Clinical Trial Results:
A multicenter, phase III, open-label study evaluating the benefit of a long-term MabThera® (rituximab) maintenance therapy in patients with advanced follicular lymphoma after induction of response (CR(u) or PR) with MabThera® (rituximab) containing first-line regimen
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Summary
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EudraCT number |
2005-000359-13 |
Trial protocol |
HU |
Global end of trial date |
12 Aug 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Mar 2016
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First version publication date |
18 Mar 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ML18167
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH‐4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Aug 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Aug 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluation of the efficacy and safety of a long-term MabThera® (rituximab) maintenance therapy in patients with advanced follicular lymphoma after induction of response (CR(u) or PR) with a MabThera® (rituximab) containing first-line regimen.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all participants and/or their legally authorized representative. Participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
08 Jul 2005
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
3 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Hungary: 124
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Worldwide total number of subjects |
124
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EEA total number of subjects |
124
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
102
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted between 08 July 2005 to 12 Aug 2013 at 15 sites in Hungary. | ||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total number of 124 patients were recruited. Of these, 83 patients completed the maintenance therapy with rituximab(MabThera) and entered the 3-year follow-up phase. Of these, 69 patients completed the follow-up phase. | ||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
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Arms
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Arm title
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Rituximab | ||||||||||||||||||||||||||
Arm description |
Rituximab was administered by intravenous infusion every 8 weeks at a dose of 375 mg/m2. | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
All patients received 12 cycles of 375 mg/m2 of MabThera (every 8 weeks) as a treatment.
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Baseline characteristics reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab was administered by intravenous infusion every 8 weeks at a dose of 375 mg/m2. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab was administered by intravenous infusion every 8 weeks at a dose of 375 mg/m2. | ||
Subject analysis set title |
ITT (intend-to-treat) population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Patients who received at least one maintenance rituximab infusion, excluding non-eligible patients according to protocol.
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End point title |
Event-free survival [1] | ||||||||
End point description |
Event-free survival (EFS) was defined as the time from baseline (Week 0) to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first. Mean EFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population (patients who received at least one maintenance rituximab infusion) was used for this analysis.
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End point type |
Primary
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End point timeframe |
From randomization to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first, assessed up to 5 years
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| 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: Mean EFS was estimated by the Kaplan-Meier estimation and 95% confidence interval has been presented in the results section. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Adverse Events | ||||||||||
End point description |
An adverse event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, requires intervention to prevent permanent impairment or damage, or results in death. Safety population (participants who received at least one dose of study medication and had safety data after the first dose of study drug) was used for this analysis.
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End point type |
Secondary
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End point timeframe |
Up to 27 months
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End point title |
Overall Survival | ||||||||
End point description |
Overall survival, defined as the time between baseline (Week 0) and the date of death irrespective of the cause of death. Mean OS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
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End point type |
Secondary
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End point timeframe |
From randomization until death, assessed up to 5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to progression | ||||||||
End point description |
Time to progression (TTP) defined as time from baseline to disease progression or relapse, death from the follicular lymphoma or institution of a new regimen because of the follicular lymphoma. Mean TTP was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
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End point type |
Secondary
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End point timeframe |
From baseline (Week 0) to disease progression, relapse, death from the follicular lymphoma or institution of a new regimen, whichever occurs first, assessed up to 5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to new anti-lymphoma treatment | ||||||||
End point description |
Time to next anti-lymphoma treatment (TTNLT) defined as time from baseline to institution of a new antilymphoma regimen (including chemo‐, radio‐ or immunotherapies). Mean TTNLT was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
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End point type |
Secondary
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End point timeframe |
From baseline (Week 0) to institution of a new antilymphoma regimen, assessed up to 5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of response | ||||||||
End point description |
Duration of Response (DR) defined as time from first documented response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DR was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
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End point type |
Secondary
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End point timeframe |
From first documented response to induction treatment to relapse or progression or death, assessed up to 5 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease-free survival | ||||||||
End point description |
Disease-free survival (DFS) being defined as time from first documented complete response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
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End point type |
Secondary
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End point timeframe |
From first documented complete response to induction treatment to relapse or progression or death, whichever occurs first, assessed up to 5 years
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 3 months after last study drug administration
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab was administered by intravenous infusion every 8 weeks at a dose of 375 mg/m2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 Mar 2007 |
Additional requirements were added regarding the eligibility screening process. The number of sites were modified to 18. Urine pregnancy test was added to the required assessment during the maintenance therapy cycle. Appendix I was added to the protocol (Calculation of FLIPI score). Appendix J was added to the protocol (Eligibility fax form). |
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20 Jan 2010 |
Interim analysis was added to the protocol. Time of publication of the IA was clarified. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
