Statin- and bisphosphonate treatment in patients with the Philadelphia-negative chronic myeloproliferative neoplasms - essential thrombocytosis, polycythemia vera and hypercellular myelofibrosis.

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-001406-42-DK

Enrollment

100

Registered

2016-04-07

Start date

2016-12-20

Completion date

Unknown

Last updated

2021-06-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

The Philadelphia-negative chronic myeloproliferative neoplasms: Essential thrombocytosis, polycythemia vera and hypercellular myelofibrosis. MedDRA version: 19.0 Level: LLT Classification code 10028577 Term: Myeloproliferative disorder NOS System Organ Class: 100000004864 MedDRA version: 19.0 Level: LLT Classification code 10074689 Term: Post polycythemia vera myelofibrosis System Organ Class: 100000004864 MedDRA version: 19.0 Level: LLT Classification code 10028576 Term: Myeloproliferative d

Interventions

Product Name: Atorvastatin Pharmaceutical Form: Tablet INN or Proposed INN: ATORVASTATIN CAS Number: 134523-00-5 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 20-

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Low-risk MPN patients 1. WHO 2016 classified ET, PV or hyperproliferativ primary myelofibrosis og prePMF (thrombocytosis and/or leukocytosis without anemia). 2. Age > 18 years. 3. Expected survival > 1 year. 4. Fulfills criteria for low-risk MPN disease: a. Age 18 years. 3. Expected survival > 1 year. 4. Fulfills criteria for high-risk MPN disease: a. Age > 60 years or b. Prior thrombosis or c. B-thrombocytes > 1500 x 109/l. 5. Does not use statin or bisphosphonate. Reactive thrombocytosis and/or leukocytosis 1. Referred on suspicion of MPNs. No suspicion of MPN disease. 2. Age > 18 years. 3. Expected survival > 1 year. 4. Does not use statin. 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

Exclusion criteria: General: 1. Uncontrolled autoimmune or chronic inflammatory disease 2. Different active cancer 3. Pregnancy (in fertile women pregnancy must be ruled out by negative pregnancy test and safe contraceptive treatment must be used). Low-risk MPN: 1. Contraindications against atorvastatin treatment a. Active lever disease or continuous elevated transaminases of unknown reasons b. Use of potent CYP3A4-inhibitors c. Use of gemfibrozil or ciclosporin d. Allergies against statins 2. Contraindications against zoledronic acid treatment a. Severe renal failure (GFR 6 b. Severe cardiac disease c. Autoimmune hepatitis d. Abnormal TSH (must be corrected) e. Allergies against interferon Reactive thrombocytosis and/or leukocytosis 1. Contraindications against atorvastatin treatment a. Active lever disease or continuous elevated transaminases of unknown reasons b. Use of potent CYP3A4-inhibitors c. Use of gemfibrozil or ciclosporin d. Allergies against statins

Design outcomes

Primary

Measure	Time frame
Main Objective: 1. In patients wit newly diagnosed low-risk MPNs to compare treatment with atorvastatin, zoledronic acid, atorvastatin + zoledronic acid and no treatment. 2. In patients wit newly diagnosed high-risk MPNs to compare treatment with interferon + atorvastatin, interferon + zoledronic acid, interferon + atorvastatin + zoledronic acid and interferon treatment alone.;Secondary Objective: 1. To describe biochemical markers of inflammation and disease burden in a population of MPN patients observed prospectively. 2. To describe the thrombophilic profile in MPN patients during treatment. 3. To describe Peripheral insulin resistence in patients with MPN at diagnosis at during treatment. 4. To describe circulating immune cell function at time of diagnosis and during treatment. 5. To describe MPN patients co-morbidity status at time of diagnosis. 6. To evaluate the effect of atorvastatin treatment in patients with reactive thrombocytosis and leucocytosis (non-MPN). 7. To describe biochemical markers of inflammation and disease burden in a population of non-MPN patients. 8. To describe if patients with non-MPN have peripheral insulin resistance, and to evaluate the effect of treatment. 9. To describe patients with non-MPN co-morbidity status at time of diagnosis. ;Primary end point(s): 1. Inflammatory biomarkers: hsCRP, inflammatory cytokines, leukocytecount, plateletcount.;Timepoint(s) of evaluation of this end point: baseline, 14 days, 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 months cytokine measurements baseline, 1, 3, 6 months.	—

Measure

Time frame

Main Objective: 1. In patients wit newly diagnosed low-risk MPNs to compare treatment with atorvastatin, zoledronic acid, atorvastatin + zoledronic acid and no treatment. 2. In patients wit newly diagnosed high-risk MPNs to compare treatment with interferon + atorvastatin, interferon + zoledronic acid, interferon + atorvastatin + zoledronic acid and interferon treatment alone.;Secondary Objective: 1. To describe biochemical markers of inflammation and disease burden in a population of MPN patients observed prospectively. 2. To describe the thrombophilic profile in MPN patients during treatment. 3. To describe Peripheral insulin resistence in patients with MPN at diagnosis at during treatment. 4. To describe circulating immune cell function at time of diagnosis and during treatment. 5. To describe MPN patients co-morbidity status at time of diagnosis. 6. To evaluate the effect of atorvastatin treatment in patients with reactive thrombocytosis and leucocytosis (non-MPN). 7. To describe biochemical markers of inflammation and disease burden in a population of non-MPN patients. 8. To describe if patients with non-MPN have peripheral insulin resistance, and to evaluate the effect of treatment. 9. To describe patients with non-MPN co-morbidity status at time of diagnosis. ;Primary end point(s): 1. Inflammatory biomarkers: hsCRP, inflammatory cytokines, leukocytecount, plateletcount.;Timepoint(s) of evaluation of this end point: baseline, 14 days, 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 months cytokine measurements baseline, 1, 3, 6 months.

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Secondary

Measure	Time frame
Secondary end point(s): 2. Hematological parameters: hgb, hct, erytrocytecount, MCV, differential count, reticulocytes, LDH and URAT 3. Inflammatory parameters and coagulationhemostasis: Ferritin, fibrin D-dimer, ESR, fibrinogen. 4. MPN related symptoms 5. Number of phlebotomies and transfusions. 6. The need for further cytoreductive treatment. 7. Response rates 8. Comparison of the bonemarrow after 3 years with pretreatment bone marrow. 9. CALR and JAK2 mutationburden 10. IgA, IgG, IgM 11. Cholesterol levels 12. YKL-40, myeloperoxidase, beta2-mikroglobulin. 13. markers of for oxidative stress in urine 8-oxoGua, 8-oxoGuo og 8-oxod-Guo. 14. Genexpressionsprofilering, next generation exomsekventering 15. Immunecell studies 16. ROTEM 17. Insulin resistance 18. EndoPat measurements 19. Echocardiografi, heart CT, cerebral blood flow, ultrasound of neck vessels and eye examination 20. Treatment sideeffects 21. Quality of life questionnaires MPN-SAF, BFI og EORTIC QLQ C-30 ;Timepoint(s) of evaluation of this end point: Endpoint 2, 3, 4, 5, 6, 20: baseline, 14 days, 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 months Endpoint 7: 6, 24, 36 months Endpoint 8: 36 months Endpoint 9: Baseline, 3, 6, 12, 15, 21, 24, 27, 33, 36 months Endpoint 10, 11, 12, 17: baseline, 1, 3, 4, 6, 36 months Endpoint 13, 14, 15: baseline, 1, 3, 6 months Endpoint 16: baseline, 1, 3, 36 months Endpoint 18: baseline, 1, 3 months Endpoint 19: baseline and 36 months Endpoint 21: baseline, 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36	—

Measure

Time frame

Secondary end point(s): 2. Hematological parameters: hgb, hct, erytrocytecount, MCV, differential count, reticulocytes, LDH and URAT 3. Inflammatory parameters and coagulationhemostasis: Ferritin, fibrin D-dimer, ESR, fibrinogen. 4. MPN related symptoms 5. Number of phlebotomies and transfusions. 6. The need for further cytoreductive treatment. 7. Response rates 8. Comparison of the bonemarrow after 3 years with pretreatment bone marrow. 9. CALR and JAK2 mutationburden 10. IgA, IgG, IgM 11. Cholesterol levels 12. YKL-40, myeloperoxidase, beta2-mikroglobulin. 13. markers of for oxidative stress in urine 8-oxoGua, 8-oxoGuo og 8-oxod-Guo. 14. Genexpressionsprofilering, next generation exomsekventering 15. Immunecell studies 16. ROTEM 17. Insulin resistance 18. EndoPat measurements 19. Echocardiografi, heart CT, cerebral blood flow, ultrasound of neck vessels and eye examination 20. Treatment sideeffects 21. Quality of life questionnaires MPN-SAF, BFI og EORTIC QLQ C-30 ;Timepoint(s) of evaluation of this end point: Endpoint 2, 3, 4, 5, 6, 20: baseline, 14 days, 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 months Endpoint 7: 6, 24, 36 months Endpoint 8: 36 months Endpoint 9: Baseline, 3, 6, 12, 15, 21, 24, 27, 33, 36 months Endpoint 10, 11, 12, 17: baseline, 1, 3, 4, 6, 36 months Endpoint 13, 14, 15: baseline, 1, 3, 6 months Endpoint 16: baseline, 1, 3, 36 months Endpoint 18: baseline, 1, 3 months Endpoint 19: baseline and 36 months Endpoint 21: baseline, 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36

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Countries

Denmark

Contacts

Public ContactKFE

Hæmatologisk Afdeling, Sjælland Sygehus, Roskilde

004547324800

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026