Active clinical trials for "Primary Myelofibrosis"

The purpose of this study is to investigate the safety, pharmacokinetics (PK) and preliminary efficacy of both the combination of MBG453 and NIS793 with or without decitabine or spartalizumab as well as single agent MBG453 and/or NIS793 single agent in myelofibrosis (MF) subjects post treatment with a Janus Kinase (JAK) inhibitor. In this study, combination therapies with novel agents including immune therapy will focus on determining the promising combinations that provide acceptable safety and efficacy independent of JAK inhibitors. Immune therapy combinations, such as MBG453 in combination with NIS793, might offer the potential to target MF across genetic heterogeneity. The primary objective of this study is to characterize the safety, tolerability and recomended dose for each treatment combination (MBG453 + NIS793, MBG453 + NIS793 + decitabine, and MBG453 + NIS793 + spartalizumab)

To determine the safety of the approach of giving RUXOLITINIB before and after an autologous stem cell transplant, as measured by graft failure or death.

The main purpose of this study is to assess the effects of cyclophosphamide (cytoxan) in the post transplant setting to prevent onset of acute graft-versus-host disease (GVHD). The primary objective is to determine the incidence of grade II-IV acute GVHD following Allogeneic (allo) Hematopoeitic Cell Transplant (HCT) using post-transplant cyclophosphamide (cytoxan) for patients with human leukocyte antigen (HLA) matched unrelated (MUD) and mismatched unrelated (MMUD) donors. Other objectives for this study will be the determination of disease-free survival (DFS) and overall survival (OS) following allo HCT and assess the safety of post-transplant cyclophosphamide (cytoxan) for MUD and MMUD transplantation. Disease recurrence and time to recurrence in patients receiving post-transplant cyclophosphamide compared to historical control without post-transplant cyclophosphamide (cytoxan) will also be evaluated. Other objectives will be to determine the time of onset, severity, responsiveness to treatment, organs involved of acute and chronic GVHD as well as observation of Immune Reconstitution over time.

To evaluate the efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of pacritinib in Asian subjects with myelofibrosis (MF), which includes primary MF (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF).

The purpose of this study is to evaluate the safety and tolerability of captopril and evaluate the effectiveness captopril as measured by changes in the grade of bone marrow scar tissue. The change in spleen size by ultrasound will also be measured.

This phase II trial studies how well PAT-1251 works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. PAT-1251 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

This multicenter, open-label, phase 1 study designed to evaluate safety and tolerability of multi-kinase inhibitor LNK01002 in patients with primary myelofibrosis (PMF), or MF due to polycythemia vera (PV-MF), or essential thrombocythemia (ET-MF), polycythemia vera (PV), or with acute myeloid leukemia (AML).

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 studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose of 400 mg daily was recommended for the phase II studies. Recently, the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy (BAT) in patients with MF was reported at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms. Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells (HSC) without cytotoxicity and subcutaneous (SC) instead of intravenous (IV) administration may avoid high peak levels that can cause apoptosis. Furthermore, the low toxicity associated with low dose decitabine would allow for more frequent (1 to 3 times weekly) administration of the drug which would catch more cells in S-phase via greater exposure time. Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes when combined with pacritinib 400 mg daily.

The Main purpose of this project to study the uptake pattern of FLT-PET and it is value in assessing the malignant hematopoiesis in MPN within the pediatric age group, in terms of diagnosis, staging and monitoring response to therapy. As well as, evaluating FLT-PET as a novel non-invasive technique in cases with MPN and its role in comparison to the standard bone marrow biopsy with regard to disease diagnosis, assessment of disease activity, detection of transformation, monitoring of treatment response and grading of fibrosis.Furthermore, we aim to study the association of FLT-PET uptake patterns with different genetic makeup (JAK2, CALR positive, MPL, or Triple negative disease) or allele burden in cases of Pre-PMF with the ability of FLT-PET to differentiate between Pre-PMF and ET. Although MPNs are diseases of elderly, MPN is diagnosed in younger age groups in a considerable number of cases. Since most of the available data as well as current WHO classification criteria emphases on the "average" MPN patients who range in age between 55 and 65 years. Less consistent data are available in the groups of patients presenting below this median age, such as children and younger adults which we're planning to reveal.

First-line treatment for patients with polycythemia vera, essential thrombocythemia, and pre-myelofibrosis is based on hydroxyurea or pegylated interferon. The objective of treatment is to prevent thrombotic complications and leukemic transformation. Despite overall good response rates, some patients do not respond to treatment and others lose their response over time. Both situations are associated with worse survival and there are to date no clear predictive factors for response although the existence of additional mutations seems unfavorable. In this exploratory study, we hypothesize that biological factors at diagnosis are associated with hematological response at 12 months. We will more specifically study the association between mutational profile, assessed by next-generation sequencing, and cytokine profile with hematological response. This study will help in identifying patients who will not respond to hydroxyurea or pegylated interferon and give the opportunity to try other treatments upfront, in the perspective of precision medicine. On the basic science side, this study will help in understanding the molecular and immunological factors involved in resistance to treatment.