Evaluation of Atorvastatin as an Adjuvant Therapy in Philadelphia-Negative Myeloproliferative Neoplasms: Impact on Inflammatory Markers and Cell Counts

The primary objective of this study is to evaluate the effect of adjuvant treatment with **atorvastatin** in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) who are undergoing Best Available Therapy (BAT). This will be assessed by measuring inflammatory markers and cell counts. Understanding the impact of atorvastatin on these parameters is clinically relevant as it may offer insights into additional therapeutic benefits for managing MPNs, potentially improving patient outcomes by reducing inflammation and modulating disease activity.

Secondary objectives include:

• Assessing biochemical markers for inflammation and disease burden in MPN patients during statin treatment, and evaluating their relationship to symptom development, thrombosis, and transformation to myelofibrosis and acute myeloid leukemia (AML).
• Evaluating the thrombophilia profile in MPN patients before and during atorvastatin treatment.
• Assessing the number and functionality of circulating immune cells before and during atorvastatin treatment.
• Investigating the effect of statins on the gut microbiome and possible correlations with treatment response.

The clinical trial involves participants diagnosed with **blood cancer**, specifically those with WHO 2016 classified essential thrombocythemia (ET), polycythemia vera (PV), or prefibrotic primary myelofibrosis (prePMF) exhibiting thrombocytosis and/or leukocytosis. The study population includes both male and female subjects over the age of 18, with an expected survival of more than three years. Participants must not have been on statin therapy prior to the trial and, if receiving ongoing cytoreductive treatment, it must have commenced more than three months prior with no anticipated changes in dosage or treatment type within the next year. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the effect of **atorvastatin** as an adjuvant treatment in patients with Philadelphia-negative chronic myeloproliferative neoplasms, including essential thrombocytosis, polycythemia vera, and prefibrotic myelofibrosis. This is a Phase 4, randomized, double-blind, controlled trial. The trial aims to assess the impact of atorvastatin on inflammatory markers and cell counts in patients undergoing Best Available Therapy (BAT). The trial is expected to commence recruitment on December 2, 2024, and conclude by December 2, 2027, with a maximum treatment period of 24 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as WHO 2016 classification of the disease, age over 18 years, and an expected survival of more than three years. The screening will ensure that participants are not currently on statin therapy and have stable ongoing cytoreductive treatment. Following the screening, participants will be randomized to receive either atorvastatin or a placebo, administered orally in the form of film-coated tablets. The primary endpoint will focus on changes in inflammatory parameters, including hs-CRP, inflammatory cytokines, leukocyte count, platelet count, and neutrophil/lymphocyte ratio (NLR).

Throughout the trial, participants will attend regular follow-up visits to monitor their response to the treatment and any adverse effects. These visits will include assessments of the primary and secondary endpoints, as well as safety evaluations. The end-of-study visit will occur at the conclusion of the 24-month treatment period or upon early termination. Conditions that may lead to early termination from the study include significant adverse reactions, withdrawal of consent, or any changes in the participant's health status that contraindicate continued participation. The expected length of participant involvement is up to 24 months, contingent upon adherence to the study protocol and absence of any exclusionary conditions.

The clinical trial involves the administration of **Atorvastatin** in three different dosages: 20 mg, 40 mg, and 80 mg, all in the form of film-coated tablets. These tablets are manufactured by Pinewood Laboratories Limited and are intended for **oral use**. The active substance in each tablet is atorvastatin, a chemical compound classified under the ATC code C10AA05. The maximum daily dose for each formulation is 80 mg, with a total maximum dose of 13,440 mg over the treatment period. The treatment period is set to a maximum of 24 months. The tablets are not formulated for pediatric use and are not classified as orphan drugs.

Participants in the trial will receive one of the atorvastatin dosages as an adjuvant treatment alongside their Best Available Therapy (BAT) for Philadelphia-negative chronic myeloproliferative neoplasms, which include essential thrombocythemia, polycythemia vera, and prefibrotic myelofibrosis. The primary objective is to assess the effect of atorvastatin on inflammatory markers and cell counts in these patients. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by evaluating the impact of adjuvant treatment with **atorvastatin** on patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) who are undergoing Best Available Therapy (BAT). The primary endpoints for efficacy assessment include inflammatory parameters such as high-sensitivity C-reactive protein (hs-CRP), inflammatory cytokines, leukocyte count, platelet count, and the neutrophil/lymphocyte ratio (NLR). These parameters will be measured to determine the effect of atorvastatin on inflammation and cell counts in the patient population.