Essential thrombocythemia, Polycythemia vera, prefibrotic myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10077465 Term: Myeloproliferative neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Atorvastatin
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Atorvastatin
CAS Number: 134523-00-5
Concentration unit: mg milligram(s)
Concentration type: range
Concentration numb
Sponsors
Zealand University Hospital, dept. of Haematology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: WHO 2016 classified ET, PV or prePMF with thrombocytosis and/or leukocytosis. 2. Age > 18 years. 3. Expected survival > 3 years. 4. If ongoing cytoreductive treatment, this must have started > 3 months ago, and there must not be an expected change of dose or treatment type in the coming year. 5. Not taking statin beforehand Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Uncontrolled autoimmune or chronic inflammatory disorder (covers unexplained inflammatory condition, inadequately treated inflammatory condition, and treatment with strong immunosuppressive medications). 2. Other active cancer (excluding squamous cell carcinoma or basal cell carcinoma in the skin and prostate cancer treated with "watchful waiting"). 3. Pregnancy 4. Contraindications against starting atorvastatin: a. Active liver disease or persistent transaminase elevation of unknown cause. b. Concomitant use of potent CYP3A4 inhibitors c. Combination with gemfibrozil or ciclosporin d. Allergy to statins
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. In patients with MPNs undergoing Best Available Therapy (BAT), to investigate the effect of adjuvant treatment with atorvastatin assessed by inflammatory markers and cell counts.;Primary end point(s): Primary: 1. Inflammatory parameters: hs-CRP, inflammatory cytokines, leukocyte count, platelet count and neutrophil/lymphocyte ratio (NLR). ;Secondary Objective: 2. To asses biochemical markers for inflammation and disease burden in a population of MPN patients who are followed prospectively during statin treatment, as well as to assess the relationship to the development of symptoms, thrombosis and transformation to myelofibrosis and AML. 3. To asses the thrombophilia profile in MPN patients before and during atorvastatin treatment. 4. To asses the number and functionality of circulating immune cells before and during atorvastatin treatment. 5. To investigate the effect of statins on the gut microbiome and possible correlations in treatment response. ;Timepoint(s) of evaluation of this end point: baseline, 1, 3, 6, 7, 9, 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary: 2. Hematological parameters: hemoglobin, hematocrit, erythrocyte count, LDH and urate. 3. Inflammatory parameters and coagulation factors: Ferritin, fibrin D-dimer, SR, fibrinogen. 4. MPN-related symptoms. 5. Number of phlebotomies and blood transfusions. 6. Types and dose of cytoreductive treatment. 7. Molecular biological parameters: JAK2-V617F allele burden (qPCR) and CALR mutation allele burden. JAK2-V617F positive patients only have JAK2-V617F allele burden taken and CALR mutation positive patients only have CALR allele burden taken. 8. Cholesterols: HDL, LDL, VLDL, total cholesterol + triglycerides - Measures of effect of statins and related to correlate statins effect on lipid profile and inflammatory biomarkers. Also measures of compliance to atorvastatin treatment. 9. Markers of oxidative stress in urine: 8-oxoGuo and 8-oxodG. 10. Next generation exome sequencing 11. Immune cell studies and NETosis activity. 12. ROTEM study for thrombophilia/coagulation status. 13. Assessment of endothelial dysfunction on the basis of EndoPAT measurements. 14. Eye examination. 15. Registration of side effects for atorvastatin. 16. Quality of life form MPN-SAF, which was part of the department's ongoing assessment of quality of life for hematology patients 17. Plasma proteomics and plasma metabolomics 18. Microbiome studies ;Timepoint(s) of evaluation of this end point: baseline, 1, 3, 6, 7, 9, 12 months (not every secondary endpoint will be assesed at each timepoint) | — |
Countries
Denmark
Contacts
Public Contact.
Zealand University Hospital, dept. of Haematology
Outcome results
None listed