Trial Outcomes & Findings for A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL) (NCT NCT00545714)
NCT ID: NCT00545714
Last Updated: 2019-01-16
Results Overview
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (\<) 4000 per cubic millimeter (mm\^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (\>) 1500/mm\^3, platelets (Plt) \>100,000/mm\^3, hemoglobin (Hb) \>11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
86 participants
Primary outcome timeframe
Month 9
Results posted on
2019-01-16
Participant Flow
A total of 86 participants were enrolled in 29 centers in Spain in this two-phase study (Induction Phase and Maintenance Phase).
Participant milestones
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
Participants received rituximab 375 milligrams per square meter (mg/m\^2) as intravenous (IV) infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a partial response (PR) or complete response (CR) and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Induction Phase (6 Months)
STARTED
|
86
|
|
Induction Phase (6 Months)
Safety Population
|
86
|
|
Induction Phase (6 Months)
Intent-to-Treat (ITT) Population
|
84
|
|
Induction Phase (6 Months)
COMPLETED
|
74
|
|
Induction Phase (6 Months)
NOT COMPLETED
|
12
|
|
Maintenance Phase (36 Months)
STARTED
|
74
|
|
Maintenance Phase (36 Months)
COMPLETED
|
42
|
|
Maintenance Phase (36 Months)
NOT COMPLETED
|
32
|
Reasons for withdrawal
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
Participants received rituximab 375 milligrams per square meter (mg/m\^2) as intravenous (IV) infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a partial response (PR) or complete response (CR) and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Induction Phase (6 Months)
Physician Decision
|
3
|
|
Induction Phase (6 Months)
Unacceptable Toxicity
|
6
|
|
Induction Phase (6 Months)
Disease Progression
|
1
|
|
Induction Phase (6 Months)
Eligibility Criteria Violation
|
2
|
|
Maintenance Phase (36 Months)
Unacceptable Toxicity
|
16
|
|
Maintenance Phase (36 Months)
Disease Progression
|
9
|
|
Maintenance Phase (36 Months)
Physician Decision
|
1
|
|
Maintenance Phase (36 Months)
Protocol Violation
|
1
|
|
Maintenance Phase (36 Months)
Withdrawal by Subject
|
3
|
|
Maintenance Phase (36 Months)
Death
|
2
|
Baseline Characteristics
A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Age, Continuous
|
57.92 Years
STANDARD_DEVIATION 7.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
57 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Month 9Population: ITT Population included all participants who received at least one dose of study drug and met inclusion/exclusion criteria.
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (\<) 4000 per cubic millimeter (mm\^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (\>) 1500/mm\^3, platelets (Plt) \>100,000/mm\^3, hemoglobin (Hb) \>11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
|
95.2 Percentage of Participants
Interval 88.25 to 98.69
|
SECONDARY outcome
Timeframe: Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.
CR was defined as no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR was defined as decrease \>50% in Lymph in peripheral blood; reduction in ADPs \>50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; \>50% decrease in VSM; Neut \>1500/mm\^3 or \>50% increase from Baseline; Plt \>100,000/mm\^3 or \>50% increase from Baseline; Hb \>11.0 g/dL or \>50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
Post-IP: CR
|
75.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
Post-IP: PR
|
13.1 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (9 Cycles): CR
|
89.4 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (9 Cycles): PR
|
6.4 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (12 Cycles): CR
|
87.9 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (12 Cycles): PR
|
6.1 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (15 Cycles): CR
|
90.9 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (15 Cycles): PR
|
4.5 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (18 Cycles): CR
|
88.1 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
MP (18 Cycles): PR
|
8.5 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
6 Months FU: CR
|
83.3 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
6 Months FU: PR
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
12 Months FU: CR
|
94.4 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
12 Months FU: PR
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
18 Months FU: CR
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
18 Months FU: PR
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
24 Months FU: CR
|
93.1 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
24 Months FU: PR
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
30 Months FU: CR
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
30 Months FU: PR
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
36 Months FU: CR
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
36 Months FU: PR
|
0.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36Population: ITT Population. Only those with negative MRD were included in the analysis. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.
CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR: decrease \>50% in Lymph in peripheral blood; reduction in ADPs \>50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; \>50% decrease in VSM; Neut \>1500/mm\^3 or \>50% increase from Baseline; Plt \>100,000/mm\^3 or \>50% increase from Baseline; Hb \>11.0 g/dL or \>50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR. Negative MRD: Lymph \<0.01% of all white blood cells (WBCs) in blood or BM after two consecutive measurements. Analysis performed only in blood during the Maintenance Phase and Follow-Up.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=60 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
Post-IP: Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
Post-IP: BM MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
MP (9 Cycles): Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
MP (12 Cycles): Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
MP (15 Cycles): Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
MP (18 Cycles): Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
6 Months FU: Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
12 Months FU: Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
18 Months FU: Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
24 Months FU: Blood MRD Negative
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
36 Months FU: Blood MRD Negative
|
100.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)Population: ITT Population
Participants with CRi were those who met all CR criteria (including BM examinations) but had persistent anemia, thrombocytopenia, or neutropenia apparently unrelated to chronic lymphocytic leukemia (CLL) but related to drug toxicity. CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood \<4000/mm\^3; normalization of peripheral blood parameters: Neut \>1500/mm\^3, Plt \>100,000/mm\^3, Hb \>11 g/dL without transfusion; normocellular BM with \<30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)
|
7.1 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline up to death due to any cause (up to 92 months)Population: Safety Population
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=86 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants Who Died
|
23.2 Percentage of Participants
Interval 5.72 to
|
SECONDARY outcome
Timeframe: Baseline up to death due to any cause (up to 92 months)Population: ITT Population
OS was defined as time from treatment start to death of the participant. For all other participants, the last follow-up available was taken as the last control. If the participant had not completed the study, the date of the last visit available was considered. OS was estimated using Kaplan-Meier (KM) methodology.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Overall Survival (OS)
|
7.51 Years
Interval 7.5 to
The upper limit of confidence interval (CI) was not estimable due to high number of censored participants.
|
SECONDARY outcome
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)Population: ITT Population
PD was defined as new ADPs (1.5 centimeters \[cm\]), hepato-/splenomegaly (HSM), Richter syndrome (RS), or other infiltrated organs; greater than or equal to (\>/=) 50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With PD or Death
|
39.29 Percentage of Participants
Interval 5.72 to
|
SECONDARY outcome
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)Population: ITT Population
PFS was defined as time from start of study treatment to PD or death, whichever occurred first. For other participants, last follow-up available was taken as last control. If participant did not complete study, date of last visit available was considered. PFS was estimated using KM methodology. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; \>/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Progression-Free Survival (PFS)
|
6.96 Years
Interval 5.72 to
The upper limit of CI was not estimable due to high number of censored participants.
|
SECONDARY outcome
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)Population: ITT Population. Only those who received new chemotherapy/immunotherapy, as per definitions for TFS, were included in the analysis.
TFS was defined time from start of study treatment until participant received new chemotherapy/immunotherapy because of PD and to reduce the disease with palliative or curative intent. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; \>/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase \>/=50% in peripheral blood with B Lymph \>/=5000/mm\^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb \<10 g/dL, \>/=50% decrease in basal Plt count, or count \<100,000/mm\^3 at \>/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=27 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Treatment-Free Survival (TFS)
|
4.13 Years
Interval 2.98 to 4.87
|
SECONDARY outcome
Timeframe: From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)Population: ITT Population. Only those participants who achieved a clinical response of CR or PR were evaluable for this measure.
DOR: time from CR/PR to MRD/PD. PD: new ADP (1.5 cm), HSM, RS, other infiltrated organs or \>/=50% increase size in those with PR; blood Lymph increase \>/=50% with B Lymph \>/=5000/mm\^3; cytopenia due to CLL. Progression of (nonautoimmune) cytopenia: 2-g/dL decrease basal Hb, Hb \<10 g/dL, \>/=50% decrease basal Plt or \<100,000/mm\^3 at \>/=3 months post-treatment was PD if clonal CLL cell infiltration on BM biopsy. CR: no ADP/VSM in PE; no general Sx; blood Lymph \<4000/mm\^3; Neut \>1500/mm\^3; Plt \>100,000/mm\^3; Hb \>11 g/dL (no transfusion); normocellular BM with \<30% Lymph; BM aspirate/biopsy with no lymphoid nodule infiltration. PR: \>50% decrease blood Lymph; \>50% decrease in total sum up to 6 ADPs or baseline ADP of LD, no new/enlargement of prior ADP; \>50% decrease VSM; Neut \>1500/mm\^3 or \>50% increase; Plt \>100,000/mm\^3 or \>50% increase; Hb \>11.0 g/dL or \>50% increase (no transfusion). All CR criteria but persistent anemia or thrombocytopenia was PR. MRD: Lymph \>0.01% of blood/BM WBCs.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=80 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Duration of Response (DOR)
|
NA Years
Median time of response was not estimable due to high number of censored participants.
|
SECONDARY outcome
Timeframe: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.
Percentages of participants with CD38 expression by \>/=30% of CLL cells during the Induction Phase, Maintenance Phase, and Follow-Up were reported.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
Post-IP
|
47.6 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
MP (9 Cycles)
|
44.4 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
MP (12 Cycles)
|
45.5 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
MP (15 Cycles)
|
47.6 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
MP (18 Cycles)
|
47.4 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
6 Months FU
|
66.7 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
12 Months FU
|
45.7 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
18 Months FU
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
24 Months FU
|
41.4 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
30 Months FU
|
50.0 Percentage of Participants
|
|
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
36 Months FU
|
35.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category. Designation of 'MP (xC)' refers to number of cycles in Maintenance Phase.
Percentages of participants with genetic abnormalities (deletion 6q, deletion 11q22-q23, deletion p53, trisomy 12, and deletion 13q14) in the course of the disease during the Induction Phase and Maintenance Phase were reported.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Genetic Abnormalities
MP (12C): Deletion 13q14
|
51.5 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
Post-IP: Deletion 6q
|
3.6 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
Post-IP: Deletion 11q22-q23
|
26.2 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
Post-IP: Deletion p53
|
4.8 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
Post-IP: Trisomy 12
|
15.5 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
Post-IP: Deletion 13q14
|
50.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (9C): Deletion 6q
|
4.3 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (9C): Deletion 11q22-q23
|
25.5 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (9C): Deletion p53
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (9C): Trisomy 12
|
17.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (9C): Deletion 13q14
|
55.3 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (12C): Deletion 6q
|
3.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (12C): Deletion 11q22-q23
|
21.2 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (12C): Deletion p53
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (12C): Trisomy 12 (n= 33)
|
21.2 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (15C): Deletion 6q
|
4.5 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (15C): Deletion 11q22-q23
|
31.8 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (15C): Deletion p53
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (15C): Trisomy 12
|
18.2 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (15C): Deletion 13q14
|
59.1 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (18C): Deletion 6q
|
3.4 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (18C): Deletion 11q22-q23
|
23.7 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (18C): Deletion p53
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (18C): Trisomy 12
|
18.6 Percentage of Participants
|
|
Percentage of Participants With Genetic Abnormalities
MP (18C): Deletion 13q14
|
49.2 Percentage of Participants
|
SECONDARY outcome
Timeframe: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.
Percentages of participants with positive and negative ZAP-70 expression during the Induction Phase, Maintenance Phase, and Follow-Up were reported. Positive ZAP-70 was defined as ZAP-70 expression by \>/=20% of CLL cells. Negative ZAP-70 was defined as ZAP-70 expression by \<20% of CLL cells.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
Post-IP: Positive
|
57.3 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
Post-IP: Negative
|
42.7 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (9 Cycles): Positive
|
57.5 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (9 Cycles): Negative
|
42.5 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (12 Cycles): Positive
|
62.1 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (12 Cycles): Negative
|
37.9 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (15 Cycles): Positive
|
57.1 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (15 Cycles): Negative
|
42.9 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (18 Cycles): Positive
|
54.9 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
MP (18 Cycles): Negative
|
45.1 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
6 Months FU: Positive
|
63.6 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
6 Months FU: Negative
|
36.4 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
12 Months FU: Positive
|
60.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
12 Months FU: Negative
|
40.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
18 Months FU: Positive
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
18 Months FU: Negative
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
24 Months FU: Positive
|
59.3 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
24 Months FU: Negative
|
40.7 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
30 Months FU: Positive
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
30 Months FU: Negative
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
36 Months FU: Positive
|
57.1 Percentage of Participants
|
|
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
36 Months FU: Negative
|
42.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36Population: ITT Population. Here, 'Number Analyzed' signifies participants who were evaluable for indicated category.
Percentages of participants with IgH rearrangement during the Induction Phase, Maintenance Phase, and Follow-Up were reported.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=84 Participants
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
Post-IP
|
36.2 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
MP (9 Cycles)
|
37.1 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
MP (12 Cycles)
|
20.0 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
MP (15 Cycles)
|
29.4 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
MP (18 Cycles)
|
33.3 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
6 Months FU
|
100.0 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
12 Months FU
|
37.9 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
18 Months FU
|
50.0 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
24 Months FU
|
33.3 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
30 Months FU
|
0.0 Percentage of Participants
|
|
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
36 Months FU
|
45.8 Percentage of Participants
|
Adverse Events
Rituximab + Fludarabine + Cyclophosphamide
Serious events: 35 serious events
Other events: 82 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=86 participants at risk
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Vascular disorders
Capillary leak syndrome
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Anaemia
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.3%
8/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Cardiac disorders
Myocardial infarction
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Crohn's disease
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Malabsorption
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
Chest pain
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
General physical health deterioration
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
Pyrexia
|
7.0%
6/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Hepatobiliary disorders
Hepatic mass
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Immune system disorders
Cytokine release syndrome
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Gastroenteritis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Influenza
|
2.3%
2/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Meningitis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Pharyngitis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Pneumonia
|
8.1%
7/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Respiratory tract infection
|
2.3%
2/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Sinusitis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Viral myocarditis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic neuroma
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Syncope
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Renal and urinary disorders
Renal failure
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary sarcoidosis
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Surgical and medical procedures
Vertebroplasty
|
1.2%
1/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=86 participants at risk
Participants received rituximab 375 mg/m\^2 as IV infusion on Day 0 of Cycle 1 and 500 mg/m\^2 as IV infusion on Day 1 of Cycles 2-6 (cycle length = 28 days); fludarabine 25 mg/m\^2 on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 on Days 1-3 of each cycle during the Induction Phase. Participants with a PR or CR and appropriate neutrophil conditions received maintenance treatment with rituximab (375 mg/m\^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6 of Induction Phase.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
17.4%
15/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
27.9%
24/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Neutropenia
|
60.5%
52/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
20.9%
18/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
7.0%
6/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
18.6%
16/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
30.2%
26/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
17.4%
15/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
Asthenia
|
16.3%
14/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
Chills
|
7.0%
6/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
General disorders
Pyrexia
|
36.0%
31/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
31.4%
27/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Pneumonia
|
8.1%
7/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Respiratory tract infection
|
16.3%
14/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.1%
7/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
9.3%
8/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.8%
5/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.1%
7/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.8%
5/86 • Baseline through end of Follow-Up (up to 92 months)
Safety Population included all participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER