Clinical Trial Results:
Bendamustine, Prednisone and Velcade® for first-line treatment of patients with symptomatic multiple myeloma not eligible for high-dose chemotherapy followed by autologous stem cell transplantation (BPV).
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Summary
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EudraCT number |
2013-005485-19 |
Trial protocol |
DE |
Global end of trial date |
23 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Apr 2022
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First version publication date |
28 Apr 2022
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Other versions |
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Summary report(s) |
BPVSummary |
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 |
BPV
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02237261 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Heidelberg University Hospital
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Sponsor organisation address |
Im Neuenheimer Feld 672, Heidelberg, Germany, 69120
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Public contact |
GMMG Studiensekretariat
Medizinische Klinik V und Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg
INF130.3
69120 Heidelberg
Germany, +49 6221 568198, S.GMMG@med.uni-heidelberg.de
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Scientific contact |
GMMG Studiensekretariat
Medizinische Klinik V und Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg
INF 130.3
69120 Heidelberg
Germany, +49 6221 568198, S.GMMG@med.uni-heidelberg.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 |
11 Jun 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Aug 2018
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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 main purpose of the study is to demonstrate the efficacy of BPV to efficiently decrease myeloma tumor burden.
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Protection of trial subjects |
Safety date were reviewed by a DSMB
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Nov 2014
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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 |
Germany: 46
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Worldwide total number of subjects |
46
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EEA total number of subjects |
46
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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) |
2
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From 65 to 84 years |
44
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85 years and over |
0
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Recruitment
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Recruitment details |
For recruitment patients diagnosed with multiple myeloma requiring systemic treatment (in accordance to CRAB criteria) were informed regarding the trial and offered to undergo screening examination for inclusion. Written informed consent was mandatory for inclusion into the trial. | ||||||
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Pre-assignment
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Screening details |
Prior to inclusion, patients had to be registered at the GMMG by fax, including information regarding eligibility criteria and the investigational site. Also, data of the following parameters were transmitted: Serum M-protein (concentration of monoclonal protein in serum) Urine M-protein (Bence Jones) sFLC in case of hyposecretory myeloma. | ||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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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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Treatment arm | ||||||
Arm description |
First line treatment of patients with symptomatic multiple myeloma | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
bendamustine
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Investigational medicinal product code |
LO1AA09
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Other name |
Levact(R)
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
All patients received bendamustine in a dose of 90 mg/m2 body surface area (BSA).
Bendamustine was administered by i.v. infusion over 30-60 minutes.
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Investigational medicinal product name |
prednisone
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Investigational medicinal product code |
H02AB07
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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 |
60mg/m² as Tablets days 1-4
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Investigational medicinal product name |
bortezomib
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Investigational medicinal product code |
ATC code LO1AA09
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Other name |
Velcade ®
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Pharmaceutical forms |
Powder for concentrate for solution for injection/infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
All patients received bortezomib in a dose of 1.3 mg/m2 body surface area (BSA) as a subcutaneous injection.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Treatment group only (no comparator) | |||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Per Protocol
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Of all patients included, 33 fulfilled the criteria of the per-protocol analysis set, in particular the completion of 3 cycles of treatment.
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Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
In this data set, all 46 patients included were analysed.
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End points reporting groups
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Reporting group title |
Treatment arm
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Reporting group description |
First line treatment of patients with symptomatic multiple myeloma | ||
Subject analysis set title |
Per Protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Of all patients included, 33 fulfilled the criteria of the per-protocol analysis set, in particular the completion of 3 cycles of treatment.
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Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
In this data set, all 46 patients included were analysed.
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End point title |
Overall response rate PP [1] | ||||||||||||||
End point description |
The overall response rate (ORR) was defined as PR or better during the 9 treatment cycles. Response to treatment was evaluated according to IMWG criteria. The PP population was defined as those patients in the ITT population who completed at least 3 cycles of BPV therapy and were evaluable for response without major protocol violations. Best response was used to calculate ORR.
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End point type |
Primary
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End point timeframe |
during 9 treatment cycles
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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: There was only one treatment arm in this study (no control group). The following estimate was calculated in comparison to a predefined ORR of 67%. The 95% one-sided confidence interval was identified as mean 0.7879, lower 0.6495, and p-value 0.0876. Despite the positive therapeutic results for the PP population, the statistical analysis could not confirm a statistically significant increase in ORR above 67% as predefined to reject the H0 hypothesis. |
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Attachments |
Untitled (Filename: BPV_analysisPP.png) |
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End point title |
renal outcome | |||||||||||||||
End point description |
to investigate the percentage of patients with recovery/improvement of renal function (for patients with impaired renal function at baseline, n= 19)
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End point type |
Secondary
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End point timeframe |
during treatment cycles
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| Notes [2] - patients with impaired renal function at baseline [3] - Only patients with renal impairment at baseline were analysed |
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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 |
Adverse events that have a start date during or within 30 days after end of treatment.
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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 |
20.1/21.0
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
Fatal adverse events. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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13 Apr 2016 |
Reduction of sample size |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/32155662 |
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