Lymphocytic Leukemia, Chronic
Conditions
Brief summary
This open-label, 2-arm, nonrandomized, multicenter, Phase Ib study will investigate the safety and efficacy of obinutuzumab (RO5072759; GA101) administered in combination with chemotherapy (bendamustine or fludarabine + cyclophosphamide \[FC\] regimens) in participants with previously untreated cluster of differentiation 20 (CD20)-positive B-CLL. Participants will be enrolled to receive a maximum of 6 cycles of obinutuzumab (1000 milligrams \[mg\] intravenous \[IV\] infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus bendamustine (90 milligrams per meter square \[mg/m\^2\] IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2 - 6) on 28 day cycles or a maximum of 6 cycles of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2 - 6) plus FC (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; 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) on 28 day cycles.
Interventions
DRUGCyclophosphamide
Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.
DRUGFludarabine
Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.
DRUGObinutuzumab
Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.
DRUGBendamustine
Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of CD20-positive B-CLL * Rai Stage III/IV or Binet Stage C disease * Rai Stage I/II or Binet Stage B disease that requires treatment * Adequate baseline bone marrow function, unless there is clear evidence of extensive bone marrow involvement with tumor infiltration, myelodysplasia, or hypocellularity * No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Life expectancy of greater than (\>) 6 months
Exclusion criteria
* Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1 * Transformation of CLL to aggressive B-cell malignancy * Creatinine clearance less than equal to (\<=) 60 milliliters per minute (mL/min), calculated according to the formula of Cockcroft and Gault * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times the upper limit of normal (ULN) * Total bilirubin greater than equal to (\>=) 3 x ULN * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy * History of sensitivity to mannitol (if bendamustine is to be administered) * History of other malignancy that could affect compliance with the protocol or interpretation of results * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease * Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1 * Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis * Known infection with human immunodeficiency virus (HIV) seropositive status * Presence of positive test results for hepatitis B (hepatitis B virus \[HBV\] surface antigen \[HBsAg\] and/or total hepatitis B core antibody \[anti-HBc\]) or hepatitis C (hepatitis C virus \[HCV\] antibody serology testing). Participants with chronic HBV infection, occult HBV infection, or past HBV infection will be excluded. Participants who have received IV immunoglobulin within 3 months of enrollment and who are anti-HBc positive but HBV deoxyribonucleic acid (DNA) negative will be considered for inclusion on the study by the Medical Monitor on a case-by-case basis. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). * Women who are pregnant or lactating * Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly * Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid use except low-dose corticosteroid therapy used to treat an illness other than lymphoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Human Anti-Human Antibodies (HAHAs) | Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Obinutuzumab | 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) | — |
| Trough Plasma Concentration (Ctrough) of Obinutuzumab | Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1 | — |
| Clearance of Obinutuzumab | 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) | 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. |
| Volume of Distribution of Obinutuzumab | 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) | 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. |
| Half-Life of Obinutuzumab | 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) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab | 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) | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines | From first documented objective response up to disease progression or relapse or death, whichever occurred first (up to approximately 6 months) | 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. |
| Percentage of Participants Who Were Alive and Progression Free | Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years) | 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. |
| Percentage of Participants Who Were Alive | Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years) | — |
| Percentage of Participants Who Had B-Cell Depletion | 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) | 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. |
| Percentage of Participants Who Had B-Cell Recovery | Follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years) | 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. |
| Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines | 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide 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). | 21 |
| Obinutuzumab + Bendamustine 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). | 20 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Non-Compliance | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Obinutuzumab + Fludarabine + Cyclophosphamide | Obinutuzumab + Bendamustine | Total |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 11.1 | 62.0 years STANDARD_DEVIATION 9 | 59.8 years STANDARD_DEVIATION 10.2 |
| Gender Female | 4 Participants | 5 Participants | 9 Participants |
| Gender Male | 17 Participants | 15 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 20 / 20 |
| serious Total, serious adverse events | 6 / 21 | 11 / 20 |
Outcome results
Primary
Number of Participants With Human Anti-Human Antibodies (HAHAs)
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)
Population: Safety evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Number of Participants With Human Anti-Human Antibodies (HAHAs) | 0 participants |
| Obinutuzumab + Bendamustine | Number of Participants With Human Anti-Human Antibodies (HAHAs) | 0 participants |
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab
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)
Population: The pharmacokinetic (PK) variables could not be calculated as the PK samples were not collected accurately.
Secondary
Clearance of Obinutuzumab
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)
Population: The PK variables could not be calculated as the PK samples were not collected accurately.
Secondary
Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines
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)
Population: Safety evaluable population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines | NA percentage of participants |
| Obinutuzumab + Bendamustine | Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines | 100.00 percentage of participants |
Secondary
Half-Life of Obinutuzumab
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)
Population: The PK variables could not be calculated as the PK samples were not collected accurately.
Secondary
Maximum Plasma Concentration (Cmax) of Obinutuzumab
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)
Population: The PK variables could not be calculated as the PK samples were not collected accurately.
Secondary
Percentage of Participants Who Had B-Cell Depletion
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)
Population: Safety evaluable population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Depletion | End of the treatment period | 90.5 percentage of participants |
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Depletion | Follow-up at 6 months | 85.7 percentage of participants |
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Depletion | Within 6-12 months of follow-up | 81.0 percentage of participants |
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Depletion | After 12 months follow-up | 47.6 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Depletion | After 12 months follow-up | 70.0 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Depletion | End of the treatment period | 100.0 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Depletion | Within 6-12 months of follow-up | 100.0 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Depletion | Follow-up at 6 months | 100.0 percentage of participants |
Secondary
Percentage of Participants Who Had B-Cell Recovery
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)
Population: Safety evaluable population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Recovery | Follow-up at 6 months | 0 percentage of participants |
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Recovery | Within 6-12 months of follow-up | 9.5 percentage of participants |
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Had B-Cell Recovery | After 12 months follow-up | 42.9 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Recovery | Follow-up at 6 months | 0 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Recovery | Within 6-12 months of follow-up | 0 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Had B-Cell Recovery | After 12 months follow-up | 30.0 percentage of participants |
Secondary
Percentage of Participants Who Were Alive
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)
Population: Safety evaluable population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Were Alive | 95.2 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Were Alive | 95.0 percentage of participants |
Secondary
Percentage of Participants Who Were Alive and Progression Free
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)
Population: Safety evaluable population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants Who Were Alive and Progression Free | 90.5 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants Who Were Alive and Progression Free | 90.0 percentage of participants |
Secondary
Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
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)
Population: Safety evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab + Fludarabine + Cyclophosphamide | Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines | 61.9 percentage of participants |
| Obinutuzumab + Bendamustine | Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines | 90.0 percentage of participants |
Secondary
Trough Plasma Concentration (Ctrough) of Obinutuzumab
Time frame: Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1
Population: The PK variables could not be calculated as the PK samples were not collected accurately.
Secondary
Volume of Distribution of Obinutuzumab
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)
Population: The PK variables could not be calculated as the PK samples were not collected accurately.