Fanconi Anemia

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 a new combination of evidence-based interventions EBIs aimed at improving diagnostic safety and efficiency in primary care for patients with anemia and decreased glomerular filtration rate. The study is designed as a stepped wedge cluster randomized control trial to measure how these interventions affect patient safety and healthcare efficiency, while also assessing factors influencing their implementation such as acceptability, cost, and sustainability. The study compares an enhanced diagnostic team approach to usual care. The enhanced approach includes automated detection and tracking of abnormal test results, expanding the primary care team to include clinical pharmacists to guide anemia evaluation, and engaging patients through nurse navigators to increase their activation in the diagnostic process. The study involves several clinic groups that receive the intervention at different times, ranging from 12 to 24 months, with some initial control periods. Participants will have their diagnostic accuracy for causes of low hemoglobin and decreased glomerular filtration rate assessed within six months. Researchers will track time to diagnosis, appropriate test usage, treatment costs, and primary care physicians views on the interventions acceptability and feasibility. The study also monitors how well the diagnostic process steps are followed, the interventions reach among patients, and sustainability in clinics over 2.5 years. Patient activation and clinic-level facilitators and barriers are evaluated through surveys and measures during the study period.

Researchers are evaluating whether giving decitabine and filgrastim after allogeneic hematopoietic stem cell transplant HCT is feasible and effective in preventing relapse in children and young adults with acute myeloid leukemia AML, myelodysplastic syndrome MDS, and related myeloid malignancies. This is a phase 2 single-arm pilot study focusing on patients with idiopathic or inherited bone marrow failure syndromes who may have different risks of treatment toxicity. The study is supported by Dana-Farber Cancer Institute philanthropy and institutional grants. Participants will receive cycles of decitabine a nucleoside metabolic inhibitor given by IV infusion and filgrastim a granulocyte colony-stimulating factor given by subcutaneous injection starting between 40 and 120 days after HCT. Treatment cycles last 28 days, with decitabine given on days 2 to 6 and filgrastim on days 1 to 6. Up to six cycles will be given if tolerated. There are two cohorts one with standard risk and one with increased risk for treatment-related toxicities based on inherited bone marrow failure syndromes. After treatment, participants will have follow-up visits every 6 months for 24 months post-HCT. During the study, participants will undergo screening, treatment, and regular follow-up including blood tests and bone marrow biopsies as standard care. Researchers will monitor treatment feasibility by measuring how many complete the treatment cycles, as well as event-free and overall survival up to 24 months. Treatment tolerability will also be assessed. The total participation includes treatment for 6 months plus 24 months of follow-up after transplant to evaluate outcomes and safety.

Researchers are evaluating luspatercept to see if it can improve hemoglobin levels in adults with anemia caused by chronic kidney disease CKD. This study also aims to assess the safety of luspatercept by monitoring side effects in participants. The trial is a phase 2 treatment study sponsored by Memorial Sloan Kettering Cancer Center. Participants will receive luspatercept as a subcutaneous injection once every three weeks. The study does not include a comparison group and focuses on how luspatercept affects hemoglobin levels over time, particularly within 12 weeks and up to week 28. The treatment period is designed to test the effects and safety of the drug in this patient group. During the study, participants will have their hemoglobin levels closely monitored to measure improvements. Researchers will also evaluate other health indicators to ensure safety and effectiveness. The study involves regular visits for treatment and assessment, with the overall participation lasting up to the study completion date in July 2029.

Researchers are evaluating how well elritercept works to improve anemia in adults with myelofibrosis MF who are already taking ruxolitinib. The study compares elritercept to a placebo and aims to see if elritercept can reduce tiredness, improve MF-related symptoms, and help participants perform physical activities more easily. It also looks at elritercepts effects on bone marrow, spleen size, antibody development, and long-term safety. Participants receive either elritercept or a placebo by subcutaneous injection once every 4 weeks during a 36-week double-blinded treatment period. The starting dose of elritercept is 3.75 mgkg, with a possible increase to 5.0 mgkg after the second cycle based on response and safety. After 36 weeks, participants who took placebo may switch to receive elritercept in an extended open-label phase. During the study, participants undergo assessments including blood transfusion independence, symptom and fatigue questionnaires, spleen imaging, and bone marrow evaluation. Researchers monitor safety, antibody formation, and survival for up to 7 years. The main outcome is the proportion of participants who become independent from red blood cell transfusions for at least 12 consecutive weeks during the 36-week treatment. Participants are involved in regular visits and evaluations throughout the treatment and follow-up periods.

Researchers are evaluating elritercept for its ability to reduce the need for red blood cell RBC transfusions and its safety compared to epoetin alfa in adults with very low, low, or intermediate risk myelodysplastic syndromes MDS who require regular blood transfusions. The study aims to understand if elritercept improves tiredness, lowers transfusion burden, enhances quality of life, and elicits an immune response. Participants receive either elritercept or epoetin alfa injections. Elritercept is given as a subcutaneous injection starting at 3.75 mgkg every 4 weeks, with possible dose increases to 5.0 mgkg. Epoetin alfa is administered as a subcutaneous injection starting at 450 IUkg once weekly, with possible dose escalation up to 1050 IUkg. The study follows participants for approximately 5 years to monitor treatment effects and safety. During the trial, participants are regularly assessed for transfusion independence, hemoglobin levels, fatigue, quality of life, and hematological improvements. Researchers monitor blood samples for drug concentration and immune response. Safety is evaluated through medical history, lab tests, and adverse event tracking. The main outcome is the proportion of participants achieving RBC transfusion independence for at least 12 weeks during the first 24 weeks. The study uses questionnaires and clinical assessments to measure fatigue and quality of life.

Researchers are evaluating the efficacy and safety of luspatercept combined with best supportive care compared to placebo with best supportive care in adults with alpha-thalassemia hemoglobin H disease who experience anemia. The study also assesses the safety and drug levels of luspatercept in adolescents with this condition. This phase 2 trial aims to understand how luspatercept affects anemia and transfusion needs in this population. Participants are randomly assigned to one of four groups based on their transfusion dependence status adults who receive luspatercept plus best supportive care, adults who receive placebo plus best supportive care, adolescents who are transfusion dependent receiving luspatercept plus best supportive care, or adolescents who are non-transfusion dependent receiving luspatercept plus best supportive care. The treatments are given on specified days, and participants are monitored for up to 108 weeks, including assessments of drug levels, transfusion burden, hemoglobin changes, and adverse events. Throughout the study, participants undergo regular evaluations including blood tests to measure hemoglobin and transfusion needs, monitoring for side effects, and quality of life assessments. Researchers also track long-term safety outcomes and pharmacokinetics of the drug. The main outcomes include reductions in red blood cell transfusions over 12 to 48 weeks and increases in hemoglobin levels without transfusions. Participants may be followed for up to five years to monitor safety and treatment effects.

Researchers are evaluating APG-5918, an oral drug, to study its safety, how it moves within the body, and its early effects in healthy adults and patients with anemia. This Phase 1 trial aims to find out if APG-5918 is safe and tolerable and to explore dosing levels that might be effective for anemia treatment. The study includes healthy volunteers and patients with anemia, including those with beta-thalassemia and related conditions. The trial has two parts. Part A randomly assigns healthy volunteers to receive a single dose of APG-5918 or a placebo in a double-blind manner, with dose levels increasing across up to seven groups. Part B involves an open-label, multi-dose approach where anemic patients receive daily APG-5918 for 84 days or until treatment end. The study monitors safety, tolerability, drug levels in the blood, and preliminary effects on hemoglobin. Participants will undergo assessments including blood tests to measure drug concentration and hemoglobin levels, and monitoring for any adverse events up to 7 days in Part A and 84 days or until treatment end in Part B. The trial includes physical exams, lab tests, and ECGs to ensure safety. Total participation duration varies, with regular visits to assess how well the drug is tolerated and its early effects on anemia.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of an anti-GPRC5D CAR-T cell product called OriCAR-017 in adults with relapsed or refractory multiple myeloma. This Phase III open-label study is the first clinical trial of OriCAR-017 in the United States by OriCell Therapeutics Co., Ltd., aiming to find suitable dosing and assess early treatment results in this patient group. The study includes a Phase I dose escalation stage with three different doses given as a single intravenous infusion to up to 18 participants. This is followed by a dose expansion stage with 10-15 participants and then a Phase II stage that may include up to 48 participants. Each participant receives one infusion of OriCAR-017 to evaluate its effects and safety. Participants will be closely monitored for up to two years after treatment. Researchers will assess the maximum tolerated dose and dose-limiting toxicities within 28 days after infusion. They will also study how the drug moves through and affects the body, measure response duration, progression-free survival, overall survival, and other response rates. Regular evaluations include laboratory tests, clinical assessments, and safety monitoring throughout the study period.