Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells
N/A
N/A
Both
Bone Metastases of a Malignant Tumor
Trial Information
Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells
A total of 40 patients will be entered in this study. Half of the patients will receive
standard intravenous treatment with aminobsiphosphonates, the other half will be
additionally be treated with a statin. Patients already receiving statin treatment will
continue this treatment, other patients will be asked whether they are willing to be treated
with a statin for a maximum of 5 weeks. Consenting patients will be randomized to receive
i.v. aminobisphosponates plus or minus simvastatin 40 mg once daily. Simvastatin will be
started one week prior to the first administration of aminobisphosphonates and continued for
a maximum of 5 weeks. In each patient 10 ml peripheral blood will be drawn (t=0, t=24 hr,
t=1 week, t=3-4 weeks (prior to the 2nd aminobisphosphonate administration). In addition,
patients will be requested to measure their temperature thrice daily during the 2 days
following the first aminobisphosponate administration. This, because a relation between the
occurrence of a febrile response upon aminobisphosponate administration and an activation
and expansion of Vy9Vd2-T cells has been suggested. Peripheral blood mononuclear cells will
be isolated from the drawn peripheral blood. Using intra- and extracellular flowcytometry
Vy9Vd2-T cells will be characterized phenotypically (APC markers: CD1d, CD40, CD80, CD83,
CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7) and functionally
(IFN-γ, TNF-α, granzyme B). In addition, the frequency of CD3+, CD4+, CD8+ T cells, NK
cells, B cells, iNKT cells, CD4+CD25+ regulatory T cells, and circulating dendritic cells
will be assessed.
Inclusion Criteria:
- Patients with an indication for intravenous treatment with an aminobiphosphonate
because of a malignant tumor
- WHO 0,1,2 performance score
Exclusion Criteria:
- WHO 3, 4 performance score
- prior or current use of aminobisphosphonates -immunosuppressive medication (NSAID
allowed)
- chemotherapy and/or radiotherapy in 4 weeks prior to start of aminobisphosphonate
administration
- renal insufficiency (creatinine clearance < 30 ml/min)
- liver enzyme abnormalities:
- bilirubin > 1.5 times ULN (upper limit of normal)
- ASAT or ALAT > 2.5 times ULN (in absence of liver metastases)
- ASAT or ALAT > 5 times ULN (in presence of liver metastases)
- concomitant use of strong inhibitors of CYP3A4, such as itraconazole, ketoconazole,
erytromycin, clarithromycin, hiv-protease inhibitors or grapefruit juice is
contra-indicated.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Phenotypic (APC markers: CD1d, CD40, CD80, CD83, CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7)changes in the circulating pool of Vy9Vd2-T cells.
Outcome Description:
Peripheral blood mononuclear cells will be isolated from the drawn peripheral blood. Using intra- and extracellular flowcytometry Vy9Vd2-T cells will be characterized phenotypically (APC markers: CD1d, CD40, CD80, CD83, CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7).
Outcome Time Frame:
5 weeks
Safety Issue:
No
Principal Investigator
J J van der Vliet, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
VU University Medical Center
Authority:
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study ID:
2010/70
NCT ID:
NCT01179464
Start Date:
August 2010
Completion Date:
May 2013
Related Keywords:
- Bone Metastases of a Malignant Tumor
- Neoplasms
- Neoplasm Metastasis
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