Condition category
Cancer
Date applied
27/06/2007
Date assigned
27/06/2007
Last edited
05/07/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.umcutrecht.nl/zorg/

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

  1. 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.

Additional files

Editorial Notes