Ruxolitinib in Patients With Myelofibrosis

Myelofibrosis Clinical Trial

Official title: Safety and Effectiveness of Ruxolitinib in Patients With Myelofibrosis

Status Not yet recruiting

Clinical Trial Summary

Prospective study to evaluate the response of myelofibrosis patients to ruxolitinib and it's adverse events on patients (1 year observational study).

Clinical Trial Description

Myelofibrosis (MF) is a clonal disorder of the pluripotent hematopoietic stem cell in which the abnormal stem cell population releases several cytokines and growth factors into the bone marrow microenvironment, it is pathologically characterized by bone marrow fibrosis, extramedullary hematopoiesis, and an overactive Janus kinase/signal transducers and activators of transcription( JAK-STAT) pathway, MF is estimated to have an annual incidence of 0.47-1.98 per 100,000, Most patients are aged > 60 years at initial diagnosis tends to be more common in males than females, It may be de novo (primary MF) or secondary to polycythemia vera (PV) or essential thrombocythemia (ET).

Most patients present with anemia, splenomegaly, and constitutional symptoms, but up to 30% of patients are asymptomatic at diagnosis, symptomatic patients develop Splenomegaly-related symptoms such as abdominal distension and pain, early satiety, dyspnea, together with constitutional symptoms such as fatigue, night sweats, cachexia, pruritus, bone pain, weight loss, and fever are the dominant aspects of the clinical picture heavily affecting the functional status and quality of life (QoL) of MF patients, the most frequent cause of death is the evolution to acute myeloid leukemia, also other conditions such as progression without transformation, cytopenia-related complications and cardiovascular events may be fatal.

Approximately 90% of patients with MF carry mutations in any of 3 driver genes: Janus kinase 2 (JAK2) in ~ 60% of cases, calreticulin (CALR) in ~ 20%, and myeloproliferative leukemia virus oncogene (MPL) in ~ 10%, Mutant proteins activate the (JAK-STAT) pathway and other pathways downstream leading to myeloproliferation, proinflammatory cytokine expression, and bone marrow remodeling.

Current diagnosis of PMF is based on the 2016 WHO-criteria and involves a composite assessment of clinical and laboratory features, Prognosis is currently based on three different scoring systems (IPSS, DIPSS, DIPSS PLUS) and recently mutations were considered in the development of three new prognostic models in PMF.

At present the only curative treatment for MF is allogeneic stem cell transplantation. Most patients with MF are considered ineligible for transplantation because of age or comorbidities, so treatment for the majority of patients is focused on symptom control.

Since the discovery of the JAK2 mutations and the development of JAK inhibitors have significantly changed the therapeutic outcome of MF as far symptoms control and patients' QoL are concerned, In this article, we present our recommendations for the practical management of MF with ruxolitinib a Janus kinase (JAK1/JAK2) inhibitor approved by the European Medicines Agency for the treatment of disease-related splenomegaly or symptoms in adult patients with primary MF , post-polycythemia vera MF , and post-essential thrombocythemia MF, and by the US Food and Drug Administration for intermediate or high-risk MF, including PMF, PPV-MF, and PET-MF. ruxolitinib therapeutic effect was not limited to Spleen volume response, being also efficacious in relieving constitutional symptoms; reducing abdominal discomfort, appetite loss, itching, fatigue, night sweats; and improving QoL. The main toxicity of ruxolitinib is hematological due to the non-selective inhibition of JAK-STAT signaling, an essential pathway for normal hematopoiesis, Due to its impairing activity on immune response, ruxolitinib may favor an increased incidence of both opportunistic and non-opportunistic infections .Few studies evaluate the role of ruxolitinib in MF and it's role in improving the patient's QoL in Assiut university so we decided to perform this influential study to assess the effectiveness of ruxolitinb in MF and it's adverse events on MF patients. ;

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

• NCT number: NCT05762874
• Study type: Observational
• Source: Assiut University
• Contact: Marwa Ali Mahmoud, specialist
• Phone: 01002085973
• Email: meroooo17789@gmail.com
• Status: Not yet recruiting
• Start date: March 2023
• Completion date: June 2025