervous system disorders     
Depressed level of consciousness  1  1/40 (2.50%)  0/38 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Hypoxia  1  1/40 (2.50%)  0/38 (0.00%) 
Emphysema  1  0/40 (0.00%)  1/38 (2.63%) 
Vascular disorders     
Hypotension  1  1/40 (2.50%)  0/38 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Obinutuzumab 1000 mg Obinutuzumab 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   40/40 (100.00%)   38/38 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia  1  14/40 (35.00%)  12/38 (31.58%) 
Thrombocytopenia  1  9/40 (22.50%)  7/38 (18.42%) 
Anaemia  1  7/40 (17.50%)  3/38 (7.89%) 
Febrile Neutropenia  1  2/40 (5.00%)  1/38 (2.63%) 
Ear and labyrinth disorders     
Vertigo  1  2/40 (5.00%)  1/38 (2.63%) 
Eye disorders     
Lacrimation increased  1  1/40 (2.50%)  2/38 (5.26%) 
Visual impairment  1  1/40 (2.50%)  2/38 (5.26%) 
Vision Blurred  1  0/40 (0.00%)  2/38 (5.26%) 
Gastrointestinal disorders     
Nausea  1  15/40 (37.50%)  10/38 (26.32%) 
Vomiting  1  11/40 (27.50%)  5/38 (13.16%) 
Diarrhoea  1  3/40 (7.50%)  7/38 (18.42%) 
Constipation  1  3/40 (7.50%)  5/38 (13.16%) 
Abdominal pain  1  3/40 (7.50%)  4/38 (10.53%) 
Dyspepsia  1  1/40 (2.50%)  4/38 (10.53%) 
Gastrooesophageal reflux disease  1  2/40 (5.00%)  2/38 (5.26%) 
Abdominal discomfort  1  2/40 (5.00%)  0/38 (0.00%) 
Dry mouth  1  0/40 (0.00%)  2/38 (5.26%) 
General disorders     
Pyrexia  1  16/40 (40.00%)  18/38 (47.37%) 
Fatigue  1  16/40 (40.00%)  12/38 (31.58%) 
Chills  1  8/40 (20.00%)  7/38 (18.42%) 
Oedema peripheral  1  6/40 (15.00%)  6/38 (15.79%) 
Chest discomfort  1  3/40 (7.50%)  4/38 (10.53%) 
Asthenia  1  3/40 (7.50%)  0/38 (0.00%) 
Influenza like illness  1  0/40 (0.00%)  2/38 (5.26%) 
Chest Pain  1  2/40 (5.00%)  0/38 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  5/40 (12.50%)  6/38 (15.79%) 
Urinary tract infection  1  2/40 (5.00%)  3/38 (7.89%) 
Sinusitis  1  2/40 (5.00%)  2/38 (5.26%) 
Fungal skin infection  1  2/40 (5.00%)  0/38 (0.00%) 
Rhinitis  1  2/40 (5.00%)  0/38 (0.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  30/40 (75.00%)  24/38 (63.16%) 
Contusion  1  0/40 (0.00%)  3/38 (7.89%) 
Laceration  1  2/40 (5.00%)  1/38 (2.63%) 
Fall  1  1/40 (2.50%)  2/38 (5.26%) 
Investigations     
Blood magnesium decreased  1  0/40 (0.00%)  2/38 (5.26%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/40 (10.00%)  3/38 (7.89%) 
Hyperglycaemia  1  2/40 (5.00%)  0/38 (0.00%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  2/40 (5.00%)  4/38 (10.53%) 
Muscle spasms  1  2/40 (5.00%)  3/38 (7.89%) 
Myalgia  1  3/40 (7.50%)  3/38 (7.89%) 
Back pain  1  3/40 (7.50%)  3/38 (7.89%) 
Musculoskeletal pain  1  4/40 (10.00%)  0/38 (0.00%) 
Neck pain  1  3/40 (7.50%)  1/38 (2.63%) 
Pain in extremity  1  2/40 (5.00%)  1/38 (2.63%) 
Muscular weakness  1  0/40 (0.00%)  2/38 (5.26%) 
Musculoskeletal chest pain  1  2/40 (5.00%)  0/38 (0.00%) 
Arthralgia  1  3/40 (7.50%)  3/38 (7.89%) 
Nervous system disorders     
Dizziness  1  10/40 (25.00%)  7/38 (18.42%) 
Headache  1  11/40 (27.50%)  4/38 (10.53%) 
Dysgeusia  1  2/40 (5.00%)  3/38 (7.89%) 
Tremor  1  2/40 (5.00%)  2/38 (5.26%) 
Memory impairment  1  2/40 (5.00%)  0/38 (0.00%) 
Peripheral sensory neuropathy  1  0/40 (0.00%)  2/38 (5.26%) 
Somnolence  1  2/40 (5.00%)  0/38 (0.00%) 
Syncope  1  2/40 (5.00%)  0/38 (0.00%) 
Psychiatric disorders     
Insomnia  1  6/40 (15.00%)  7/38 (18.42%) 
Depression  1  2/40 (5.00%)  2/38 (5.26%) 
Renal and urinary disorders     
Nocturia  1  2/40 (5.00%)  0/38 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  6/40 (15.00%)  11/38 (28.95%) 
Cough  1  6/40 (15.00%)  8/38 (21.05%) 
Oropharyngeal pain  1  1/40 (2.50%)  2/38 (5.26%) 
Dysphonia  1  0/40 (0.00%)  2/38 (5.26%) 
Hiccups  1  0/40 (0.00%)  2/38 (5.26%) 
Hypoxia  1  2/40 (5.00%)  0/38 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  3/40 (7.50%)  6/38 (15.79%) 
Hyperhidrosis  1  3/40 (7.50%)  4/38 (10.53%) 
Night sweats  1  2/40 (5.00%)  3/38 (7.89%) 
Pruritus  1  3/40 (7.50%)  1/38 (2.63%) 
Erythema  1  0/40 (0.00%)  3/38 (7.89%) 
Alopecia  1  2/40 (5.00%)  0/38 (0.00%) 
Skin ulcer  1  0/40 (0.00%)  2/38 (5.26%) 
Vascular disorders     
Flushing  1  8/40 (20.00%)  9/38 (23.68%) 
Hypotension  1  6/40 (15.00%)  4/38 (10.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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: Hoffman-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01414205     History of Changes
Other Study ID Numbers: GAO4768g
GO25677 ( Other Identifier: Hoffmann-La Roche )
First Submitted: August 10, 2011
First Posted: August 11, 2011
Results First Submitted: March 21, 2014
Results First Posted: April 24, 2014
Last Update Posted: April 17, 2017