Clinical Trial Results:
Phase II study of carfilzomib- cyclophosphamide-dexamethasone and high-dose melphalan followed by randomization between observa-tion or maintenance with carfil-zomib and dexamethasone in pa-tients with relapsed multiple myeloma after high-dose melphalan with autologous stem cell support
Summary
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EudraCT number |
2013-003789-15 |
Trial protocol |
DK FI SE NO LT |
Global end of trial date |
01 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
10 May 2021
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First version publication date |
10 May 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 |
NMSG#20/13
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02572492 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Nordic Myeloma Study Group
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Sponsor organisation address |
Mølleparkvej 4, Aalborg, Denmark, 9000
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Public contact |
Clinical Trial Unit Hematology
Aalborg University Hospital
Mølleparkvej 4
9000 Aalborg
Denmark, Nordic Myeloma Study Group, 0045 97663884, henrik.gregersen@rn.dk
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Scientific contact |
Clinical Trial Unit Hematology
Aalborg University Hospital
Mølleparkvej 4
9000 Aalborg
Denmark, Nordic Myeloma Study Group, 0045 97663884, henrik.gregersen@rn.dk
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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 |
06 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Sep 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Sep 2019
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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 purpose of our study is to evaluate the effect of the combination of carfilzomib, cyclophosphamide and dexamethasone in the induction regimen and carfilzomib in the conditioning regimen of salvage HDT. In addition to evaluate the potential effect of carfilzomib/dexamethasone maintenance treatment.
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Protection of trial subjects |
Exclusion criteria regarding heart disease e.g. exclusion of patients with uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, NYHA Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, uncontrolled severe arrhytmias, or cardiac amyloidosis. In addition LVEF <40%, determined by 2-D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA)
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jan 2014
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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: 58
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Country: Number of subjects enrolled |
Sweden: 50
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Country: Number of subjects enrolled |
Denmark: 66
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Country: Number of subjects enrolled |
Finland: 10
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Country: Number of subjects enrolled |
Lithuania: 16
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Worldwide total number of subjects |
200
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EEA total number of subjects |
200
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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) |
138
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From 65 to 84 years |
62
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from NMSG centers in Denmark, Sweden, Norway, Finland and Lithuania | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Multiple myeloma patients with first relapse more than one year after single or double high-dose melphalan with stem cell support | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Induction and salvage ASCT (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Arm title
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CA-CY-DEX and salvage ASCT | ||||||||||||||||||||||||
Arm description |
Included patients received: Four cycles of CAR-CY-DEX (iv carfilzomib, p.o. cyclophosphamide and p.o. dexamethasone Conditioning regimen: Iv carfilzomib on day –2 and –1 and iv melphalan 200 mg/sqm on day –2. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Carfilzomib
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Investigational medicinal product code |
L01XG02
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Induction regime:
Four cycles of CAR-CY-DEX (Cycle 1 with iv carfilzomib 20 mg/sqm on days 1 and 2, and iv carfilzomib 36 mg/sqm on days 8, 9, 15 and 16. Cycle 2 - 4 with iv carfilzomib 36 mg/sqm on days 1, 2, 8, 9, 15 and 16. P.o. cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and p.o. dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days cycle).
Conditioning regimen:
Iv carfilzomib 27 mg/sqm on day –2 and –1
Iv melphalan 200 mg/sqm on day –2
> 2.0 x 106 CD34+ stem cells/kg body weight on day 0
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Baseline characteristics reporting groups
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Reporting group title |
Induction and salvage ASCT
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
CAR-CY-DEX and salvage ASCT
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||
Subject analysis set description |
CAR-CY-DEX and salvage ASCT
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End points reporting groups
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Reporting group title |
CA-CY-DEX and salvage ASCT
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Reporting group description |
Included patients received: Four cycles of CAR-CY-DEX (iv carfilzomib, p.o. cyclophosphamide and p.o. dexamethasone Conditioning regimen: Iv carfilzomib on day –2 and –1 and iv melphalan 200 mg/sqm on day –2. | ||
Subject analysis set title |
CAR-CY-DEX and salvage ASCT
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
CAR-CY-DEX and salvage ASCT
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End point title |
Comparison of time to progression (TTP) after first high-dose melphalan with stem cell support (HDT) and TTP after a second HDT combined with carfilzomib-cyclophosphamide-dexamethasone (CAR-CY-DEX) | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From inclusion until end of study
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Statistical analysis title |
Comparison of TTP | ||||||||||||||||||
Statistical analysis description |
Mann-Whitney test
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Comparison groups |
CA-CY-DEX and salvage ASCT v CAR-CY-DEX and salvage ASCT
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Number of subjects included in analysis |
336
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||
Confidence interval |
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End point title |
Treatment response after four cycles of CAR-CY-DEX induction | ||||||||
End point description |
No difference compared with VGPR, CR or sCR after induction therapy after up-front ASCT
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End point type |
Secondary
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End point timeframe |
VGPR, CR or sCR after CAR-CY-DEX induction before salvage ASCT
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No statistical analyses for this end point |
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End point title |
Time to marrow regeneration (neutrophil- and platelet recovery) after the salvage ASCT | ||||||||||||
End point description |
Mean time to neutrophils above 1.0 × bn/L after salvage ASCT and mean time to thrombocytes above 100 × 10 bn/L after salvage ASCT.
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End point type |
Secondary
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End point timeframe |
Time to marrow regeneration (neutrophil- and platelet recovery) after the HDT
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No statistical analyses for this end point |
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End point title |
Response rates of induction therapy and HDT | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Treatment response after CAR-CY-DEX induction and salvage ASCT
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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 |
From inclusion until 60 days after salvage ASCT
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
NCI CTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
CAR-CY-DEX and salvage ASCT
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Reporting group description |
Included patients received: Four cycles of CAR-CY-DEX (iv carfilzomib, p.o. cyclophosphamide and p.o. dexamethasone Conditioning regimen: Iv carfilzomib on day –2 and –1 and iv melphalan 200 mg/sqm on day –2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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. | |||
No |