Clinical Trial Results:
Safety and efficacy of interleukin-1 inhibitor anakinra for the amelioration of fever during neutropenia and mucositis in patients with multiple myeloma receiving an autologous hematopoietic stem cell transplantation after high-dose melphalan.
Summary
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EudraCT number |
2016-004419-11 |
Trial protocol |
NL |
Global end of trial date |
03 Apr 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Aug 2021
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First version publication date |
29 Aug 2021
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Other versions |
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 |
SC35
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03233776 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboud university medical center
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Sponsor organisation address |
Geert Grooteplein Zuid 8, Nijmegen, Netherlands, 6525 GA
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Public contact |
Trialbureau Hematologie-Oncologie, Radboud university medical center, +31 243614794, trialbureauhemat-onco@radboudumc.nl
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Scientific contact |
Trialbureau Hematologie-Oncologie, Radboud university medical center, +31 243614794, trialbureauhemat-onco@radboudumc.nl
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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 |
01 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Apr 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 |
The primary objective is to evaluate the safety and efficacy of anakinra in patients with multiple myeloma receiving high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (SCT).
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Protection of trial subjects |
Adverse events were monitored and recorded. The study was monitored by an independent monitor.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Mar 2017
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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 |
Netherlands: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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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) |
4
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
Pre-assignment
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Screening details |
105 patients were considered for inclusion. 79 were not selected because of comorbidities, inclusion in other trials, not interested, treatment in other hospitals, completion of study etc. 26 patients were selected for screening of whom 9 were included. The other 17 patients were not interested, did not fulfill the criteria or were not needed. | ||||||
Pre-assignment period milestones
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Number of subjects started |
9 | ||||||
Number of subjects completed |
9 | ||||||
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 |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
The results of the investigational blood cultures are blinded.
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Arms
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Arm title
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All subjects | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Anakinra
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Investigational medicinal product code |
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Other name |
Kineret
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects will be treated with anakinra in an increasing dose, according to 3+3 design. Predefined doses of anakinra are 100 mg, 200 mg and 300 mg. Subjects will receive anakinra once daily, starting on day -2, until day +12. Subjects will receive an intravenous dose of anakinra, given in a volume of 50 mL, administered with an infusion speed of 30 ml/hour, through a central venous catheter.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
100mg
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
First group of subjects treated with 100mg Anakinra.
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Subject analysis set title |
200mg
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Second group of subjects treated with 200mg Anakinra.
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Subject analysis set title |
300mg
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Third group of subjects treated with 300mg Anakinra.
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End points reporting groups
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Reporting group title |
All subjects
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Reporting group description |
- | ||
Subject analysis set title |
100mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
First group of subjects treated with 100mg Anakinra.
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Subject analysis set title |
200mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Second group of subjects treated with 200mg Anakinra.
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Subject analysis set title |
300mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Third group of subjects treated with 300mg Anakinra.
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End point title |
Safety [1] | |||||||||||||||
End point description |
All subjects who have received study medication in this study will be part of the safety and tolerability evaluation. Adverse events will be monitored throughout the study.
Safety measurements: Non-hematological grade 3-4 side effects will be graded according to the common toxicity criteria (CTCAE) and will be reported as DLT. Hematologically, period to neutrophil recovery will be recorded. Finally, serious infections and opportunistic infections will be recorded.
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End point type |
Primary
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End point timeframe |
Adverse events will be recorded from day of admission (day -3) until 30 days following the last dose of the investigational treatment. Adverse events occurring after 30 days should also be recorded if considered at least possibly related to the treatment
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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: Statistical analysis is not applicable for this endpoint. For safety, DLTs, SAEs and SUSARs were scored. These did not occur in any dose group. |
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No statistical analyses for this end point |
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End point title |
Maximum tolerated dose [2] | ||||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Not applicable
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Notes [2] - 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: Statistical analysis is not applicable for this endpoint. The maximum tolerated dose was concluded to be 300 mg, since no DLTs occurred in any dose group, and 300 mg was the maximum dose tested. |
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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 will be recorded from day of admission (day -3) until 30 days following the last dose of the investigational treatment. Adverse events occurring after 30 days should also be recorded if considered at least possibly related to the treatment
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
All subjects
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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 |