Clinical Trial Results:
A phase II multicenter open-label study of MabThera (Rituximab) addition to regularly prescribed chemotherapy in patients with untreated Mantle Cell Lymphoma
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Summary
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EudraCT number |
2009-011433-27 |
Trial protocol |
RO |
Global end of trial date |
19 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
17 May 2017
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First version publication date |
17 May 2017
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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 |
ML22489
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01144403 | ||
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, CH4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, 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 |
19 Aug 2014
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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 |
19 Aug 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine Overall Response Rate (ORR) (expressed as complete response [CR] and partial response [PR]) in Mantle Cell Lymphoma (MCL) subjects treated with MabThera plus chemotherapy. The percentage of subjects who achieve CR/ unconfirmed complete (CRu) or PR while on rituximab induction therapy will be assessed.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Jun 2010
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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 |
24 Months | ||
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 |
Romania: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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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) |
7
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
A total 8 subjects were enrolled from Romania. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (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, 375 milligram per metre square (mg/m^2) was given intravenously on Day 1 and then every 28 days (+/7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles). Cyclophosphamide: as prescribed, 6 cycles Fludarabine: as prescribed, 6 cycles Mitoxantrone: as prescribed, 6 cycles Rituximab [Mabthera/Rituxan]: 375 mg/m^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Rituximab
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Investigational medicinal product code |
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Other name |
Mabthera, Rituxan
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Rituximab 375 mg/m^2 was administered intravenously, Day 1 of each 28-day cycle, up to 8 cycles.
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Baseline characteristics reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab, 375 milligram per metre square (mg/m^2) was given intravenously on Day 1 and then every 28 days (+/7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles). Cyclophosphamide: as prescribed, 6 cycles Fludarabine: as prescribed, 6 cycles Mitoxantrone: as prescribed, 6 cycles Rituximab [Mabthera/Rituxan]: 375 mg/m^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab, 375 milligram per metre square (mg/m^2) was given intravenously on Day 1 and then every 28 days (+/7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles). Cyclophosphamide: as prescribed, 6 cycles Fludarabine: as prescribed, 6 cycles Mitoxantrone: as prescribed, 6 cycles Rituximab [Mabthera/Rituxan]: 375 mg/m^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles. | ||
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End point title |
Overall Response Rate (ORR) [1] | ||||||||
End point description |
Overall Response Rate (ORR) was determined by tumor response according to International Workshop Group to Standardize Response Criteria for mantle cell lymphoma (MCL) criteria from confirmed evaluations of both target, radiographically evaluated, and non-target lesions. A responder is defined as a subject experiencing either a complete (CR)/ unconfirmed complete (Cru), or partial response (PR) by these criteria. As per criteria; CR = disappearance of all evidence of disease; CRu = the sum of the product of the diameters (SPD) of multiple nodes decreased by at least 75%; PR = regression of measurable disease and no new sites. Efficacy population included all the subjects who had received at least one dose of study treatment.
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End point type |
Primary
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End point timeframe |
Up to 50 months (approximately)
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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: Only descriptive data was planned to be reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
Overall survival is defined as time from date of enrollment to the date of death, regardless of the cause of death. Efficacy population included all the subjects who had received at least one dose of study treatment.
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End point type |
Secondary
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End point timeframe |
From the time of enrollment until death due to any cause (up to 50 months [approximately])
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival (PFS) | ||||||||
End point description |
PFS is defined as the interval between the day of enrollment and the first documentation of progressive disease or death. Progression of disease is defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Efficacy population included all the subjects who had received at least one dose of study treatment.
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End point type |
Secondary
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End point timeframe |
From the time of enrollment until death due to any cause (up to 50 months [approximately])
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subject With Adverse Event (AE) | ||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment. Safety population included all the subjects who had received at least one dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to 50 months (approximately)
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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 approximately 50 months
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Adverse event reporting additional description |
Safety population included all the subjects who had received at least one dose of study treatment.
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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 |
14.0
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Reporting groups
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Reporting group title |
Rituximab
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Reporting group description |
Rituximab, 375 milligram per metre square (mg/m^2) was given intravenously on Day 1 and then every 28 days (+/7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles). Cyclophosphamide: as prescribed, 6 cycles Fludarabine: as prescribed, 6 cycles Mitoxantrone: as prescribed, 6 cycles Rituximab [Mabthera/Rituxan]: 375 mg/m^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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11 Jul 2010 |
Added 6 new sites and 6 new investigators to the study. |
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06 Jun 2011 |
Protocol version 2.0/14.09.2010 |
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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. | |||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. The study was prematurely terminated with 8 subjects enrolled, all of them were included into the statistical analyses. | |||
