Fanconi Anemia

Researchers are studying biomarkers from 129Xe gas exchange MRI to understand how they change with different medical interventions. The study focuses on interactions between 129Xe and red blood cells in the lungs. Participants include healthy volunteers and patients with conditions like interstitial lung disease, pulmonary hypertension, acute or chronic pulmonary embolism, anemia, polycythemia, and dyspnea. The study uses hyperpolarized xenon gas inhaled in multiple doses followed by breath holds, alongside oxygen administration. Participants are grouped by treatment: those undergoing transfusion or phlebotomy, patients receiving oxygen for lung-related conditions or healthy volunteers, and those recently diagnosed with acute or chronic pulmonary embolism. Treatments and responses are monitored at baseline and various follow-up points. Participants will undergo MRI scans to measure red blood cell transfer, chemical shifts after oxygen delivery, and changes in red blood cell signal oscillations before and after treatment. The study includes visits up to 3–6 months after interventions to track changes. Researchers also monitor safety and participant adherence throughout the study, which lasts until mid-2028.

Researchers are conducting the GENESIS clinical study to map the HLA genomic region in the Greek population and explore its possible links with various underlying diseases. This non-interventional, multicenter study aims to provide a pilot map of genetic variation in HLA that may be useful in medical research and clinical applications related to selected diseases. The study plans to include 12,000 participants over a total duration of 36 months. Each participant will attend one visit at a participating site during which they will provide demographic data, lifestyle information such as smoking and alcohol use, blood pressure measurements, details on diagnosed diseases and treatments, and recent laboratory test results if available. Buccal swab samples will be collected from each participant to extract DNA for HLA genotyping analysis. Selected samples will undergo further whole genome sequencing to investigate associations with autoimmune diseases. Participants will receive a personalized ancestry report after analysis completion. During the study visit, data collection includes demographic and health information, as well as laboratory and clinical test results from the past year. The genetic material from buccal swabs will be stored and processed for genetic analysis. Researchers will measure allele frequency of HLA alleles in the Greek population and assess the prevalence and risk associations of selected HLA-related diseases. The study's total duration is 36 months with results available at the end of this period.

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 intervention's acceptability and feasibility. The study also monitors how well the diagnostic process steps are followed, the intervention's 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 elritercept compared to epoetin alfa to treat anemia in adults with very low, low, or intermediate risk myelodysplastic syndromes (MDS) who need regular red blood cell (RBC) transfusions. The study aims to assess how elritercept affects the need for RBC transfusions, its safety, and whether it improves tiredness and quality of life compared to epoetin alfa. The trial also explores the immune response to elritercept and monitors medical problems related to the treatment. Participants will be randomly assigned to receive either elritercept or epoetin alfa. Those receiving elritercept will start with a dose of 3.75 mg/kg by subcutaneous injection every 4 weeks, which may be increased to 5.0 mg/kg if necessary. Participants receiving epoetin alfa will start at 450 IU/kg by subcutaneous injection once weekly, with possible dose escalation up to 1050 IU/kg. Treatment will continue with monitoring over several cycles, each lasting 28 days, with assessments up to 48 weeks and potential follow-up to about 5 years. During the study, participants will have regular visits to assess their need for RBC transfusions, hemoglobin levels, fatigue using the FACIT-Fatigue Scale, quality of life through questionnaires, and blood tests to monitor drug levels and immune response. The main outcome is the proportion of participants who become independent of RBC transfusions for at least 12 consecutive weeks with improved hemoglobin. Safety and overall health will be closely monitored, including tracking any progression to acute myeloid leukemia or death. The total participation duration may last up to several years to evaluate long-term effects.

Researchers are evaluating the efficacy and safety of luspatercept combined with best supportive care (BSC) compared to placebo plus BSC for treating anemia in adults with alpha-thalassemia hemoglobin H (HbH) disease. The study also aims to assess the safety and drug levels of luspatercept in adolescent participants. This Phase 2 trial is sponsored by Bristol-Myers Squibb and focuses on improving anemia management in this specific patient group. Participants are divided into groups based on transfusion dependence and age. Adult transfusion-dependent and non-transfusion-dependent participants receive either luspatercept plus BSC or placebo plus BSC. Adolescent participants aged 12 to under 18 years are assessed for safety and pharmacokinetics of luspatercept. Treatments involve specified doses given on designated days, with monitoring across several weeks. The study includes a randomized, quadruple-masked design to compare outcomes effectively. During the study, participants undergo regular assessments including blood tests to measure hemoglobin levels, red blood cell transfusion requirements, and adverse events. Researchers also monitor pharmacokinetics and immunogenicity over extended periods up to several years. Patient-reported outcomes, quality of life, physical function tests, and biomarkers related to anemia and iron homeostasis are evaluated to understand treatment impact. The total participation may last up to 8.5 years, ensuring comprehensive safety and efficacy data collection.

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 I/II 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.

Researchers are evaluating the safety and clinical activity of different doses of belantamab mafodotin combined with lenalidomide, dexamethasone, and nirogacestat in patients with newly diagnosed multiple myeloma who are not able to undergo a transplant. This phase 1/2, open-label study aims to find the recommended dose for future studies and to explore how to manage eye-related side effects. About 36 participants will be enrolled, with follow-up lasting up to 3 to 4 years after enrollment ends. Belantamab mafodotin is given intravenously every other 28-day cycle at doses ranging from 1.0 to 1.9 mg/kg. Lenalidomide is taken orally daily on days 1 to 21 of each 28-day cycle. Dexamethasone is given either orally or intravenously on days 1, 8, 15, and 22 of each cycle, with dose adjustments based on age. Nirogacestat is taken twice daily starting three days before the first dose and on the same days as belantamab mafodotin. The study has two parts: dose finding to establish the best dose, followed by dose expansion with random assignment to different dose modification guidelines for eye side effects. Participants will undergo regular assessments to monitor side effects, including eye exams, and overall response to treatment. Researchers will track dose-limiting toxicities, adverse events, ocular toxicity, and response rates over up to four years. Additional evaluations include measuring drug levels, disease progress, and survival. Participants must provide consent and will be closely monitored throughout the study period, which is expected to last approximately four years in total.

Researchers are evaluating AMXI-5001, an oral drug that blocks PARP and microtubule polymerization, in adults with advanced cancers that have not responded to other treatments. This Phase I/II trial aims first to find the best dose and then to study the drug's safety and effects in more detail. The study includes participants with several types of advanced cancers, including breast, ovarian, prostate, pancreatic, and other malignant tumors. The trial has two parts: Phase I involves dose escalation, where up to 70 participants receive AMXI-5001 orally twice a day with food on a weekly continuous 7-day schedule, with each treatment cycle lasting 28 days. After determining the recommended dose, Phase II will enroll up to 52 participants to further assess safety, drug levels in the blood, and anti-tumor activity using the chosen dose. All participants receive the study drug as monotherapy. Participants will be monitored for safety, drug concentration in plasma, and tumor response using standard imaging and laboratory tests over approximately 24 months. The primary goals include finding the maximum tolerated dose and recommended dose for Phase II, as well as characterizing the safety profile. Participants must consent and meet eligibility criteria related to their cancer status and overall health. The trial will continue until about October 2026.