Clinical Trial Results:
The combination of Lenalidomide and Dexamethasone with or without intensification by high-dose Melphalan in the treatment of multiple myeloma
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Summary
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EudraCT number |
2008-004083-39 |
Trial protocol |
DE |
Global end of trial date |
31 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Jun 2022
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First version publication date |
09 Jun 2022
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Other versions |
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Summary report(s) |
Justification no results in EudraCT |
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 |
DSMM_XIII
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01090089 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GMIHO Gesellschaft für Medizinische Innovation – Hämatologie und Onkologie mbH
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Sponsor organisation address |
Almstadtstraße 7, Berlin, Germany, 10119
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Public contact |
GMIHO, GMIHO Gesellschaft für Medizinische Innovation – Hämatologie und Onkologie mbH, 0049 351 25 933100, info@gmiho.de
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Scientific contact |
GMIHO, GMIHO Gesellschaft für Medizinische Innovation – Hämatologie und Onkologie mbH, 0049 351 25 933100, info@gmiho.de
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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 |
24 May 2022
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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 |
31 Jan 2020
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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 compare the efficacy of both treatment regimens with regard to progression-free survival.
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Protection of trial subjects |
The conduct, documentation and evaluation of this study was compliant to Good Clinical Practice 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 adverse clinical experiences observed by the investigator and reported by the patient were recorded with details about duration and intensity of each episode as well as action taken related to the study drug and its outcome. The investigator had to evaluate each adverse experience for its relationship to the study drug and for its seriousness. Moreover, during and after each cycle the observed toxicity of treatment was considered for continuation of therapy and indicated dose modifications had to be performed. Furthermore, the investigator had to assess all abnormal laboratory results for their clinical significance. If any abnormal laboratory result considered clinically significant, the investigator had to provided details about the action taken in relation to the study drug and the outcome.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Mar 2010
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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 |
Germany: 348
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Worldwide total number of subjects |
348
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EEA total number of subjects |
348
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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) |
0
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From 65 to 84 years |
348
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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 |
Approximately 348 patient with multiple myeloma (MM) should screened for enrollment at 40 sites in Germany. | |||||||||
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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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Arm A1 | |||||||||
Arm description |
In patients in treatment arm A1 the therapy with lenalidomide and low-dose dexamethasone (Rd) were continued when stem cell mobilization and harvest of peripheral blood stem cells (PBSC) was finished, usually 3-4 weeks after the start of stem cell mobilization therapy. The study treatment with lenalidomide and low-dose dexamethasone was given until progression and stopped when progression was documented or when intolerable side effects occurred. Patients in arm A1 treated with autologous stem cell transplantation only in case of relapse or progression. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lenalidomide
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Investigational medicinal product code |
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Other name |
Revlimid®
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg orally once daily on days 1 to 21 of repeated 28 days cycles until progression or intolerable side effects
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Investigational medicinal product name |
Dexamethasone
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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 |
40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28 days cycles until progression or intolerable side effects
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Arm title
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Arm A2 | |||||||||
Arm description |
Patients in arm A2 received a tandem high-dose melphalan (140 mg/m²) with peripheral blood stem cell transplantation (PBSCT) after stem cell mobilization and PBSC. Accordingly, patients who had a sufficient stem cell transplant got the first melphalan (140 mg/m²) within 2-4 weeks after stem cell harvest. The second melphalan (140 mg/m²) was scheduled two months after the first melphalan (140 mg/m²). In treatment arm A2 lenalidomide (10 mg/day) maintenance was applied and started within 2-3 months from the second PBSCT for patients without signs of progression who had an adequate reconstitution of hematopoiesis post–transplant. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Lenalidomide
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Investigational medicinal product code |
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Other name |
Revlimid®
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Mode of administration:
induction therapy: 25 mg orally once daily on days 1 to 21 of repeated 28 days cycles for 3 cycles
maintenance therapy: 10 mg orally once daily of repeated 28 days cycles until progression or intolerable side effects
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Investigational medicinal product name |
Dexamethasone
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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 |
induction therapy: 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28 days cycles for 3 cycles
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Investigational medicinal product name |
Melphalan
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
first high-dose 140 mg/m² intravenous infusion followed by PBSCT 2-4 weeks after stem cell harvest; second high-dose 140 mg/m² intravenous infusion followed by PBSCT after 2 months of first high-dose 140 mg/m² administration
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End points reporting groups
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Reporting group title |
Arm A1
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Reporting group description |
In patients in treatment arm A1 the therapy with lenalidomide and low-dose dexamethasone (Rd) were continued when stem cell mobilization and harvest of peripheral blood stem cells (PBSC) was finished, usually 3-4 weeks after the start of stem cell mobilization therapy. The study treatment with lenalidomide and low-dose dexamethasone was given until progression and stopped when progression was documented or when intolerable side effects occurred. Patients in arm A1 treated with autologous stem cell transplantation only in case of relapse or progression. | ||
Reporting group title |
Arm A2
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Reporting group description |
Patients in arm A2 received a tandem high-dose melphalan (140 mg/m²) with peripheral blood stem cell transplantation (PBSCT) after stem cell mobilization and PBSC. Accordingly, patients who had a sufficient stem cell transplant got the first melphalan (140 mg/m²) within 2-4 weeks after stem cell harvest. The second melphalan (140 mg/m²) was scheduled two months after the first melphalan (140 mg/m²). In treatment arm A2 lenalidomide (10 mg/day) maintenance was applied and started within 2-3 months from the second PBSCT for patients without signs of progression who had an adequate reconstitution of hematopoiesis post–transplant. | ||
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End point title |
progression-free survival (PFS) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
from the time point of randomization until progression or intolerable side effects
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Statistical analysis title |
No analysis | ||||||||||||
Comparison groups |
Arm A1 v Arm A2
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Number of subjects included in analysis |
348
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.045 | ||||||||||||
Method |
t-test, 1-sided | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
until progression
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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 |
24.0
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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: Due to the COVID-19 pandemic and its lockdown and restrictions the planned monitoring activities could not be entirely performed. Therefore, no or limited source data verification (SDV) for endpoints at the sites were possible. Obligatory established hygienical concepts also resulted to significant delays in collecting remaining data. This led to the fact that the data for the final analysis were not available at the scheduled time. |
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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 | |||
