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A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)

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ClinicalTrials.gov Identifier: NCT01300247
Recruitment Status : Completed
First Posted : February 21, 2011
Results First Posted : June 24, 2016
Last Update Posted : February 2, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphocytic Leukemia, Chronic
Interventions Drug: Fludarabine
Drug: Obinutuzumab
Drug: Bendamustine
Drug: Cyclophosphamide
Enrollment 41
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 milligrams [mg] intravenous [IV] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 milligrams per meter square [mg/m^2] IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2). Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Period Title: Overall Study
Started 21 20
Completed 17 18
Not Completed 4 2
Reason Not Completed
Death             1             1
Lost to Follow-up             2             0
Withdrawal by Subject             1             0
Non-Compliance             0             1
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine Total
Hide Arm/Group Description Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2). Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6). Total of all reporting groups
Overall Number of Baseline Participants 21 20 41
Hide Baseline Analysis Population Description
Safety-Evaluable population included all participants who received any amount of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 20 participants 41 participants
57.8  (11.1) 62.0  (9.0) 59.8  (10.2)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 20 participants 41 participants
Female
4
  19.0%
5
  25.0%
9
  22.0%
Male
17
  81.0%
15
  75.0%
32
  78.0%
1.Primary Outcome
Title Number of Participants With Human Anti-Human Antibodies (HAHAs)
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: participants
0 0
2.Secondary Outcome
Title Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab
Hide Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Obinutuzumab
Hide Description [Not Specified]
Time Frame Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Obinutuzumab
Hide Description [Not Specified]
Time Frame Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1
Hide Outcome Measure Data
Hide Analysis Population Description
The PK variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Clearance of Obinutuzumab
Hide Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Pre-dose on C1D1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Volume of Distribution of Obinutuzumab
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Half-Life of Obinutuzumab
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK variables could not be calculated as the PK samples were not collected accurately.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
Hide Description Objective response was defined as a complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR), as determined by investigator. CR:required peripheral blood lymphocytes <4x10^9/L; absence of lymphadenopathy; no hepatomegaly or splenomegaly by physical examination as determined by measurement below relevant costal margin; absence of disease/constitutional symptoms; bone marrow at least normocellular for age, with <30% of nucleated cells being lymphocytes. PR:Greater than equal to (>=) 50% decrease in peripheral blood lymphocyte count, >=50% reduction in lymphadenopathy, >=50% reduction of liver and/or spleen enlargement, either neutrophil, platelet, or hemoglobin (Hb) recovery. CRi:met all CR criteria including confirmed lymphocyte infiltration <30%; may not meet Hb, platelet or neutrophil count recovery. The 95% confidence interval (CI) was estimated by Clopper-Pearson method. The end of treatment response visit occurred 2-3 months after end of treatment.
Time Frame Baseline up to relapse or progression or death from any cause, whichever occurred first up to end of treatment response visit (up to approximately 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.9
(38.44 to 81.89)
90.0
(68.30 to 98.77)
9.Secondary Outcome
Title Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines
Hide Description DOR for participants with OR: time from first CR, CRi or PR to disease progression (DP), relapse, or death, assessed by the investigator. DP: >=50% increase in lymphocytes to at least 5x10^9/L;new palpable lymph nodes (>15 millimeters [mm] in longest diameter) or any new extra-nodal lesion; >=50% increase in the longest diameter of any previous site of lymphadenopathy; >=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology. CR:peripheral blood lymphocytes (PBL) <4x10^9/L; no lymphadenopathy; no hepatomegaly or splenomegaly (below relevant costal margin); no symptoms; bone marrow at least normocellular for age, with <30% of nucleated cells being lymphocytes. PR: >=50% decrease in PBL, >=50% reduction in lymphadenopathy, >=50% reduction of liver and/or spleen enlargement, either neutrophil, platelet, or hemoglobin (Hb) recovery. CRi: met CR criteria, lymphocyte infiltration <30%; may not meet Hb, platelet or neutrophil count recovery.
Time Frame From first documented objective response up to disease progression or relapse or death, whichever occurred first (up to approximately 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
NA [1] 
(NA to NA)
100.00
(100.00 to 100.00)
[1]
Not estimated as not enough data captured in this arm at 6 months
10.Secondary Outcome
Title Percentage of Participants Who Were Alive and Progression Free
Hide Description Progressive disease assessed using IWCLL: >=50% increase in the absolute number of circulating lymphocytes to at least 5x10^9/L; Appearance of new palpable lymph nodes (>15 millimeters [mm] in longest diameter) or any new extra-nodal lesion; >=50% increase in the longest diameter of any previous site of lymphadenopathy; >=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology.
Time Frame Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: percentage of participants
90.5 90.0
11.Secondary Outcome
Title Percentage of Participants Who Were Alive
Hide Description [Not Specified]
Time Frame Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population.
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: percentage of participants
95.2 95.0
12.Secondary Outcome
Title Percentage of Participants Who Had B-Cell Depletion
Hide Description B-cell depletion was defined as cluster of differentiation 19 (CD19) <0.07×10^9/L and could occur only after at least one dose of study drug had been administered.
Time Frame Up to the end of the treatment period, and follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: percentage of participants
End of the treatment period 90.5 100.0
Follow-up at 6 months 85.7 100.0
Within 6-12 months of follow-up 81.0 100.0
After 12 months follow-up 47.6 70.0
13.Secondary Outcome
Title Percentage of Participants Who Had B-Cell Recovery
Hide Description B-cell recovery was defined as CD19 >=0.07×10^9/L, where participants’ CD19 were previously depleted. B-cell recovery was only considered possible when the participant had received the last dose of study treatment.
Time Frame Follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety evaluable population
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description:
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2).
Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
Overall Number of Participants Analyzed 21 20
Measure Type: Number
Unit of Measure: percentage of participants
Follow-up at 6 months 0 0
Within 6-12 months of follow-up 9.5 0
After 12 months follow-up 42.9 30.0
Time Frame Up to the end of the study (up to approximately 4 years).
Adverse Event Reporting Description All adverse events (related and unrelated to treatment) were to be collected up to 28 days after the last dose of obinutuzumab. After 28 days after the last dose of obinutuzumab, investigators were to report only serious adverse events that were attributed to obinutuzumab; these were to be reported to Genentech/Roche Drug Safety indefinitely (even if the study was closed). Significant abnormalities in laboratory parameters were reported as adverse events.
 
Arm/Group Title Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Hide Arm/Group Description Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6) and cyclophosphamide 250 mg/m^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6). The Cycle 1 Day 1 dose of obinutuzumab was split over two days (Cycle 1 Day 1 and Cycle 1 Day 2). Participants received 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).
All-Cause Mortality
Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Affected / at Risk (%) Affected / at Risk (%)
Total   6/21 (28.57%)   11/20 (55.00%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  3/21 (14.29%)  2/20 (10.00%) 
Leukopenia * 1  0/21 (0.00%)  1/20 (5.00%) 
Neutropenia * 1  0/21 (0.00%)  1/20 (5.00%) 
Cardiac disorders     
Tachycardia * 1  0/21 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders     
Nausea * 1  1/21 (4.76%)  1/20 (5.00%) 
Vomiting * 1  1/21 (4.76%)  1/20 (5.00%) 
Diarrhoea * 1  1/21 (4.76%)  0/20 (0.00%) 
General disorders     
Pyrexia * 1  0/21 (0.00%)  2/20 (10.00%) 
Fatigue * 1  0/21 (0.00%)  1/20 (5.00%) 
Infections and infestations     
Appendicitis * 1  1/21 (4.76%)  0/20 (0.00%) 
Cellulitis * 1  1/21 (4.76%)  0/20 (0.00%) 
Pneumonia * 1  1/21 (4.76%)  0/20 (0.00%) 
Skin infection * 1  0/21 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  0/21 (0.00%)  3/20 (15.00%) 
Investigations     
Neutrophil count decreased * 1  1/21 (4.76%)  0/20 (0.00%) 
Metabolism and nutrition disorders     
Tumour lysis syndrome * 1  0/21 (0.00%)  1/20 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Small cell lung cancer * 1  0/21 (0.00%)  1/20 (5.00%) 
Squamous cell carcinoma * 1  0/21 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Syncope * 1  0/21 (0.00%)  1/20 (5.00%) 
Psychiatric disorders     
Mental status changes * 1  0/21 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonitis * 1  0/21 (0.00%)  1/20 (5.00%) 
Pneumothorax * 1  0/21 (0.00%)  1/20 (5.00%) 
Respiratory failure * 1  0/21 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders     
Swelling face * 1  0/21 (0.00%)  1/20 (5.00%) 
Vascular disorders     
Hypertension * 1  0/21 (0.00%)  1/20 (5.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Obinutuzumab + Fludarabine + Cyclophosphamide Obinutuzumab + Bendamustine
Affected / at Risk (%) Affected / at Risk (%)
Total   21/21 (100.00%)   20/20 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia * 1  5/21 (23.81%)  10/20 (50.00%) 
Anaemia * 1  5/21 (23.81%)  3/20 (15.00%) 
Thrombocytopenia * 1  3/21 (14.29%)  5/20 (25.00%) 
Febrile neutropenia * 1  2/21 (9.52%)  0/20 (0.00%) 
Cytopenia * 1  0/21 (0.00%)  2/20 (10.00%) 
Lymphadenopathy * 1  0/21 (0.00%)  1/20 (5.00%) 
Leukopenia * 1  0/21 (0.00%)  1/20 (5.00%) 
Cardiac disorders     
Tachycardia * 1  0/21 (0.00%)  1/20 (5.00%) 
Ear and labyrinth disorders     
Vertigo * 1  0/21 (0.00%)  1/20 (5.00%) 
Eye disorders     
Vision blurred * 1  1/21 (4.76%)  1/20 (5.00%) 
Gastrointestinal disorders     
Nausea * 1  16/21 (76.19%)  12/20 (60.00%) 
Constipation * 1  10/21 (47.62%)  7/20 (35.00%) 
Vomiting * 1  7/21 (33.33%)  2/20 (10.00%) 
Diarrhoea * 1  4/21 (19.05%)  10/20 (50.00%) 
Abdominal pain * 1  1/21 (4.76%)  2/20 (10.00%) 
Dyspepsia * 1  1/21 (4.76%)  2/20 (10.00%) 
Epigastric discomfort * 1  1/21 (4.76%)  2/20 (10.00%) 
Dysphagia * 1  0/21 (0.00%)  2/20 (10.00%) 
Gastrooesophageal reflux disease * 1  2/21 (9.52%)  0/20 (0.00%) 
Abdominal distension * 1  0/21 (0.00%)  1/20 (5.00%) 
Abdominal pain upper * 1  0/21 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorder * 1  0/21 (0.00%)  1/20 (5.00%) 
Mouth ulceration * 1  0/21 (0.00%)  1/20 (5.00%) 
Stomatitis * 1  0/21 (0.00%)  1/20 (5.00%) 
General disorders     
Fatigue * 1  12/21 (57.14%)  7/20 (35.00%) 
Pyrexia * 1  5/21 (23.81%)  8/20 (40.00%) 
Chills * 1  2/21 (9.52%)  7/20 (35.00%) 
Oedema peripheral * 1  2/21 (9.52%)  1/20 (5.00%) 
Pain * 1  0/21 (0.00%)  3/20 (15.00%) 
Asthenia * 1  1/21 (4.76%)  1/20 (5.00%) 
Injection site pain * 1  0/21 (0.00%)  2/20 (10.00%) 
Axillary pain * 1  0/21 (0.00%)  1/20 (5.00%) 
Catheter site pain * 1  0/21 (0.00%)  1/20 (5.00%) 
Chest discomfort * 1  0/21 (0.00%)  1/20 (5.00%) 
Malaise * 1  0/21 (0.00%)  1/20 (5.00%) 
Mucosal inflammation * 1  0/21 (0.00%)  1/20 (5.00%) 
Adverse drug reaction * 1  1/21 (4.76%)  1/20 (5.00%) 
Immune system disorders     
Drug hypersensitivity * 1  0/21 (0.00%)  1/20 (5.00%) 
Cytokine release syndrome * 1  0/21 (0.00%)  1/20 (5.00%) 
Hypersensitivity * 1  0/21 (0.00%)  1/20 (5.00%) 
Infections and infestations     
Upper respiratory tract infection * 1  4/21 (19.05%)  3/20 (15.00%) 
Sinusitis * 1  0/21 (0.00%)  3/20 (15.00%) 
Urinary tract infection * 1  3/21 (14.29%)  0/20 (0.00%) 
Bronchitis * 1  1/21 (4.76%)  1/20 (5.00%) 
Candida infection * 1  2/21 (9.52%)  0/20 (0.00%) 
Paronychia * 1  2/21 (9.52%)  0/20 (0.00%) 
Tooth infection * 1  2/21 (9.52%)  0/20 (0.00%) 
Clostridium difficile infection * 1  0/21 (0.00%)  1/20 (5.00%) 
Herpes zoster * 1  1/21 (4.76%)  1/20 (5.00%) 
Pharyngitis * 1  0/21 (0.00%)  1/20 (5.00%) 
Pneumonia * 1  0/21 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  16/21 (76.19%)  11/20 (55.00%) 
Contusion * 1  0/21 (0.00%)  1/20 (5.00%) 
Skin Abrasion * 1  0/21 (0.00%)  1/20 (5.00%) 
Investigations     
Alanine aminotransferase increased * 1  4/21 (19.05%)  1/20 (5.00%) 
Aspartate aminotransferase increased * 1  3/21 (14.29%)  1/20 (5.00%) 
Blood creatinine increased * 1  0/21 (0.00%)  1/20 (5.00%) 
Electrocardiogram QT prolonged * 1  0/21 (0.00%)  1/20 (5.00%) 
Transaminases increased * 1  0/21 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  2/21 (9.52%)  3/20 (15.00%) 
Hypocalcaemia * 1  0/21 (0.00%)  5/20 (25.00%) 
Hypokalaemia * 1  0/21 (0.00%)  3/20 (15.00%) 
Hypomagnesaemia * 1  0/21 (0.00%)  2/20 (10.00%) 
Hyponatraemia * 1  0/21 (0.00%)  2/20 (10.00%) 
Decreased appetite * 1  0/21 (0.00%)  1/20 (5.00%) 
Gout * 1  0/21 (0.00%)  1/20 (5.00%) 
Hyperphosphataemia * 1  0/21 (0.00%)  1/20 (5.00%) 
Vitamin D deficiency * 1  0/21 (0.00%)  1/20 (5.00%) 
Hyperkalaemia * 1  0/21 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders     
Bone pain * 1  2/21 (9.52%)  4/20 (20.00%) 
Arthralgia * 1  1/21 (4.76%)  3/20 (15.00%) 
Muscle spasms * 1  2/21 (9.52%)  1/20 (5.00%) 
Back pain * 1  0/21 (0.00%)  2/20 (10.00%) 
Joint swelling * 1  0/21 (0.00%)  2/20 (10.00%) 
Muscular weakness * 1  1/21 (4.76%)  1/20 (5.00%) 
Pain in extremity * 1  2/21 (9.52%)  1/20 (5.00%) 
Flank pain * 1  0/21 (0.00%)  1/20 (5.00%) 
Musculoskeletal pain * 1  0/21 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Dizziness * 1  2/21 (9.52%)  5/20 (25.00%) 
Headache * 1  0/21 (0.00%)  5/20 (25.00%) 
Memory impairment * 1  0/21 (0.00%)  2/20 (10.00%) 
Aphonia * 1  0/21 (0.00%)  1/20 (5.00%) 
Balance disorder * 1  0/21 (0.00%)  1/20 (5.00%) 
Disturbance in attention * 1  0/21 (0.00%)  1/20 (5.00%) 
Hypoaesthesia * 1  0/21 (0.00%)  1/20 (5.00%) 
Muscle contractions involuntary * 1  0/21 (0.00%)  1/20 (5.00%) 
Neuropathy peripheral * 1  0/21 (0.00%)  1/20 (5.00%) 
Restless leg syndrome * 1  0/21 (0.00%)  1/20 (5.00%) 
Somnolence * 1  0/21 (0.00%)  1/20 (5.00%) 
Psychiatric disorders     
Insomnia * 1  4/21 (19.05%)  3/20 (15.00%) 
Anxiety * 1  0/21 (0.00%)  5/20 (25.00%) 
Communication disorder * 1  0/21 (0.00%)  1/20 (5.00%) 
Depression * 1  0/21 (0.00%)  1/20 (5.00%) 
Renal and urinary disorders     
Pollakiuria * 1  2/21 (9.52%)  0/20 (0.00%) 
Dysuria * 1  0/21 (0.00%)  1/20 (5.00%) 
Acute kidney injury * 1  0/21 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/21 (9.52%)  6/20 (30.00%) 
Dyspnoea * 1  3/21 (14.29%)  3/20 (15.00%) 
Dysphonia * 1  1/21 (4.76%)  1/20 (5.00%) 
Oropharyngeal pain * 1  0/21 (0.00%)  2/20 (10.00%) 
Pleural effusion * 1  0/21 (0.00%)  2/20 (10.00%) 
Productive cough * 1  0/21 (0.00%)  2/20 (10.00%) 
Dyspnoea exertional * 1  0/21 (0.00%)  1/20 (5.00%) 
Hiccups * 1  0/21 (0.00%)  1/20 (5.00%) 
Pulmonary oedema * 1  0/21 (0.00%)  1/20 (5.00%) 
Throat irritation * 1  0/21 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  2/21 (9.52%)  5/20 (25.00%) 
Pruritus * 1  1/21 (4.76%)  4/20 (20.00%) 
Erythema * 1  1/21 (4.76%)  2/20 (10.00%) 
Dry skin * 1  1/21 (4.76%)  1/20 (5.00%) 
Petechiae * 1  0/21 (0.00%)  2/20 (10.00%) 
Pruritus generalized * 1  0/21 (0.00%)  2/20 (10.00%) 
Rash maculo-papular * 1  0/21 (0.00%)  2/20 (10.00%) 
Rash pruritic * 1  2/21 (9.52%)  0/20 (0.00%) 
Acne * 1  0/21 (0.00%)  1/20 (5.00%) 
Butterfly rash * 1  0/21 (0.00%)  1/20 (5.00%) 
Eczema nummular * 1  0/21 (0.00%)  1/20 (5.00%) 
Hyperhidrosis * 1  0/21 (0.00%)  1/20 (5.00%) 
Psoriasis * 1  0/21 (0.00%)  1/20 (5.00%) 
Rash erythematous * 1  0/21 (0.00%)  1/20 (5.00%) 
Rash generalized * 1  0/21 (0.00%)  1/20 (5.00%) 
Rash macular * 1  0/21 (0.00%)  1/20 (5.00%) 
Surgical and medical procedures     
Radiotherapy * 1  0/21 (0.00%)  1/20 (5.00%) 
Sinus operation * 1  0/21 (0.00%)  1/20 (5.00%) 
Vascular disorders     
Flushing * 1  1/21 (4.76%)  4/20 (20.00%) 
Hypotension * 1  1/21 (4.76%)  2/20 (10.00%) 
Phlebitis * 1  0/21 (0.00%)  1/20 (5.00%) 
Haematoma * 1  0/21 (0.00%)  1/20 (5.00%) 
Hypertension * 1  0/21 (0.00%)  1/20 (5.00%) 
Intermittent claudication * 1  0/21 (0.00%)  1/20 (5.00%) 
Phlebitis superficial * 1  0/21 (0.00%)  2/20 (10.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
The interim data reported here (up to clinical cutoff date of 24 January 2013) were for participants who had completed treatment response assessment, which took place approximately 2 months after the last infusion of study treatment.
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: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01300247     History of Changes
Other Study ID Numbers: GAO4779g
GO01298 ( Other Identifier: Hoffmann-La Roche )
First Submitted: February 14, 2011
First Posted: February 21, 2011
Results First Submitted: May 18, 2016
Results First Posted: June 24, 2016
Last Update Posted: February 2, 2017