Clinical Trial Results:
Randomized phase II Trial comparing Lenalidomide with lowdose dexamethasone versus Lenalidomide in
Second Line Multiple Myeloma (MM)
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Summary
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EudraCT number |
2010-021857-38 |
Trial protocol |
SE DK |
Global end of trial date |
20 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jan 2020
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First version publication date |
11 Jan 2020
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Other versions |
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Summary report(s) |
summary |
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 |
PI-RV-MM-10-07
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Karolinska univ. hospital
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Sponsor organisation address |
141 86, Stockholm, Sweden,
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Public contact |
Hareth Nahi, Karolinska universe. hospital, +46 737121465, hareth.nahi@sll.se
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Scientific contact |
Hareth Nahi, Karolinska Inst, +46 737121465, hareth.nahi@sll.se
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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 |
10 Jan 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Nov 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2015
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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 |
To assess efficacy (TTP) of maintenance treatment with lenalidomide alone compared to a regimen with
lenalidomide and low dose dexamethasone
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Protection of trial subjects |
Subjects were be fully informed of the risks and requirements of the study and, during the study, subjects were given any new information that may affect their decision to continue participation. They were told that their consent to participate in the study is voluntary and may be withdrawn at any time with no reason given and without penalty or loss of benefits to which they would otherwise be entitled. Only subjects who were fully able to understand the risks, benefits, and potential adverse events of the study, and provide their consent voluntarily will be enrolled.
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Background therapy |
In order to achieve a response of best possible quality as soon as possible the combination of lenalidomide and dexamethasone works synergistically to reduce the tumor burden by several mechanisms adding up to a fast tumoricidal effect. | ||
Evidence for comparator |
The mechanism of action of lenalidomide has a duality of effects: it directly leads to tumour cell death and improves the immune system to keep the tumour in remission (Chanan-Khan 2008). When combined with dexamethasone, lenalidomide therapy provides sustained control of multiple myeloma in relapsed/refractory patients who have received at least one prior therapy (San M 2009). Unlike chemotherapy, lenalidomide stimulates the immune response while also demonstrating tumoricidal activity (ChananKhan 2008, Schütt 2006). Additionally lenalidomide has a well-characterized safety profile, even with longer-term use (San Miguel JF et al. Haematologica. 2009 ) | ||
Actual start date of recruitment |
01 Mar 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 |
Norway: 9
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Country: Number of subjects enrolled |
Sweden: 47
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Country: Number of subjects enrolled |
Denmark: 6
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Worldwide total number of subjects |
62
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EEA total number of subjects |
62
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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) |
52
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From 65 to 84 years |
8
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85 years and over |
2
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Recruitment
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Recruitment details |
Patients who are in at least PR and have received lenalidomide as 2nd line treatment for MM will were recruited. | |||||||||
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Pre-assignment
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Screening details |
A written informed consent must be obtained before any study-specific screening procedures are performed. | |||||||||
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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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Len/dex | |||||||||
Arm description |
treatment with Lenalidomide and dexamethasone | |||||||||
Arm type |
standard | |||||||||
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 |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
P.O. 25mg
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Arm title
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Lenalidomide | |||||||||
Arm description |
Treatment with Lenalidomide only | |||||||||
Arm type |
study arm | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Len/dex
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Reporting group description |
treatment with Lenalidomide and dexamethasone | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lenalidomide
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Reporting group description |
Treatment with Lenalidomide only | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Len/dex
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Reporting group description |
treatment with Lenalidomide and dexamethasone | ||
Reporting group title |
Lenalidomide
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Reporting group description |
Treatment with Lenalidomide only | ||
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End point title |
TTP | ||||||||||||
End point description |
After 26 months’ median follow-up, median TTP was 24·9 months (12·5–not calculable) versus not reached with Len versus Len+Dex
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End point type |
Primary
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End point timeframe |
From randomisation until 24m from the last patient randomised
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| Notes [1] - The actual value is nor reached |
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Statistical analysis title |
methods | ||||||||||||
Statistical analysis description |
Graphs were generated and statistical analyses performed by GraphPad Prism (GraphPad Software Inc. La Jolla, CA, USA) and FlowJo X software (TreeStar Inc. OR, USA).
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Comparison groups |
Lenalidomide v Len/dex
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Number of subjects included in analysis |
62
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | ||||||||||||
P-value |
= 1 [3] | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Confidence interval |
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| Notes [2] - comparison between len and len/dex [3] - <0.05 |
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Adverse events information
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Timeframe for reporting adverse events |
From signed inform consent until end of the trail
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Adverse event reporting additional description |
. The most common haematologic TEAEs during the observational study were thrombocytopenia (38%), anaemia (30%), and neutropenia (13%). Febrile neutropenia was reported in only 2% of the observational study population. Upper respiratory tract infection was the most common non-haematologic TEAE (15%). Thromboembolic events occurred in seven patients
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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 |
2
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Reporting groups
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Reporting group title |
Fatigue
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Reporting group description |
standard arm | ||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
