Clinical Trial Results:
A randomised evaluation of molecular guided therapy for diffuse large B-cell lymphoma with Bortezomib
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Summary
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EudraCT number |
2010-022422-32 |
Trial protocol |
GB |
Global end of trial date |
31 Aug 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
24 May 2025
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First version publication date |
24 May 2025
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Other versions |
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Summary report(s) |
Primary results Final results |
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 |
RHMCAN0749
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Additional study identifiers
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ISRCTN number |
ISRCTN51837425 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Hospital Southampton NHS Foundation Trust
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Sponsor organisation address |
University Road, Highfield, Southampton, United Kingdom, SO17 1BJ
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Public contact |
Louise Stanton, University Hospital Southampton NHS Foundation Trust, l.stanton@soton.ac.uk
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Scientific contact |
Louise Stanton, University Hospital Southampton NHS Foundation Trust, l.stanton@soton.ac.uk
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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 |
30 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2021
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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 |
The primary objective of this trial is to demonstrate the efectiveness of bortezomib in combination with rituximab and CHOP chemotherapy (RB-CHOP) in comparison R-CHOP alone for the treatment of previously untreated patients with diffuse large B cell lymphoma. Efficacy will be determined by the number of patients who are alive and there condition has not progressed (Progression Free Survival). The study also will assess if the molecular profile (phenotype) (either ABC or GCB) determines the benefit from the addition of bortezomib.
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Protection of trial subjects |
none
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Background therapy |
none | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Jun 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United Kingdom: 1076
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Worldwide total number of subjects |
1076
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EEA total number of subjects |
0
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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) |
546
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From 65 to 84 years |
528
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85 years and over |
2
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Recruitment
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Recruitment details |
Between June 2, 2011, and June 10, 2015, 1128 eligible patients were registered, of whom 918 (81%) were randomly assigned to receive treatment. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Some patients with lymphoma with poor prognostic features at the presentation need to be excluded from such trials on the grounds of performance status or the need for urgent treatment before screening procedures can be completed. | ||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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R-CHOP | ||||||||||||||||||
Arm description |
All study patients will receive 1 cycle of conventional R-CHOP chemotherapy on a standard 21 day schedule. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
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 |
Day 1
375mg/m2
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Investigational medicinal product name |
Cyclophosphamide
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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 |
Day 1
750mg/m2
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Investigational medicinal product name |
Doxorubicin
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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 |
Day 1
50mg/m2
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Investigational medicinal product name |
Vincristine
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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 |
Day 1
1.4mg/m2 (max 2mg)
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Day 1-5
100mg, once a day
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Arm title
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RB-CHOP | ||||||||||||||||||
Arm description |
Patients in this arm will receive 5 cycles of R-CHOP with bortezomib according to the schedule below | ||||||||||||||||||
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 |
Day 1
375mg/m2
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Investigational medicinal product name |
Bortezomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Day 1 and Day 8
1.6 mg/m2
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Investigational medicinal product name |
Cyclophosphamide
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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 |
Day 1
750mg/m2
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Investigational medicinal product name |
Doxorubicin
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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 |
Day 1
50mg/m2
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Investigational medicinal product name |
Vincristine
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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 |
Day 1
1.4mg/m2 (max 2mg)
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Day 1-5
100mg, once a day
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Baseline characteristics reporting groups
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Reporting group title |
R-CHOP
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Reporting group description |
All study patients will receive 1 cycle of conventional R-CHOP chemotherapy on a standard 21 day schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
RB-CHOP
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Reporting group description |
Patients in this arm will receive 5 cycles of R-CHOP with bortezomib according to the schedule below | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
R-CHOP
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Reporting group description |
All study patients will receive 1 cycle of conventional R-CHOP chemotherapy on a standard 21 day schedule. | ||
Reporting group title |
RB-CHOP
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Reporting group description |
Patients in this arm will receive 5 cycles of R-CHOP with bortezomib according to the schedule below | ||
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End point title |
progression-free survival events | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30 months
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Statistical analysis title |
30-month progression-free survival | |||||||||
Comparison groups |
R-CHOP v RB-CHOP
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Number of subjects included in analysis |
719
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
> 0.05 | |||||||||
Method |
Kaplan-Meier estimate | |||||||||
Confidence interval |
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Statistical analysis title |
progression- free survival combined activation | |||||||||
Statistical analysis description |
progression-free survival in the combined activated and germinal center B-cell populations
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Comparison groups |
R-CHOP v RB-CHOP
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Number of subjects included in analysis |
719
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.23 | |||||||||
Method |
Kaplan-Meier estimate | |||||||||
Confidence interval |
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Statistical analysis title |
progression-free survival in mITT population | |||||||||
Statistical analysis description |
30-month progression-free survival in the mITT population
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Comparison groups |
R-CHOP v RB-CHOP
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Number of subjects included in analysis |
719
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.16 | |||||||||
Method |
Kaplan-Meier estimate | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
The reporting requirement for SAEs and AEs affecting patients applies for all events occurring up to 30 days after the last administration of study drugs. For details of adverse events see the attached PDF results papers.
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Adverse event reporting additional description |
All unresolved adverse events should be followed by the investigator until resolved, the patient is lost to follow-up, or the adverse
event is otherwise explained. At the last scheduled visit, the investigator should instruct each patient to report any subsequent event(s) that the patient believes might related.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
Free text AEs & SAEs | ||
Dictionary version |
N/A
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There are no detailed adverse events provided as these were not coded to MEDRA but categorised based on free text. For details of the adverse and serious events experienced by patients in the study please see the PubMed web links and associated appendices and the attached PDFs. For details of all other endpoints too also see the attached PDF and web links. |
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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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25 Jan 2011 |
Protocol version2, 11 sites added |
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20 Apr 2011 |
Protocol version 3 - Updates to Patient Information Sheet, Informed Consent Form and Protocol |
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06 Sep 2011 |
Protocol version 3 - Removal of named suppliers for study medication so local suppliers can be used |
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10 Apr 2012 |
Protocol version 4 – Changes to study drug labels |
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24 May 2012 |
Protocol version 5 – Addition of sites in Switzerland and updated Investigational Brochure for Bortezomib |
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13 May 2013 |
Protocol version 6 – PIS and ICF updated to include information about data being used for research purposes |
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28 Mar 2014 |
Protocol version 7 - Dosage regimen/duration of treatment Bortezomib now being given sub cutaneous and at an increased dose of1.6mg/ m2;Schedule of observations and procedures. Sites must have results for Hep B prior to registration and 12 lead ECG should be performed on all patients; PET/CT hybrid scanners may be used if scanner is of diagnostic quality and includes the use of IV contrast; Justification of switch from IV to SC for administration of Bortezomib statement; clarifications on various sections of the protocol |
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02 Oct 2014 |
Protocol version 8 – Sample size increased to 1,132 |
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07 Apr 2016 |
Protocol version 9 - Update of IB (Ed 18). Clarification of analysis timepoints. Addition of a table, which holds all relevant IB and SmPC versions. Notification of sites to be closed: Queen Elizabeth Hospital Gateshead (Dr S Marshall) and Mid Staffordshire(Dr P Revell). |
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17 Jan 2019 |
Protocol version 10 - Clarification on analysis time points and updated SmPCs, PIS & ICF v.7 - data storage clairifcation now Rave on US server. |
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17 Aug 2021 |
Protocol version 11 - Change EOT definition to remove long term observational follow up - including new protocol. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30948276 http://www.ncbi.nlm.nih.gov/pubmed/36972491 |
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