Polycythemia Vera

This NIH-sponsored study aims to characterize three biomarkers derived from 129Xe gas exchange MRI and understand how they change in response to interventions. The study focuses on markers derived from the interaction of 129Xe with pulmonary capillary red blood cells RBCs, specifically RBC transfer MRI, cardiogenic oscillations in 129Xe-RBC signal amplitude, and the 129Xe-RBC chemical shift. The study population includes healthy volunteers, patients scheduled to undergo transfusion or phlebotomy, patients with dyspnea, interstitial lung disease ILD, idiopathic pulmonary fibrosis IPF, non-specific interstitial pneumonias NSIP, chronic hypersensitivity pneumonitis cHP, sarcoid, chronic thromboembolic pulmonary hypertension CTEPH, and acute pulmonary embolism.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

Researchers are evaluating the safety, tolerability, and effectiveness of TQB3909 tablets combined with azacitidine in adults with myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndromes. This open, multi-center clinical trial is designed as a Phase IbII study to better understand how this combination treatment works in these blood cancers. Participants receive TQB3909 tablets once daily in 28-day treatment cycles along with azacitidine. The study focuses on monitoring how well patients tolerate the treatment and its effects on their disease. The trial includes assessment of various response rates and survival outcomes over several weeks. Throughout the trial, participants undergo regular evaluations including monitoring for adverse events and laboratory tests for up to 24 weeks. Researchers measure remission rates, duration of remission, and survival outcomes up to 60 weeks. Participants safety and response to treatment are closely tracked during the study.

This research is an international multicenter retrospective observational study focusing on patients with Essential Thrombocythemia ET who are positive for the JAK2V617F mutation. It aims to understand the progression from ET to Polycythemia Vera PV and compare clinical outcomes between those who progressed and those who did not, using criteria defined by the International consensus classification of myeloid neoplasms and acute leukemias from 2022. The study consists of two parts a nested case-control study and a comparative retrospective cohort study. The first part compares ET patients who progressed to PV with matched ET patients who did not progress, based on diagnosis year, age at diagnosis, and disease duration. The second part compares patients diagnosed with de novo PV without prior ET to the ET-to-PV cases, again matched by diagnosis year, age, and disease duration. All patients included in the study were diagnosed by the end of 2020 to allow at least 5 years of follow-up. Participants will have their medical histories reviewed retrospectively to analyze clinical data up to the baseline and at the time of progression. Researchers will assess phenotypic changes and clinical outcomes between groups, with no new treatments or interventions administered. The study is observational and aims to gather information from existing records to better understand disease evolution over time.

Researchers are studying the use of unlicensed cryopreserved cord blood units CBUs for transplantation in both children and adults with blood cancers and other related disorders. This observational study involves patients with hematologic malignancies and various inherited and acquired disorders affecting the blood and immune system. The main goal is to monitor how well neutrophil recovery occurs after transplantation using these unlicensed CBUs in multiple institutions. Participants receive unlicensed cryopreserved CBUs as part of their transplant treatment. The study includes patients of any age receiving these CBUs for approved indications. The protocol focuses on the access and distribution of these unlicensed units rather than a specific treatment intervention. The study gathers data from recipients who receive these CBUs, tracking outcomes after transplantation. Participants are monitored for neutrophil recovery at 60 and 100 days after transplant, defined by a neutrophil count of at least 500mm3. Researchers also collect information on infection transmission, infusion reactions, survival rates at one year, and incidence of acute and chronic graft versus host disease. Platelet recovery is also evaluated. Safety and efficacy outcomes are followed over time to better understand the effects of unlicensed CBUs in this patient population.

Researchers are evaluating AJ1-11095, an oral type II JAK2 inhibitor, in adults with primary myelofibrosis PMF, post-polycythemia vera myelofibrosis PPV-MF, or post-essential thrombocythemia myelofibrosis PET-MF who have not responded to or relapsed after prior treatment with at least one type I JAK2 inhibitor. This phase 1, non-randomized, open-label trial aims to assess the safety, tolerability, pharmacokinetics, clinical activity, and biomarker changes of AJ1-11095 in this patient group. The study includes a dose escalation phase followed by an expansion phase to identify the best dose for future studies.

Researchers are evaluating IM-1021, an antibody-drug conjugate, in a Phase 1 study involving participants with advanced B-cell lymphomas and solid tumors. This first-in-human, open-label study aims to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of IM-1021. The study includes a dose escalation phase to find safe and tolerable doses and an expansion phase to further evaluate these doses in specific cancer types. The study has two parts Part A focuses on escalating doses of IM-1021 given intravenously to determine safety and recommended dosing schedules, including the possibility of alternative dosing. Part B involves expanding participant groups to further test safety and early effectiveness of IM-1021 at doses chosen from Part A. Participants receive the study drug intravenously on an intermittent basis throughout these phases. Participants will undergo multiple assessments including monitoring for treatment-related adverse events, pharmacokinetic blood tests, and evaluations of anti-tumor effects from week 6 until disease progression or study discontinuation. Safety and tolerability will be tracked from the first dose until about 37 days after the last dose. The study duration spans from screening, treatment, and follow-up with data collection continuing up to the study end in 2029.

Researchers are evaluating PRT12396, an investigational oral drug, in participants with high-risk polycythemia vera PV and myelofibrosis MF through a first-in-human, open-label, multi-center Phase 1 study. The study aims to assess the safety, tolerability, pharmacokinetics, and early effects of PRT12396 while determining the maximum tolerated dose and recommended dose for further study. Participants include those diagnosed with PV or MF, including specific subtypes with evidence of disease burden such as splenomegaly. The study is divided into two parts a dose-escalation phase where increasing oral doses of PRT12396 are given twice daily to evaluate safety and identify the best dose levels, followed by a dose-expansion phase where additional participants receive the recommended dose to further assess safety and early efficacy. Capsules are taken twice daily, swallowed whole with water, and may be taken one hour before or two hours after meals. Participants will be involved for an average of about two years, during which researchers will monitor dose-limiting toxicities, adverse events, dose modifications, and pharmacokinetic measures such as blood drug concentration. Other assessments include blood counts, spleen size, symptom scores, and patient global impressions of change. Safety and response outcomes will be tracked throughout the study to guide future research and treatment options.

Researchers are evaluating cytokine induced memory-like natural killer CIML NK cells combined with IL-2 in patients aged 12 years and older who have Acute Myeloid Leukemia AML, Myelodysplastic Syndromes MDS, Myeloproliferative Neoplasms MPN, or Juvenile Myelomonocytic Leukemia JMML that returned after stem cell transplantation. This Phase I clinical trial aims to test the safety and find the appropriate dose for this investigational treatment, which has not been approved by the FDA for relapsed disease. Participants receive intravenous infusions of CIML NK cells on day 0. Before this, patients are given chemotherapy drugs fludarabine daily for three doses starting on day -5 and cyclophosphamide on days -5 and -4 to prepare the body. The study includes both adult and pediatric patients who have relapsed after haploidentical or HLA-matched stem cell transplants. The treatment is followed for safety and response over several weeks. During the study, participants will be monitored closely for safety for six weeks and assessed for treatment response after 28 days. Further follow-ups include checking for leukemia-free survival and overall survival at 100 days and one year, as well as monitoring for acute and chronic graft-versus-host disease over several months to one year. The trial involves regular evaluations including bone marrow tests, blood tests, and clinical assessments to track disease status and side effects throughout participation.

Researchers are evaluating drug combinations to prevent graft-versus-host disease GVHD in people who have received stem cell transplants from unrelated donors with different blood types. This platform protocol focuses on safety and effectiveness of post-transplant cyclophosphamide PTCy based GVHD prevention after mismatched unrelated donor hematopoietic cell transplants in patients with malignant blood diseases. The study compares new drug combinations to a standard treatment. Participants receive one of the drug combinations after transplant, including investigational arms named ACCEL-001 and ACCEL-002, or the shared comparator control group. Conditioning regimens vary and may include combinations of drugs such as busulfan, fludarabine, melphalan, cyclophosphamide, and total body irradiation before transplant. The donor stem cell graft infusion occurs on Day 0, followed by specific post-transplant medications like cyclophosphamide, tacrolimus, mycophenolate mofetil, abatacept, and ruxolitinib, with supportive care for infection prevention and other complications. During the study, participants have regular doctor visits for check-ups and routine tests, complete surveys on physical and emotional health, and provide blood and stool samples. Researchers monitor outcomes including graft-versus-host disease-free, relapse-free survival one year after transplant, infection rates, survival, graft failure, and immune recovery. Safety is closely tracked, including monitoring for cytokine release syndrome and infections. The study lasts for at least one year post-transplant, with detailed data collection on treatment response and side effects.