Clinical Trial Results:
STUDY OF THE EFFICACY AND SAFETY OF FIRST LINE TREATMENT
WITH CHOP AND LENALIDOMIDE (Rev-CHOP) IN PATIENTS AGED
FROM 60 TO 80 YEARS WITH PREVIOUSLY UNTREATED
ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA (AITL).
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Summary
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EudraCT number |
2011-001356-10 |
Trial protocol |
BE |
Global end of trial date |
21 Mar 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Feb 2021
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First version publication date |
25 Feb 2021
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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 |
Revail
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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 |
LYSARC
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Sponsor organisation address |
CH LYON SUD BATIMENT 2D, PIERRE BENITE, France, 69495
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Public contact |
Project Manager, LYSARC, +33 (0)472669333, revail@lysarc.org
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Scientific contact |
Project Manager, LYSARC, +33 (0)472669333, revail@lysarc.org
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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 |
21 Mar 2019
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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 |
21 Mar 2019
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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 the study is to evaluate the Complete Metabolic Response (CMR) rate at the end of treatment.
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Protection of trial subjects |
patient could receive salvage treatment
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Background therapy |
CHOP : cyclophosphamide - prednisone- doxorubicine - vincristine | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Nov 2011
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Long term follow-up planned |
No
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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 |
Belgium: 3
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Country: Number of subjects enrolled |
France: 77
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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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) |
15
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From 65 to 84 years |
65
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85 years and over |
0
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Recruitment
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Recruitment details |
France: first recruitment: 28NOV2011 and last recruitment: 09MAR2017 Belgium: first recruitment: 25AUG2015 and last recruitment: 14FEB2017 | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
no previous therapy; histologically proven T-cell angioimmunoblastic lymphoma (AITL) 80 patients are included | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Baseline
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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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Experimental | ||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lenalidomide
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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 |
25mg D1 to D4 - 8 cycles of 21 days
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Period 2
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Period 2 title |
Treatment
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||
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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Experimental | ||||||||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lenalidomide
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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 |
25mg D1 to D4 - 8 cycles of 21 days
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Efficacy set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The efficacy set includes evaluable patients.
Evaluable patients are defined as all patients who received at least one cycle of Rev-CHOP:
- with complete treatment and with central review of PET scans at baseline and at the end of treatment
- or prematurely withdrawn before C8
This population will be used for all efficacy analyses.
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Subject analysis set title |
AITL/TFH set
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects who received at least one dose of Lenalidomide and one cycle of CHOP and had a confirmed diagnosis of AITL or nodal PTCL with a TFH phenotype. These subjects were included in the sensitivity analysis.
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End points reporting groups
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Reporting group title |
Experimental
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Reporting group description |
- | ||
Reporting group title |
Experimental
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Reporting group description |
- | ||
Subject analysis set title |
Efficacy set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The efficacy set includes evaluable patients.
Evaluable patients are defined as all patients who received at least one cycle of Rev-CHOP:
- with complete treatment and with central review of PET scans at baseline and at the end of treatment
- or prematurely withdrawn before C8
This population will be used for all efficacy analyses.
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Subject analysis set title |
AITL/TFH set
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received at least one dose of Lenalidomide and one cycle of CHOP and had a confirmed diagnosis of AITL or nodal PTCL with a TFH phenotype. These subjects were included in the sensitivity analysis.
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End point title |
Complete Metabolic Response at end of treatment based on central review [1] | ||||||||
End point description |
The primary endpoint is the Complete Metabolic Response (CMR) rate at the end of treatment according to Lugano classification and based on PET scan independent central review.
Response are assessed after completion of treatment if all planned cycles were delivered or at withdrawal.
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End point type |
Primary
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End point timeframe |
At end of treatment, i.e. after complete treatment or at treatment discontinuation
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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: The conclusion of the trial is based on the confidence interval related to the primary criterion. This interval is compared to the proportion of respondors at end of treatmentaccording to the null hypothesis : 0.45. There is no arm comparison. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Complete Response (CR) rate according to Cheson 2007 criteria based on investigator evaluation | ||||||||
End point description |
Complete Response (CR) rate according to Cheson 2007 criteria based on investigator evaluation of PET scan will be used as secondary endpoint. Patient without response assessment (due to whatever reason) will be considered as non-responder.
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End point type |
Secondary
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End point timeframe |
At end of treatment, i.e. after completed treatment or at premature treatment discontinuation
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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 |
Progression-Free Survival (PFS) is measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause, whichever occurs first.
Responding patients and patients who are lost to follow up are censored at their last tumor assessment date.
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End point type |
Secondary
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End point timeframe |
2-year PFS
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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 (OS) is measured from the date of inclusion to the date of death from any cause.
Patients alive are censored at their last follow-up date. Patients who are alive or lost to follow-up at the time of analysis are censored at the date of the last contact.
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End point type |
Secondary
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End point timeframe |
2-year OS
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| No statistical analyses for this end point | |||||||||
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End point title |
Event-Free Survival (EFS) | ||||||||
End point description |
Event-Free survival (EFS) is measured from the date of inclusion to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause.
Responding patients and patients who are lost to follow up are censored at their last tumor assessment date.
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End point type |
Secondary
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End point timeframe |
2-year EFS
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| No statistical analyses for this end point | |||||||||
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End point title |
Sensitivity analysis of complete Metabolic Response at end of treatment based on central review | ||||||||
End point description |
Complete Metabolic Response (CMR) rate at the end of treatment according to Lugano classification and based on PET scan independent central review on subject with confirmed diagnosis (AITL/TFH set).
Response are assessed after completion of treatment if all planned cycles were delivered or at withdrawal.
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End point type |
Post-hoc
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End point timeframe |
At end of treatment, i.e. after complete treatment or at treatment discontinuation
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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 |
From informed consent up to 30 days after the last study drug
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Adverse event reporting additional description |
All adverse events of intensity grade ≥ 2 regardless of relationship to Revlimid that occurred after the informed consent up to 30 days after the last study drug administration are recorded.
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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 |
4.03
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Reporting groups
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Reporting group title |
Safety set
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Reporting group description |
The safety set includes all patients who have received at least one dose of Revlimid (lenalidomide). The safety set is used for all safety analyses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Jan 2012 |
• Precision regarding prophylaxis treatment, that all subjects will be required to take a low molecular weight heparin as thromboembolic event prophylaxis during study period.
• Modification of non-inclusion criteria n°9 to add that any history of malignancy, other than that treated in this research, unless the subject has remained free of the disease for over 5 years
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20 Feb 2015 |
• Modification of the study duration from 42 months to 78 months and date of the end of study due to recruitment slower than expected |
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18 Mar 2016 |
• Modification of the primary objective to become the CMR according to Lugano Classification.
• The CRR according to Cheson 2007 becomes a secondary objective.
• Adding in appendix of Lugano 2014 criteria
• Clarification of the term “withdraw” which means withdraw of study treatment but does not exclude from follow-up period.
• Precision on the adverse event and serious adverse event reporting such as adverse events will not recorded after the start of a new chemotherapy treatment or after lymphoma progression, except if considered related to study treatment.
• Update of the Lenalidomide Pregnancy Prevention Plan
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27 Feb 2017 |
• Adding of biological studies
• Precision on progression criteria not-based only on CT-Scan, it should be based on CT scan or relevant clinical data, exams (e.g. PET-Scan).
• Precision on follow-up period, thus subjects will be followed 18 months after the last subject included has completed the treatment.
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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 | |||
