Clinical Trial Results:
A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma

Trial information Top of page
Trial identification
Sponsor protocol code	DMSG03/14
Additional study identifiers
ISRCTN number	-
US NCT number	NCT02573935
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Aalborg University Hospital
Sponsor organisation address	Møllleparkvej 4, Aalborg, Denmark, 9000
Public contact	Clinical Trial Unit Hematology, Danish Myeloma Study Group, +45 97663880, henrik.gregersen@rn.dk
Scientific contact	Clinical Trial Unit Hematology, Danish Myeloma Study Group, +45 97663880, henrik.gregersen@rn.dk
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	01 Jun 2018
Is this the analysis of the primary completion data?	Yes
Primary completion date	01 Jun 2018
Global end of trial reached?	Yes
Global end of trial date	01 Jun 2018
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	The purpose of our study was to evaluate the effect of clarithromycin in combination with VCD induction therapy in patients with newly diagnosed multiple myeloma
Protection of trial subjects	Robust rules for concomitant medication. Frequent ECG during early phase of trial.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	01 Oct 2014
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Denmark: 58
Worldwide total number of subjects	58
EEA total number of subjects	58
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)	39
From 65 to 84 years	19
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Myeloma patients eligible for high-dose melphalan with stem cell support
Pre-assignment
Screening details	Myeloma patients eligible for high-dose melphalan with stem cell support
Pre-assignment period milestones
Number of subjects started	58
Number of subjects completed
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor
Arms
Are arms mutually exclusive	Yes
Arm title	Clarithromycin
Arm description	Combination of clarithromycin and VCD
Arm type	Experimental
Investigational medicinal product name	Clarithromycin
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	500 mg twice daily for 63 days
Arm title	Placebo
Arm description	Combination of placebo and VCD
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	1 Tablet twice daily for 63 days
Number of subjects in period 1 Clarithromycin Placebo Started 27 31 Completed 22 28 Not completed 5 3      Adverse event, non-fatal 5 3

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial
Reporting group description	-
Reporting group values Overall trial Total Number of subjects 58 58 Age categorical Units: Subjects     In utero 0     Preterm newborn infants (gestational age < 37 wks) 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) 0     From 65-84 years 0     85 years and over 0 Age continuous Units: years     median (inter-quartile range (Q1-Q3)) 63 (55 to 66) - Gender categorical Units: Subjects     Female 18 18     Male 40 40
Subject analysis sets
Subject analysis set title	Clarithromycin effect
Subject analysis set type	Full analysis
Subject analysis set description	Analysis of effect of clarithromycin added to VCD
Subject analysis sets values Clarithromycin effect Number of subjects 58 Age categorical Units: Subjects     In utero     Preterm newborn infants (gestational age < 37 wks)     Newborns (0-27 days)     Infants and toddlers (28 days-23 months)     Children (2-11 years)     Adolescents (12-17 years)     Adults (18-64 years)     From 65-84 years     85 years and over Age continuous Units: years     median (inter-quartile range (Q1-Q3)) 63 (55 to 66) Gender categorical Units: Subjects     Female 18     Male 40

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Clarithromycin
Reporting group description	Combination of clarithromycin and VCD
Reporting group title	Placebo
Reporting group description	Combination of placebo and VCD
Subject analysis set title	Clarithromycin effect
Subject analysis set type	Full analysis
Subject analysis set description	Analysis of effect of clarithromycin added to VCD

End points Top of page

Primary: VGPR or better response after VCD induction Top of page
End point title	VGPR or better response after VCD induction
End point description
End point type	Primary
End point timeframe	VGPR or better response after VCD induction
End point values Clarithromycin Placebo Number of subjects analysed 27 31 Units: VGPR or better response after VCD induct 12 16
Statistical analysis title	Fisher’s exact test
Comparison groups	Clarithromycin v Placebo
Number of subjects included in analysis	58
Analysis specification	Pre-specified
Analysis type	equivalence
P-value	< 0.05
Method	Fisher exact
Confidence interval

Primary: VGPR or better response after VCD induction Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From inclusion until completion of 4.VCD, equalling 84 days
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	NCI CTC
Dictionary version	4
Reporting groups
Reporting group title	Clarithromycin
Reporting group description	Combination of clarithromycin and VCD
Reporting group title	Placebo
Reporting group description	Combination of placebo and VCD
Serious adverse events Clarithromycin Placebo Total subjects affected by serious adverse events      subjects affected / exposed 16 / 27 (59.26%) 16 / 31 (51.61%)      number of deaths (all causes) 1 1      number of deaths resulting from adverse events 1 1 Gastrointestinal disorders Abdominal pain, neutropenic enterocolitis, paralytic ileus or peptic ulcer      subjects affected / exposed 9 / 27 (33.33%) 2 / 31 (6.45%)      occurrences causally related to treatment / all 9 / 9 2 / 2      deaths causally related to treatment / all 1 / 1 1 / 1 Infections and infestations Septicemia      subjects affected / exposed 5 / 27 (18.52%) 1 / 31 (3.23%)      occurrences causally related to treatment / all 5 / 5 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 2 / 27 (7.41%) 5 / 31 (16.13%)      occurrences causally related to treatment / all 0 / 2 0 / 5      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Clarithromycin Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 26 / 27 (96.30%) 28 / 31 (90.32%) Cardiac disorders Hypotension      subjects affected / exposed 6 / 27 (22.22%) 1 / 31 (3.23%)      occurrences all number 6 1 Nervous system disorders Peripheral sensory neuropathy      subjects affected / exposed 15 / 27 (55.56%) 8 / 31 (25.81%)      occurrences all number 15 8 Blood and lymphatic system disorders Thrombocytopenia      subjects affected / exposed 13 / 27 (48.15%) 7 / 31 (22.58%)      occurrences all number 13 7 Anemia      subjects affected / exposed 14 / 27 (51.85%) 11 / 31 (35.48%)      occurrences all number 14 11 Neutropenia      subjects affected / exposed 12 / 27 (44.44%) 13 / 31 (41.94%)      occurrences all number 12 13 Renal and urinary disorders Peripheral edema      subjects affected / exposed 12 / 27 (44.44%) 8 / 31 (25.81%)      occurrences all number 12 8 Psychiatric disorders Psychiatric symptoms      subjects affected / exposed 6 / 27 (22.22%) 3 / 31 (9.68%)      occurrences all number 6 3 Infections and infestations Infection      subjects affected / exposed 23 / 27 (85.19%) 24 / 31 (77.42%)      occurrences all number 23 24

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? Yes
Date Interruption Restart date 16 Sep 2016 The study was prematurely stopped for safety reasons after the inclusion of 58 patients (36% of the planned study population). -
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
The study included only 58 of planned patients
Online references
http://www.ncbi.nlm.nih.gov/pubmed/30123673 http://www.ncbi.nlm.nih.gov/pubmed/30230047

More information Top of page