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
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	04/239, NL962 (NTR988)
Sponsor	University Medical Centre Utrecht (UMCU) (The Netherlands)
Funders	Dutch Cancer Society (The Netherlands), International Myeloma Foundation (USA)

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

Primary study design	Interventional
Study design	Prospective phase II feasibility study
Secondary study design	Single-centre
Scientific title	High dose simvastatin combined with standard chemotherapy in patients with refractory Multiple Myeloma: a phase II study
Study objectives	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(s)	Received from the METC Medisch Ethische Toetsingscommissie on the 3rd May 2005 (ref: 04/239-E).
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Simvastatin, chemotherapy (vincristin, adriamycin, dexamethasone)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	14/09/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Not Specified
Target sample size at registration	12
Total final enrolment	12
Key inclusion criteria	1. Multiple myeloma patients 2. At least two cycles of chemotherapy with adriamycin and dexamethasone 3. Aged less than 75 years
Key exclusion criteria	1. Inadequate hepatic and renal function
Date of first enrolment	03/05/2005
Date of final enrolment	14/09/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Centre Utrecht

Utrecht
3508 AB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

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