Neutropenia

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 studying a rare genetic condition called WHIMS, which causes severe neutropenia, a low white blood cell count that makes it harder for the body to fight infections. WHIMS leads to serious infections and complications like warts and cancers related to human papillomavirus (HPV). This research aims to evaluate the safety and effectiveness of a drug called Mozobil in treating neutropenia in people with WHIMS, exploring doses within the approved range. Participants will receive Mozobil through twice daily subcutaneous injections or continuous infusion using a pump. The study includes a dose escalation phase where doses increase over five days until white blood cell counts improve or the maximum dose is reached. After this, patients may enter a long-term phase receiving Mozobil once or twice daily for up to five years. Treatment will be paused for two days before starting Mozobil if participants are on certain white blood cell stimulating medications. During the study, participants will undergo medical history reviews, physical exams, lung and heart function tests, and blood and urine sampling to monitor safety and effectiveness. Researchers will track white blood cell levels, infection rates, and HPV-related skin lesions. Participants will also provide samples for further analysis and adhere to contraception requirements if applicable. The study may last up to seven years, with ongoing safety and response monitoring throughout.

Researchers are evaluating the safety and effectiveness of emapalumab to treat prolonged severe cytopenia in participants with large B-cell lymphoma (LBCL) who have received CAR T-cell therapy (CART). This pilot study aims to assess how well emapalumab works and its safety, while also exploring biomarkers that might show how participants respond or resist the treatment. The study is a Phase 2 interventional trial sponsored by M.D. Anderson Cancer Center. Participants will receive emapalumab by infusion and be assigned to one of two dose levels. Around 16 to 32 participants will be enrolled across these doses. The trial follows a stepwise approach: if enough participants show improvement at a dose level, the dose is considered effective, and the study may test a higher dose following the same approach. Dosing and enrollment continue based on participants' blood test improvements after treatment. During the study, participants will undergo blood tests and safety monitoring for about one year. Researchers will check for adverse events and evaluate the treatment's impact on blood cell counts. Bone marrow biopsies will be performed before and after each treatment cycle and if severe cytopenia recurs. Participants will also be monitored for infections and organ function. The total involvement includes screening, treatment, and follow-up visits to assess treatment effects and safety.

Researchers are evaluating the effectiveness and safety of using Trilaciclib to prevent chemotherapy-related myelosuppression in patients with Ewing's sarcoma who have not previously received systemic anti-tumor treatment. This is a phase 2, prospective, randomized, controlled clinical trial focusing on patients aged 14 to 40 years with confirmed Ewing's sarcoma. The study compares the use of Trilaciclib combined with standard VDC+IE chemotherapy versus chemotherapy alone. Participants will be randomly assigned to one of two groups: the experimental group receiving Trilaciclib along with alternating VDC+IE chemotherapy every 3 weeks for up to 17 cycles, or the control group receiving only the alternating VDC+IE chemotherapy on the same schedule. The chemotherapy regimen includes vincristine, doxorubicin (or actinomycin D after a certain cumulative dose), cyclophosphamide, ifosfamide, and etoposide. Trilaciclib is given as an intravenous infusion following chemotherapy administration in the experimental group. Supportive care is allowed in both groups as needed. During the treatment, participants will be monitored for myelosuppression effects such as neutropenia and thrombocytopenia through laboratory tests. The primary outcome measures how long severe neutropenia lasts in the first treatment cycle, with additional outcomes tracking recovery times, incidence of febrile neutropenia, anemia, and serious infections across multiple cycles. The study will also assess event-free survival up to 24 months. Treatment continues until disease progression, unacceptable side effects, or withdrawal. The total study duration includes up to 17 cycles of treatment and follow-up assessments.

Researchers are studying the safety and tolerability of elritercept in adults with anemia linked to very low, low, or intermediate risk Myelodysplastic Syndromes (MDS). The study aims to understand how elritercept affects red blood cell production and the progression of MDS, including how well participants tolerate different doses of the drug. This phase 2, open-label trial focuses on anemia associated with lower-risk MDS and evaluates the impact on healthy red blood cell production. Participants receive elritercept as a subcutaneous injection every 4 weeks, with doses ranging from 0.75 mg/kg to 5.0 mg/kg during an initial period of up to 4 cycles (each 28 days). Following this, participants continue treatment with elritercept every 4 weeks for up to 24 cycles, with dose adjustments based on individual response. Different cohorts include participants with or without ring sideroblasts, those requiring red blood cell transfusions, and those with chronic myelomonocytic leukemia (CMML). Some participants may enter a long-term extension phase receiving elritercept every 4 weeks for up to about 10 years. During the study, participants undergo regular monitoring including blood tests, assessments of red blood cell parameters, and tracking of adverse events and disease progression. Researchers measure treatment-emergent adverse events, progression to higher-risk MDS or acute leukemia, transfusion independence, and hematologic improvements over up to 11 years. The study includes follow-ups to evaluate the duration and timing of responses, safety, and overall effects on anemia and MDS progression.

This research aims to evaluate whether starting treatment with emapalumab can improve treatment planning and increase the effectiveness of standard therapies for pediatric patients with severe aplastic anemia (sAA). The study focuses on children and young adults under 25 years old who have been newly diagnosed with sAA characterized by severe cytopenias and hypocellular bone marrow. The trial is sponsored by Memorial Sloan Kettering Cancer Center and funded by the FDA's Office of Orphan Products Development. Participants will initially receive emapalumab, an antibody that blocks interferon gamma, for six weeks. After this initial treatment, they will either receive standard immunosuppressive therapy (IST) with equine anti-thymocyte globulin and cyclosporin along with a reduced dose of emapalumab, or they will proceed to a standard hematopoietic stem cell transplant (HCT). These two treatment paths are both experimental arms within the study. During the study, participants will be closely monitored to assess their response to treatment at six weeks. Evaluations include clinical assessments and laboratory tests to measure blood counts and marrow function. Researchers will track the best response to therapy and monitor safety throughout the process. The total study duration and follow-up extend up to May 2029, allowing for long-term observation of outcomes.

Researchers are studying the effects of mavorixafor in people aged 12 and older who have congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders. These disorders cause low levels of neutrophils, a type of white blood cell, leading to recurrent or serious infections. The study aims to show if mavorixafor can increase neutrophil levels and reduce infections, while also evaluating the drug's safety and how well participants tolerate it. Participants will continue their current treatments, which may include granulocyte-colony stimulating factor (G-CSF), immunoglobulin replacement therapy, prophylactic antibiotics, or no active treatment. They will be randomly assigned to receive either mavorixafor or a placebo once daily by mouth for 52 weeks. The study is double-blind, meaning neither participants nor researchers will know which treatment is given until the study ends. Throughout the study, participants will be monitored for infections and neutrophil counts, with assessments including infection rates reviewed by a blinded committee. Other measures include infection severity, duration, antibiotic use, presence of oral ulcers, and fatigue levels from patient questionnaires. The research team will track safety and tolerability during the 52-week treatment period, with follow-up assessments to observe outcomes and any side effects.

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.

This research aims to improve antibiotic treatment for children with cancer who develop febrile neutropenia, a condition where fever occurs alongside a low white blood cell count due to chemotherapy. This condition often requires broad-spectrum antibiotics to fight bacterial infections. However, some children experience faster kidney clearance of antibiotics (augmented renal clearance), which may reduce antibiotic levels and affect treatment effectiveness. The study focuses on two antibiotics, piperacillin-tazobactam and meropenem, to see if adjusting doses based on kidney function can improve outcomes. Participants will be divided into three groups based on kidney function and treatment: children with normal or low kidney function receiving standard antibiotic doses, children with increased kidney function randomly assigned to either standard doses or higher adjusted doses. Blood tests will be done to estimate kidney function and therapeutic drug monitoring will be performed regularly to measure antibiotic levels and adjust doses as needed. The study uses a randomized design and includes monitoring drug concentrations and adjusting doses to reach target levels safely. Children involved will undergo regular assessments including blood tests to monitor kidney function and antibiotic levels, clinical evaluations of fever duration, and tracking of any side effects related to antibiotics. Monitoring will continue throughout antibiotic treatment and up to two weeks after. The main outcome is the early achievement of target antibiotic levels, with secondary measures including fever duration, side effects, and the accuracy of different kidney function formulas. Participation involves close clinical and laboratory follow-up during febrile neutropenia episodes, with treatment adjustments guided by blood results.