Bangor

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are investigating the best way to combine chemotherapy and radiation therapy for patients aged 3 to 29 years with localized non-germinomatous germ cell tumors NGGCT in the brain. This phase II trial aims to optimize treatment based on how well the tumor responds to initial chemotherapy, with the goal of reducing spinal cord relapses and adjusting therapy for better disease control. The study also compares different radiation types and examines cognitive and physical effects in children and young adults with NGGCT. Participants first receive induction chemotherapy consisting of carboplatin, etoposide, and ifosfamide over six cycles every 21 days. Based on tumor response, patients are assigned to one of two plans Plan A involves whole ventricular plus spinal canal irradiation WVSCI, delivered daily for 6 weeks, while Plan B includes high-dose chemotherapy with stem cell transplant followed by radiation therapy to the whole brain and spine. Some patients may undergo second-look surgery depending on tumor response before continuing treatment. Throughout the study, participants undergo MRI scans, collection of cerebrospinal fluid and blood samples, and questionnaires assessing cognitive, social, and behavioral functioning. Researchers monitor tumor response, progression-free survival, overall survival, and patterns of disease recurrence for up to 10 years. Safety and side effects are also evaluated to better understand long-term outcomes of these treatment approaches.

Researchers are evaluating how well combination chemotherapy works in treating patients with newly diagnosed stages 2 to 4 diffuse anaplastic Wilms tumor DAWT and patients with relapsed favorable histology Wilms tumor FHWT. This phase II trial compares the effects of two chemotherapy regimens, UH-3 and ICECycloTopo, on event-free survival and overall survival, aiming to improve outcomes based on different relapse risk groups and prior treatments. The study also explores kidney toxicity, genetic markers, surgery impacts, and radiation therapy techniques to reduce side effects and better understand tumor behavior. Participants are assigned to one of two treatment groups. In Arm I Regimen UH-3, patients receive cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan intravenously over various days in a 21-day cycle, with radiation therapy at week 7 of cycle 3 if needed. In Arm II Regimen ICECycloTopo, patients receive cycles of carboplatin, etoposide, ifosfamide, cyclophosphamide, and topotecan intravenously over 10 cycles every 21 days, with surgery andor radiation therapy during certain cycles as clinically indicated. Throughout the trial, patients undergo multiple imaging tests including CT scans, PET scans, chest x-rays, MRIs, abdominal ultrasounds, and bone scans, along with blood sample collections and biopsies. After completing treatment, follow-up visits occur every 3 months for the first 2 years, then every 6 months for years 3 and 4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years from study entry, with ongoing monitoring for treatment effects and safety.

Researchers are studying children and young adults with newly diagnosed diffuse intrinsic pontine glioma DIPG or high-grade glioma HGG that have a specific genetic change called H3 K27M mutation. This phase III trial evaluates the safety, side effects, and best dose of the drug selinexor combined with standard radiation therapy, and aims to determine how well this combination shrinks tumors in these patients. DIPG is a high-risk brain tumor located in a critical area of the brainstem, and HGG refers to rapidly growing glioma tumors in the brain or spine. Participants receive standard radiation therapy five days a week for 5 to 7 weeks. Beginning on day 4 or 5 of radiation, selinexor is given orally on specific days during this period. After a two-week rest, patients enter a maintenance phase where selinexor is taken orally on days 1, 8, 15, and 22 of each 28-day cycle, for up to 24 cycles if there is no disease progression or unacceptable side effects. Magnetic resonance imaging MRI scans and possibly a biopsy are done before treatment and during follow-up. During the study, participants are monitored closely with MRIs and clinical evaluations to assess side effects and tumor response. Researchers measure the maximum tolerated dose of selinexor, event-free survival, overall survival, and response rates over up to five years. After treatment, patients are followed every three months during the first year, then every six months for two years, and annually for years four and five to track long-term outcomes and safety.

Researchers are comparing two treatments for children and young adults aged 2 to 21 with newly diagnosed or untreated low-grade glioma LGG that does not have a BRAFV600E mutation or neurofibromatosis type 1 NF1. The study aims to find out if selumetinib, a drug that blocks enzymes needed for tumor cell growth, works as well as the standard chemotherapy treatment with carboplatin and vincristine CV. It also evaluates which treatment better improves quality of life and patient outcomes. Participants are randomly assigned to one of two groups. One group receives vincristine intravenously on specific days along with carboplatin intravenously on scheduled days, followed by maintenance cycles every 42 days for up to 8 cycles. The other group takes selumetinib orally twice daily in 28-day cycles for up to 27 cycles. Throughout the trial, patients undergo blood collection, MRI scans, and in the selumetinib group, echocardiography at baseline. Treatments continue unless there is disease progression or unacceptable side effects. During participation, patients have various assessments including tumor imaging, blood tests, and evaluations of vision and motor function. Quality of life and cognitive, social, emotional, and behavioral functions are also measured. After treatment, patients are followed every 3 months for the first year, every 6 months for years 2 and 3, and then annually up to 10 years. The main outcome measured is event-free survival over this period.

Researchers are evaluating the combination of nivolumab and blinatumomab compared to blinatumomab alone in children and young adults aged 1 to under 31 years with first relapse of CD19 B-cell acute lymphoblastic leukemia B-ALL, including patients with Down syndrome. This phase II trial aims to compare event-free survival after reinduction and consolidation therapy, assess safety and tolerability, and explore various outcomes such as remission rates and toxicity, with follow-up up to 10 years after enrollment. Participants receive treatments based on their assigned groups and arms, involving cycles of immunotherapy including blinatumomab, nivolumab, dexamethasone, methotrexate, and other chemotherapy drugs given by various routes such as intravenous infusion, intrathecal injection, and oral administration. Treatment cycles repeat every 36 or 37 days for up to two cycles, with some groups receiving radiation therapy or maintenance chemotherapy afterward. Patients with high white blood cell counts or specific disease locations may receive pre-immunotherapy treatments. Throughout the study, participants undergo lumbar punctures, bone marrow biopsies and aspirations, and collection of blood, urine, and cerebrospinal fluid for monitoring. Researchers measure outcomes such as minimal residual disease negative remission rates and event-free survival. After completing treatment, participants are followed every three months for one year to monitor their health and any long-term treatment effects.

Researchers are evaluating a new treatment approach for children and young adults newly diagnosed with acute myeloid leukemia AML, including those with and without FLT3 gene mutations. The trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with CPX-351, a liposome-encapsulated form of daunorubicin and cytarabine, andor the drug gilteritinib which may block abnormal FLT3 gene function. The study aims to understand which treatment works better and to monitor heart function changes during and after therapy. Participants are assigned to different treatment groups based on their risk and FLT3 mutation status. Treatments include various chemotherapy regimens delivered intravenously and intrathecally, with some groups receiving CPX-351 and others receiving standard drugs. Patients with FLT3 mutations receive additional oral gilteritinib for extended periods, including maintenance therapy up to one year. Hematopoietic stem cell transplantation is also part of the treatment for some high-risk patients following chemotherapy courses. During the study, participants will undergo multiple assessments including blood tests, bone marrow biopsies, imaging scans, and neuropsychological testing to monitor leukemia status and treatment effects. Cardiac function is closely followed using echocardiography and biomarkers. Patient outcomes such as event-free survival, overall survival, minimal residual disease, relapse rates, and treatment safety are tracked for up to three years. The total study participation may extend over several years with ongoing evaluations.

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to the standard treatment of chemotherapy with or without radiation improves survival for patients aged 5 to 60 with early stage classical Hodgkin lymphoma. This phase III trial compares progression-free survival and overall survival between the standard therapy and the immunotherapy-enhanced approach, as well as patient-reported outcomes and long-term side effects. Participants initially receive two cycles of ABVD chemotherapy every 28 days and then undergo imaging to classify their early response. Based on risk level and response, patients are assigned to one of eight treatment arms that include either continuing standard chemotherapy, receiving immunotherapy drugs, or combinations with involved-site radiation therapy. Treatments are delivered intravenously or orally in cycles lasting 28 days. Imaging and blood samples are collected throughout the trial. Participants are monitored regularly with PET scans, CT or MRI imaging, and blood tests. Follow-up visits occur every 3 months in the first year, then every 6 months for years two and three, and annually up to 12 years from registration. Researchers assess survival outcomes, adverse events, patient-reported symptoms and quality of life, and metabolic tumor burden. Long-term effects such as cardiovascular and pulmonary health are also evaluated using questionnaires and clinical assessments.

This research aims to evaluate the long-term safety and explore the efficacy of astegolimab in adults aged 40 to 90 years with chronic obstructive pulmonary disease COPD. It focuses on participants who have completed a 52-week placebo-controlled treatment period in previous studies GB43311 or GB44332. The study is a phase 3, open-label extension to gather extended safety information on this drug in COPD patients. Participants from the parent studies who qualify will receive subcutaneous injections of astegolimab every two weeks throughout the study until it ends. This open-label extension allows all participants to receive the active drug without placebo comparison. The study continues treatment beyond the initial 52-week period to monitor long-term effects. During the study, participants will be monitored for adverse events up to 12 weeks after their last dose of astegolimab. Researchers will collect safety data to understand the incidence of any side effects. The study involves regular assessments and follow-ups to ensure participant well-being, with the total duration lasting until July 2034.

Researchers are studying the safety and immune response of a fifth dose of the Lyme disease vaccine called VLA15 in healthy individuals aged 7 years and older who have already received four doses of this vaccine. This Phase 3 trial compares the effects of the vaccine against a placebo saline to better understand its protection against Lyme disease. The study is randomized, placebo-controlled, and double-blinded, aiming to assess tolerability and immune response. Participants receive one injection, either VLA15 or saline, into the muscle of the upper arm at their first visit. They are randomized in a 51 ratio to either vaccine or placebo. The timing of the fifth dose varies, occurring either one or two years after the fourth dose from a previous study. The trial includes about 1712 participants and uses an independent data monitoring committee to oversee safety. During approximately 12 months of participation, individuals will attend four clinic visits. These visits include health checks, blood draws to measure immune response, and receiving the study injection during the first visit. Researchers will monitor local and systemic reactions within seven days post-injection, adverse events up to one month, and longer-term safety for up to a year. The main outcomes focus on immune responses to different parts of the vaccine and recording any side effects or new medical conditions.