Clinical Trial Results:
Multicentre, Non-Randomised, Open-Label Phase II Study to Evaluate the Efficacy and Safety of Induction Treatment With Rituximab, Fludarabine, Cyclophosphamide, Followed by Rituximab Maintenance Therapy (R-Fc-Rm) in the First Lline Treatment of Chronic Lymphocytic Leukaemia
|
Summary
|
|
EudraCT number |
2007-002733-36 |
Trial protocol |
ES |
Global end of trial date |
20 May 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
31 May 2017
|
First version publication date |
31 May 2017
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ML21135
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00545714 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
F. Hoffmann-La Roche AG, Roche Trial Information Hotline, 41 61 6878333, global.trial_information@roche.com
|
||
Scientific contact |
F. Hoffmann-La Roche AG, Roche Trial Information Hotline, 41 61 6878333, global.trial_information@roche.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
28 Nov 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 May 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
This single arm study assessed the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with chronic lymphocytic leukemia (CLL).
|
||
Protection of trial subjects |
Investigators ensured that this study was conducted in full compliance with the principles of the last version of the Declaration of Helsinki and with the law and regulations of the country where the research was conducted, whichever provided greater protection to the study participants. The study fully complied with the principles stated in the “Good Clinical Practice Standards” of the International Council for Harmonisation (ICH) Tripartite Guideline (January 1997) and with all local regulations on clinical trials (Directive 2001/20/EC of the European Union and RD 223/2004).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Nov 2007
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
46 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 86
|
||
Worldwide total number of subjects |
86
|
||
EEA total number of subjects |
86
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
69
|
||
From 65 to 84 years |
17
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||
Recruitment details |
Of the 86 participants treated, demographic data were available for only 84 participants, and therefore, the 2 remaining participants have been counted under 'Adults (18-64 years)' in the preceding table. | ||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||
Screening details |
A total of 86 participants were enrolled in 29 centers in Spain in this two-phase study (Induction Phase and Maintenance Phase). | ||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||
Period 1 title |
Induction Phase (6 Months)
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
|
Arm title
|
Rituximab + Fludarabine + Cyclophosphamide | ||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Rituximab
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
MabThera
|
||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Participants received rituximab 375 mg/m^2 on Day 0 of Cycle 1 and 500 mg/m^2 on Day 1 of Cycles 2-6 (cycle length = 28 days) as IV infusion during the Induction Phase. Participants with 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.
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
Period 2
|
|||||||||||||||||||||
Period 2 title |
Maintenance Phase (36 Months)
|
||||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
|
Arm title
|
Rituximab + Fludarabine + Cyclophosphamide | ||||||||||||||||||||
Arm description |
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 (1 cycle = 28 days); fludarabine 25 mg/m^2 on Days 1 to 3 of each cycle and cyclophosphamide 250 mg/m^2 on Days 1 to 3 of each cycle during the induction phase. Participants with a partial or complete response (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. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Rituximab
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
MabThera
|
||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
||||||||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||||||||
Dosage and administration details |
Participants received rituximab 375 mg/m^2 on Day 0 of Cycle 1 and 500 mg/m^2 on Day 1 of Cycles 2-6 (cycle length = 28 days) as IV infusion during the Induction Phase. Participants with 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.
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Induction Phase (6 Months)
|
|||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Rituximab + Fludarabine + Cyclophosphamide
|
||
Reporting group description |
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. | ||
Reporting group title |
Rituximab + Fludarabine + Cyclophosphamide
|
||
Reporting group description |
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 (1 cycle = 28 days); fludarabine 25 mg/m^2 on Days 1 to 3 of each cycle and cyclophosphamide 250 mg/m^2 on Days 1 to 3 of each cycle during the induction phase. Participants with a partial or complete response (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. | ||
Subject analysis set title |
Rituximab + Fludarabine + Cyclophosphamide
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
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.
|
||
Subject analysis set title |
Rituximab + Fludarabine + Cyclophosphamide
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
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.
|
||
|
|||||||||
End point title |
Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen [1] | ||||||||
End point description |
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. ITT Population included participants who received at least one dose of study drug and met inclusion/exclusion criteria.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 9
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No inferential analysis was performed. Only descriptive summaries were planned. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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. ITT Population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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, 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [2] - Here, 'n' signifies participants who were evaluable for indicated category. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Clinical Response of CR or PR Among Participants with Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry | ||||||||||||||||||||||||||||||
End point description |
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 Maintenance Phase and Follow-Up.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point 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, 36
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| Notes [3] - ITT Population. Those with negative MRD evaluable, where 'n' signifies those evaluable for category. |
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||
End point title |
Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi) | ||||||||
End point description |
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. ITT Population.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival (OS) | ||||||||
End point description |
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. ITT Population.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to death due to any cause (up to 92 months)
|
||||||||
|
|||||||||
| Notes [4] - 99999 = upper limit not estimable due to high number of censored participants. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression-Free Survival (PFS) | ||||||||
End point description |
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 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. ITT Population.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
|
||||||||
|
|||||||||
| Notes [5] - 99999 = upper limit not estimable due to high number of censored participants. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants Who Died | ||||||||
End point description |
Safety Population included all participants who received at least one dose of study drug.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to death due to any cause (up to 92 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Treatment-Free Survival (TFS) | ||||||||
End point description |
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. ITT Population. Only those who received new chemotherapy/immunotherapy, as per definitions for TFS, were included in the analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Duration of Response (DOR) | ||||||||
End point description |
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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)
|
||||||||
|
|||||||||
| Notes [6] - ITT Population. Those with CR/PR were evaluable. 99999 = not estimable due to high number censored. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood | ||||||||||||||||||||||||||||||
End point description |
Percentages of participants with CD38 expression by >/=30% of CLL cells during the Induction Phase, Maintenance Phase, and Follow-Up were reported. ITT Population.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point 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, 36
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| Notes [7] - Here, 'n' signifies participants who were evaluable for indicated category. |
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Genetic Abnormalities | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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. ITT Population. Designation of 'MP (xC)' refers to number of cycles in Maintenance Phase.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [8] - Here, 'n' signifies participants who were evaluable for indicated category. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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. ITT Population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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, 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [9] - Here, 'n' signifies participants who were evaluable for indicated category. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement | ||||||||||||||||||||||||||||||
End point description |
Percentages of participants with IgH rearrangement during the Induction Phase, Maintenance Phase, and Follow-Up were reported. ITT Population.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point 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, 36
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| Notes [10] - Here, 'n' signifies participants who were evaluable for indicated category. |
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||
End point title |
Percentage of Participants With PD or Death | ||||||||
End point description |
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. ITT Population.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline through end of Follow-Up (up to 92 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety Population included all participants who received at least one dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rituximab + Fludarabine + Cyclophosphamide
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
