Contact information
Type
Scientific
Primary contact
Dr E. van der Spek
ORCID ID
Contact details
University Medical Centre Utrecht
Department of Hematology
P.O. Box 85500
Utrecht
3508 AB
Netherlands
+31 (0)30 250 7655
e.vanderspek@umcutrecht.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
04/239
Study information
Scientific title
Acronym
Study hypothesis
Simvastatin (an Hydroxymethylglutaryl-coenzyme A [HMG-CoA] reductase inhibitor) induces apoptosis in vitro and sensitises the myeloma cell to chemotherapy. This is the first clinical trial to test if in vivo there is the same sensitisation in relapse or refractory multiple myeloma.
Ethics approval
Received from the METC Medisch Ethische Toetsingscommissie on the 3rd May 2005 (ref: 04/239-E).
Study design
Prospective phase II feasibility study
Primary study design
Interventional
Secondary study design
Single-centre
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Multiple myeloma
Intervention
Treatment of relapsed/refractory multiple myeloma patients with high dose statins, combined with chemotherapy. We treat multiple myeloma patients with 15 mg/kg simvastatin Day 0 - 7 followed by VAD day 7 - 11 (vincristin, adriamycin, dexamethasone) chemotherapy in a scheme as used in HOVON trials (e.g., HOVON 65; ISRCTN64455289). On day 29 a new cycle is started. Patients are treated with three cycles. An additional cycle can be given in case of response (MR, PR ,CR).
In case of progressive disease during treatment, the therapy is ended.
Intervention type
Drug
Phase
Phase II
Drug names
Simvastatin, chemotherapy (vincristin, adriamycin, dexamethasone)
Primary outcome measures
The primary endpoint is response as defined by the European Group for Blood and Marrow Transplantation (EBMT) criteria. This group of extensively pre-treated patients are multi-resistant and we defined - based in literature - a response of 10 - 30% as reasonable.
The primary endpoint (response) is measured during and after the trial by measurement of the M-protein measured in serum (an excellent tumour marker in multiple myeloma). After every cycle of 29 days M-protein will be measured. The M-protein will then be measured monthly until disease progression.
Secondary outcome measures
We recently performed a phase I study to define the Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) (published in Haematologica 2006; 91:542-545) of high dose simvastatin, combined with VAD. The secondary outcome of this trial is to confirm the feasibility as shown in the previous phase I trial.
Overall trial start date
03/05/2005
Overall trial end date
14/09/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Multiple myeloma patients
2. At least two cycles of chemotherapy with adriamycin and dexamethasone
3. Aged less than 75 years
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
12
Participant exclusion criteria
1. Inadequate hepatic and renal function
Recruitment start date
03/05/2005
Recruitment end date
14/09/2006
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Centre Utrecht
Utrecht
3508 AB
Netherlands
Sponsor information
Organisation
University Medical Centre Utrecht (UMCU) (The Netherlands)
Sponsor details
Department of Haematology
P.O. Box 85500
Utrecht
3508 GA
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
Dutch Cancer Society (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
International Myeloma Foundation (USA)
Alternative name(s)
IMF
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
Protocol in http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17107282
Publication citations
-
Protocol
Bringhen S, Avonto I, Magarotto V, Boccadoro M, Palumbo A, Investigational treatments for multiple myeloma., Expert Opin Investig Drugs, 2006, 15, 12, 1565-1582, doi: 10.1517/13543784.15.12.1565.