High dose simvastatin combined with standard chemotherapy in patients with refractory Multiple Myeloma: a phase II study

ISRCTN ISRCTN85384018
DOI https://doi.org/10.1186/ISRCTN85384018
Secondary identifying numbers 04/239, NL962 (NTR988)
Submission date
27/06/2007
Registration date
27/06/2007
Last edited
27/10/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr E. van der Spek
Scientific

University Medical Centre Utrecht
Department of Hematology
P.O. Box 85500
Utrecht
3508 AB
Netherlands

Phone +31 (0)30 250 7655
Email e.vanderspek@umcutrecht.nl

Study information

Study designProspective phase II feasibility study
Primary study designInterventional
Secondary study designSingle-centre
Study setting(s)Hospital
Study typeTreatment
Scientific titleHigh dose simvastatin combined with standard chemotherapy in patients with refractory Multiple Myeloma: a phase II study
Study objectivesSimvastatin (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(s)Received from the METC Medisch Ethische Toetsingscommissie on the 3rd May 2005 (ref: 04/239-E).
Health condition(s) or problem(s) studiedMultiple myeloma
InterventionTreatment 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Simvastatin, chemotherapy (vincristin, adriamycin, dexamethasone)
Primary outcome measureThe 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 measuresWe 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 study start date03/05/2005
Completion date14/09/2006

Eligibility

Participant type(s)Patient
Age groupAdult
SexNot Specified
Target number of participants12
Total final enrolment12
Key inclusion criteria1. Multiple myeloma patients
2. At least two cycles of chemotherapy with adriamycin and dexamethasone
3. Aged less than 75 years
Key exclusion criteria1. Inadequate hepatic and renal function
Date of first enrolment03/05/2005
Date of final enrolment14/09/2006

Locations

Countries of recruitment

  • Netherlands

Study participating centre

University Medical Centre Utrecht
Utrecht
3508 AB
Netherlands

Sponsor information

University Medical Centre Utrecht (UMCU) (The Netherlands)
Hospital/treatment centre

Department of Haematology
P.O. Box 85500
Utrecht
3508 GA
Netherlands

Website http://www.umcutrecht.nl/zorg/
ROR logo "ROR" https://ror.org/04pp8hn57

Funders

Funder type

Research organisation

Dutch Cancer Society (The Netherlands)

No information available

International Myeloma Foundation (USA)
Government organisation / Trusts, charities, foundations (both public and private)
Alternative name(s)
Myeloma, Intl. Myeloma Foundation, IMF
Location
United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article Protocol 01/12/2006 Yes No
Results article 01/12/2007 27/10/2021 Yes No

Editorial Notes

27/10/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.