Active clinical trials for "Myeloproliferative Disorders"

This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).

This phase II trial studies how well donor atorvastatin treatment works in preventing severe graft-versus-host disease (GVHD) after nonmyeloablative peripheral blood stem cell (PBSC) transplant in patients with hematological malignancies. Giving low doses of chemotherapy, such as fludarabine phosphate, before a donor PBSC transplantation slows the growth of cancer cells and may also prevent the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also cause an immune response against the body's normal cells (GVHD). Giving atorvastatin to the donor before transplant may prevent severe GVHD.

This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring grade II-IV acute graft-versus-host disease (GVHD). In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged pharmacologic immunosuppression.

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.

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.

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.

Classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a family of clonal chronic hematologic malignancies that include. polycythemia vera (PV), essential thrombocythemia (ET), and primary. Myelofibrosis (MF) . The classic MPNs historically have predominantly been diagnosed in older adults, with a median age at diagnosis of 60-72 years . Adults less than 40 years of age make up a largely underrepresented and therefore less studied subset of patients constituting 2.2-6.6% of yearly MPN cases in population- based study. These estimates are lower than incidence rate among patients between 40 and 49 years of age (9.1-10%), and have remained largely unchanged over the past four decades . However, with increasing trends in MPN incidence consequent to increased diagnostic recognition, better pathobiologic understanding, and more frequent JAK2/CALR/MPL mutational testing and newly revised WHO diagnostic criteria, it is conceivable that MPNs may be diagnosed at a higher frequency, in the younger patients, over time.

The purpose of this study is to determine whether cyclophosphamide post bone marrow transplant increases the rate of patients alive, in remission and without immunosuppression, one year after transplant, when compared with the combination of methotrexate and calcineurin inhibitor

Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal factor determining patients' survival in MPN. In recent years, DNA methylation has appeared as a mean to measure aging via the development of epigenetic clocks that have also been associated with the occurrence of thrombosis and cancer. The epiC project aims at determining epigenetic age of MPN patients and search for an association between this parameter and thrombotic/hematological complications.

Ambispective, national, multicenter observational cohort study aimed at characterizing the satellite dysimmune manifestations of clonal hematopoiesis, including Vexas (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome.