Clinical Trial Results:
A randomised comparison of daily 25 mg versus 5 mg lenalidomide as maintenance therapy after high-dose therapy and autologous stem cell transplantation in patients with multiple myeloma.
|
Summary
|
|
EudraCT number |
2007-003945-33 |
Trial protocol |
DE |
Global end of trial date |
22 Jun 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
08 Oct 2020
|
First version publication date |
08 Oct 2020
|
Other versions |
|
Summary report(s) |
LenaMain Results Summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
RV-MM-PI-280
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00891384 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Gesellschaft für Medizinische Innovation –Hämatologie und Onkologie mbH (GMIHO)
|
||
Sponsor organisation address |
Almstadtstraße 7, Berlin, Germany, 10119
|
||
Public contact |
Medical Consulting, Gesellschaft für Medizinische Innovation –Hämatologie und Onkologie mbH (GMIHO), +49 35125933100, info@gmiho.de
|
||
Scientific contact |
Prof. Dr. Guido Kobbe, Department of Hematology, Oncology and Clinical Immunology
Heinrich-Heine-University, +49 211 8117720, Kobbe@med.uni-duesseldorf.de
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
16 Jun 2018
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
22 Jun 2017
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
22 Jun 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Compare the event-free survival (EFS) of patients with multiple myeloma who receive two different dose levels (25 vs. 5 mg daily) of lenalidomide as maintenance therapy after first line high-dose therapy and autologous stem cell transplantation.
|
||
Protection of trial subjects |
The conduct, evaluation, and documentation of this study, was in compliance with the Good Clinical Practice Guidelines and under the guiding principles detailed in the Declaration of Helsinki. The study was also be carried out in keeping with applicable local law(s) and regulation(s) as well as GDPR. All toxicities were monitored and patients who had rash, myelotoxicity of grade 2 or more, thrombo-embolic events of grade 2 or more, neuropathy of grade two or more, bradycardia of grade 3 or more, change in performance status, transfusion requirement, bleeding complications grade 3 or more and infections grade 3 or more were examined.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jun 2009
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 188
|
||
Worldwide total number of subjects |
188
|
||
EEA total number of subjects |
188
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
144
|
||
From 65 to 84 years |
44
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
The trial was conducted at 6 study sites in Germany. From 04 June 2009 until 01 February 2015 on a total of 194 patients were included. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
Inclusion of 194 patients was planned, and the analysis of the primary endpoint was planned to be done after at least 96 subjects have developed disease progression. 194 patients were included and 188 are eligible for the analysis of the primary endpoint as there were 6 screening failures. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Not blinded | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
No
|
|||||||||
|
Arm title
|
Arm A | |||||||||
Arm description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm A and received 25 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lenalidomide
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
Revlimid®
|
|||||||||
Pharmaceutical forms |
Capsule, hard
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
All patients started with consolidation therapy. Consolidation therapy consisted of 6 cycles of lenalidomide 25 mg daily for 21 days every 28 days. After consolidation therapy patients treated with 25 mg lenalidomide daily for 21 days every 28 days. Maintenance therapy was continued until disease progression occured or untolerable side effects occur despite of dose reduction or the study ends.
|
|||||||||
|
Arm title
|
Arm B | |||||||||
Arm description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm B and received 5 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lenalidomide
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
Revlimid®
|
|||||||||
Pharmaceutical forms |
Capsule, hard
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
All patients started with consolidation therapy. Consolidation therapy consisted of 6 cycles of lenalidomide 25 mg daily for 21 days every 28 days. After consolidation therapy patients treated with 5 mg lenalidomide daily for 21 days every 28 days. Maintenance therapy was continued until disease progression occured or untolerable side effects occur despite of dose reduction or the study ends.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm A and received 25 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm B and received 5 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Arm A
|
||
Reporting group description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm A and received 25 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | ||
Reporting group title |
Arm B
|
||
Reporting group description |
Oral lenalidomide was given on day 1 of cycle 1 of consolidation therapy at a dose of 25 mg daily for 21 days every 28 days. After 6 cycles of consolidation therapy patients were treated in Arm B and received 5 mg lenalidomide daily for 21 days every 28 days. Treatment was continued as tolerated until disease progression developed. | ||
|
||||||||||
End point title |
Event-free Survival (EFS) | |||||||||
End point description |
The primary efficacy endpoint was event-free survival (EFS) from the time point of randomisation, where death or progress counted as events.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
from randomisation until the 96th patient experienced relapse
|
|||||||||
|
||||||||||
Statistical analysis title |
Primary statistical analysis | |||||||||
Comparison groups |
Arm A v Arm B
|
|||||||||
Number of subjects included in analysis |
188
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.05 | |||||||||
Method |
Logrank | |||||||||
Confidence interval |
||||||||||
|
|||
|
Adverse events information [1]
|
|||
Timeframe for reporting adverse events |
from randomisation until experienced relapse
|
||
Assessment type |
Systematic | ||
|
Dictionary used for adverse event reporting
|
|||
Dictionary name |
MedDRA | ||
Dictionary version |
18.1
|
||
| Frequency threshold for reporting non-serious adverse events: 3% | |||
| 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: The majority of the AEs of a grade ≥ 3 were of the System Organ Class Blood/Bone Marrow, where the most common AEs of a grade ≥ 3 indicate a decrease in Neutrophils/granulocytes (ANC/AGC) or Leukocytes (total WBC) (graded according to the NCI CTCAE v3.0). The safety analysis indicated that in Arm A (25 mg lenalidomide daily) the number of patients with at least one adverse event (AE) of a grade ≥ 3 was higher than in Arm B (5 mg lenalidomide daily) (84 (87.5%) vs. 62 (64.58%). |
|||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Apr 2009 |
Protocol Version 20, 06.03.2009: Changing of Sponsor`s Address; MRT with contrast material |
||
12 Jul 2012 |
Protocol Version 21, 18.06.2012: Changing of Sponsor`s Address; changing of the manufacturing of Lenalidomide-> Bottles to blister
|
||
07 Nov 2012 |
Protocol Version 23, 02.10.2012: Different reasons of dosis reduction; recommendation on treatment of Infections; new study site
|
||
05 Apr 2013 |
Protocol Version 24, 15.01.2013: new study site |
||
12 Sep 2013 |
Protocol Version 26, 21.08.2013: recommendation on prior therapy new SmPC |
||
04 Aug 2014 |
Protocol Version 27, 02.06.2014: new SmPC |
||
01 Aug 2016 |
Protocol Version 29, 06.07.2016: new PPP (Pregnancy Prevention Plan) |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/32817078 |
|||
