Ruxolitinib in Patients With Myelofibrosis

Sponsor
Assiut University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05762874
Collaborator
(none)
51
27

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase

Detailed 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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
51 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Safety and Effectiveness of Ruxolitinib in Patients With Myelofibrosis
Anticipated Study Start Date :
Mar 1, 2023
Anticipated Primary Completion Date :
Mar 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Outcome Measures

Primary Outcome Measures

  1. decrease of spleen size [6 months]

    the proportion of patients achieving ≥50% reduction in Spleen size

  2. symptoms burden [6 months]

    change in the burden of the constitutional symptoms assessed by the MF Symptom Assessment Form on a scale of 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be)

Secondary Outcome Measures

  1. adverse events of Ruxolitinib on myleofibrosis patients according to WHO criteria of drug toxicity [1 year]

    Anemia,leucopenia and thrombocytopenia in complete blood count and reactivation of hepatitis (B,C) virus by PCR

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Inclusion Criteria:
  • PMF was diagnosed according to the 2016 revised International Standard Criteria, and PPV-MF or PET-MF according to standard criteria with JAK2 positive mutation , palpable spleen (≥5 cm below the left costal margin, measured using a soft ruler during quiet respiration), high-risk and intermediate-2 risk PMF, PPV-MF or PET-MF with disease-related symptoms or symptomatic splenomegaly and patients with intermediate-1 risk PMF, PPV-MF or PET-MF who have symptoms not controlled with supportive therapies or symptomatic splenomegaly .

  • patients who previously started Ruxolitinib and still taking it .

Exclusion Criteria:
  • low risk MF patients

  • intermediate risk 1 without splenomegaly or symptoms

  • JAK2 negative mutation

  • inadequate bone marrow reserve at baseline visit, as demonstrated by at least 1 of the following: absolute neutrophil count (ANC) ≤1 × 109/l, platelet count <50 × 109/l, without the assistance of growth factors, thrombopoietic factors or platelet transfusions, and Hb ≤6.5 g/dl despite transfusions

  • severely impaired renal function (defined by creatinine clearance less than 30 ml/min); inadequate liver function (total bilirubin ≥2.5 × upper limit of normal [ULN] and subsequent determination of direct bilirubin ≥2.5 × ULN or alanine aminotransferase >2.5 × ULN or aspartate aminotransferase >2.5 × ULN

  • acute viral hepatitis or active chronic hepatitis B or C infection

  • concurrent treatment with a potent systemic inhibitor or inducer of CYP3A4

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Assiut University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Marwa Ali Mahmoud Hassan, principle investigator, Assiut University
ClinicalTrials.gov Identifier:
NCT05762874
Other Study ID Numbers:
  • myelofibrosis
First Posted:
Mar 10, 2023
Last Update Posted:
Mar 10, 2023
Last Verified:
Feb 1, 2023
Studies a U.S. FDA-regulated Drug Product:
Yes
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 10, 2023