Ruxolitinib in Patients With Myelofibrosis

February 28, 2023 updated by: Marwa Ali Mahmoud Hassan, Assiut University

Safety and Effectiveness of Ruxolitinib in Patients With Myelofibrosis

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

51

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients who are attending clinical hematology unit and clinic in Assiut university are evaluated for:

  1. diagnosis (before start of treatment for naive patients)
  2. if confirmed diagnosis (for naive and previously diagnosed patients)

  3. follow up at (3,6,12 months) by

    • CBC
    • spleen size
    • symptoms burden according to MF-SAF (symptom assessment form)
    • Transfusion demand
    • dosage adjustment, treatment duration and discontinuation rates
  4. Adverse events of the drug mainly hematological cytopenia according to WHO criteria of drug toxicity and hepatitis infection or reactivation

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
decrease of spleen size
Time Frame: 6 months
the proportion of patients achieving ≥50% reduction in Spleen size
6 months
symptoms burden
Time Frame: 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)
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
adverse events of Ruxolitinib on myleofibrosis patients according to WHO criteria of drug toxicity
Time Frame: 1 year
Anemia,leucopenia and thrombocytopenia in complete blood count and reactivation of hepatitis (B,C) virus by PCR
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2023

Primary Completion (Anticipated)

March 1, 2025

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

February 11, 2023

First Submitted That Met QC Criteria

February 28, 2023

First Posted (Estimate)

March 10, 2023

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

February 28, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • myelofibrosis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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