Topics

Myelofibrosis Treated With Pacritinib Before aSCT. (HOVON134MF)

2018-08-28 21:53:14 | BioPortfolio

Summary

The only curative treatment for patients with myelofibrosis (MF) is allogeneic stem cell transplantation (SCT). Treatment with JAK2 inhibitors like pacritinib improves condition of MF patients, decreases spleen size and might diminish graft-versus-host disease (GvHD), thereby improving the outcome of SCT.

Description

Despite recent new therapeutic options, allogeneic Stem Cell Transplantation remains the only curative option in patients with Myelofibrosis. Therefore, optimalization of this therapy remains a major challenge. Improvement of the clinical condition of these patients, decreasing spleen size can be accomplished by JAK2 inhibitor treatment and might improve SCT outcome. In addition, selective JAK2 inhibitors might modulate GvHD which can also add to improved SCT outcome. Also, decreasing the burden/activity of the disease before allo-SCT might also improve final disease response. The first, limited, clinical data of ruxolitinib treatment before allo-SCT show controversial effects on the outcome of SCT. Therefore, additional prospective clinical trials have to be done to establish the role of JAK2 inhibition before allogeneic SCT. Since ruxolitinib has considerable myelosuppressive effects which might limit the clinical use in some MF patients, other selective JAK2 inhibitors might be useful in this setting. Pacritinib, as a JAK2/FLT3 inhibitor, has a very potent JAK2 inhibitory activity without myelosuppressive effects and might therefore be more suitable than ruxolitinib. The major possible side effects are gastro-intestinal and can be managed with medication. In several studies, pacritinib has shown to be effective in decreasing spleen size and has shown to improve clinical condition of patients. Therefore, this compound seems promising in improving the outcome of allo-SCT. Although pacritinib causes no inhibition of JAK1 activity and therefore might have limited effects in decreasing inflammatory response, this might also be of benefit since a "withdrawal syndrome" as has been described after cessation of ruxolitinib is not to be expected.

With this trial, using pacritinib treatment before allo-SCT, the issue of improvement of SCT outcome will be investigated.

Study Design

Conditions

Myelofibrosis

Intervention

Pacritinib

Location

ZNA
Antwerpen
Noord-Holland
Belgium
3000 CA

Status

Recruiting

Source

Stichting Hemato-Oncologie voor Volwassenen Nederland

Results (where available)

View Results

Links

Published on BioPortfolio: 2018-08-28T21:53:14-0400

Clinical Trials [97 Associated Clinical Trials listed on BioPortfolio]

A Phase II Non-Controlled, Open-Label, Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Study of Pacritinib in Myelofibrosis

To evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of pacritinib in Asian subjects with myelofibrosis (MF), which includes primary MF (PMF), post-polycythemi...

Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia

The primary hypothesis of the study is that treatment with either once-daily or twice-daily pacritinib results in a greater proportion of patients with thrombocytopenia and myelofibrosis a...

Determine Pacritinib Pharmacokinetics in Impaired Hepatic Patients and Healthy Subjects

This is an open-label, parallel-group, single-dose study of the PK and safety of 400 mg pacritinib administered orally to patients with stable chronic liver disease and healthy control sub...

Pacritinib Combined With Decitabine or Cytarabine in Older Patients With AML

The purpose of this study is to see if a medicine called pacritinib is both safe and effective as a study intervention for patients with AML in combination with either decitabine or cytara...

Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)

For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I ...

PubMed Articles [47 Associated PubMed Articles listed on BioPortfolio]

Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2/FLT3 inhibitor, and chemotherapy in FLT3-ITD-positve AML.

Activating FLT3 internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) associate with inferior outcomes. We determined that pacritinib, a JAK2/FLT3 inhibitor, has in vitro ac...

The evolving understanding of prognosis in post-essential thrombocythemia myelofibrosis and post-polycythemia vera myelofibrosis vs primary myelofibrosis.

Myelofibrosis (MF) is the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In some patients with essential thrombocytopenia or polycythemia vera, wh...

Reduced intensity allogeneic stem cell transplantation for younger patients with myelofibrosis.

Allogeneic stem cell transplantation (alloSCT) is a curative procedure for myelofibrosis. Elderly people are mainly affected, limiting the feasibility of myeloablative regimens. The introduction of re...

GATA-1 a potential novel biomarker for the differentiation of essential thrombocythaemia and myelofibrosis.

The BCR-ABL negative myeloproliferative neoplasms, polycythaemia vera, essential thrombocythaemia (ET) and myelofibrosis (MF) are characterised by mutations in JAK2, CALR or MPL. However, a yet unknow...

WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis.

Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of d...

Medical and Biotech [MESH] Definitions

A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.

An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.

A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.

More From BioPortfolio on "Myelofibrosis Treated With Pacritinib Before aSCT. (HOVON134MF)"

Quick Search

Relevant Topics

Stem Cells
Track and monitor developments in stem cell research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry.  BioPort...

Transplantation
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...


Searches Linking to this Trial