Lincoln

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating the effectiveness and safety of pirtobrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study focuses on two parts: Part 1 tests three different doses of pirtobrutinib in participants who have had 1 to 3 prior treatments, including a covalent Bruton tyrosine kinase (BTK) inhibitor. Part 2 evaluates pirtobrutinib alone in participants who have not received prior treatment but have a specific genetic deletion called 17p. This is a phase 2, open-label, randomized study. Pirtobrutinib is given orally to participants in both study parts. Participants in Part 1 receive one of three dose levels, while those in Part 2 receive pirtobrutinib monotherapy. Part 1 participation lasts about 3 years, and Part 2 participation can last up to 2 years. The study compares the effects of different doses and treatment histories to better understand pirtobrutinib’s impact on CLL/SLL. Throughout the study, researchers monitor participants' overall response to treatment from the start up to 3 years. They assess safety and side effects, and participants are required to be able to swallow oral medication and have a performance status that allows them to participate. The study includes regular evaluations to determine how well the treatment controls the disease and to track any adverse events over the course of the study periods.

Researchers are evaluating the safety and effectiveness of bomedemstat (MK-3543) compared with the best available therapy (BAT) in adults with essential thrombocythemia (ET) who have not responded well to or cannot tolerate hydroxyurea. This phase 3 clinical trial aims to determine if bomedemstat provides a better durable clinicohematologic response in these participants. Participants will receive either bomedemstat as an oral capsule or one of the best available therapies, including anagrelide (oral capsule), busulfan (oral tablet), interferon alfa or its pegylated forms (subcutaneous solution), or ruxolitinib (oral tablet). The study involves a randomized, open-label design where treatments are compared directly. Throughout the study, participants will be monitored for their hematologic response up to about 52 weeks. Assessments include platelet and neutrophil counts before starting treatment to ensure eligibility. Safety and efficacy are tracked to evaluate the long-term impact of the treatments on ET.

Researchers are evaluating momelotinib to determine its safety and effectiveness in people with low-risk myelodysplastic syndromes (LR-MDS), a condition affecting blood cell production. This phase 2 study aims to find the best dose of momelotinib that may help reduce the need for red blood cell transfusions. The study also examines how the body processes momelotinib and its major metabolite. The study has two parts. In Part 1, participants receive varying doses of momelotinib to identify the optimal dose based on improvements in red blood cell transfusion needs and safety. In Part 2, participants receive the selected dose from Part 1 to further assess its effects on reducing transfusion dependence and to monitor safety. Momelotinib is given as a drug, and dosing and safety are closely tracked over the study period. Participants will be monitored for red blood cell transfusion independence lasting at least 12 weeks, safety events including severe side effects, and momelotinib blood levels. These assessments occur up to 24 weeks for transfusion outcomes and up to approximately 104 weeks for safety monitoring. The study also measures drug concentration and exposure in the blood to understand how momelotinib is processed. Overall, participant involvement includes treatment, regular safety evaluations, and blood tests to track outcomes and side effects over time.

Researchers are investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral Nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary myelofibrosis. This Phase 1/2 open-label, multicenter, dose-escalation trial includes patients who have previously been treated with JAK inhibitors or are ineligible for them. The study aims to assess how the drug behaves in the body and its safety profile in this patient group. The study consists of three arms: one enrolling patients treated with JAK inhibitors who are intolerant or resistant; a second arm including patients on a stable dose of ruxolitinib but with suboptimal or lost response; and a third arm with patients previously treated with a JAK inhibitor other than momelotinib. Participants receive oral Nuvisertib alone or in combination with ruxolitinib or momelotinib. Treatment dosing and schedules follow a dose-escalation and expansion design specific to each arm. Participants undergo assessments to monitor dose-limiting toxicities within 28 days and treatment-emergent adverse events throughout the study. Researchers also evaluate preliminary activity by measuring spleen volume reduction. Regular laboratory tests, imaging scans, and symptom questionnaires are used to track safety and effectiveness. The total study duration includes screening, treatment, and follow-up periods to ensure comprehensive monitoring of patient outcomes.

Researchers are evaluating the effectiveness of glofitamab given alone compared to an investigator's choice of treatment in patients with relapsed or refractory mantle cell lymphoma (MCL). This Phase III, open-label study focuses on patients whose disease has progressed after previous therapies, including BTK inhibitors. The goal is to see which treatment better controls the lymphoma and prolongs the time before the disease worsens or leads to death. Participants are assigned to receive either glofitamab alone or one of two combination therapies selected by the investigator: rituximab plus bendamustine or lenalidomide with rituximab. All patients receive two pretreatments of intravenous obinutuzumab starting on Cycle 1 Day 1. Those in the glofitamab group begin intravenous glofitamab on Cycle 1 Day 8 and continue for 12 cycles, each lasting 21 days. Patients receiving the combination therapies get intravenous rituximab every 28 days, with bendamustine given on Days 1 and 2 of each 28-day cycle for six cycles, or oral lenalidomide daily on Days 1-21 of each 28-day cycle until disease progression. Tocilizumab is available as needed to manage any cytokine release syndrome events. Throughout the study, participants undergo regular assessments to track disease progression, including imaging and laboratory tests. The primary measure is progression-free survival, defined as the time from randomization until disease worsening or death, monitored for up to about 24 months. Safety is closely observed, and patients are evaluated for treatment response and adverse effects. The study involves ongoing monitoring during treatment cycles and follow-up periods to understand the impact of the therapies on the lymphoma and patient health.

Researchers are evaluating the safety and effectiveness of advanced external beam radiotherapy called stereotactic body radiotherapy (SBRT) in men with high risk localized prostate cancer. This cancer is limited to the prostate but has a high chance of growing quickly or spreading. The study compares SBRT given to the prostate alone versus SBRT given to both the prostate and surrounding lymph nodes. It is a Phase III trial involving 1128 participants to see which treatment option is better and safer over at least three and a half years of follow-up. Participants receive radiotherapy in 5 visits over two weeks. Half of the men will have SBRT targeted only to the prostate, while the other half will have it directed to both the prostate and pelvic lymph nodes. The treatments are delivered at NHS radiotherapy centers experienced with SBRT and pelvic node radiotherapy. Quality assurance ensures the treatments are administered properly. During the study, men will undergo scans including multi-parametric MRI and various types of PET-CT or MRI to stage their cancer before treatment. Researchers will monitor side effects and cancer outcomes to assess safety and effectiveness. The main outcome measured is the time until biochemical or clinical failure, with a minimum follow-up of 3.5 years after randomization. Participants will be closely followed for side effects and cancer control throughout the study period.

Researchers are evaluating the safety and effectiveness of tralokinumab combined with topical corticosteroids (TCS) for treating moderate-to-severe atopic dermatitis (AD) in children and infants. The trial includes two age groups: children aged 2 to under 12 years and infants aged 6 months to under 2 years. The study will last up to 4 years with visits every 2 weeks during the first year and every 6 weeks afterward, some conducted by phone. The goal is to assess improvements in AD severity, symptom relief, general health, and quality of life. Children will be randomly assigned to receive either tralokinumab plus TCS or placebo plus TCS for the first 16 weeks in a double-blind setup, with a 2 in 3 chance of getting tralokinumab. After 16 weeks, all participants will receive tralokinumab plus TCS. Infants will receive open-label treatment with tralokinumab plus TCS throughout the treatment period. The medication is given as subcutaneous injections with dosing based on body weight and adjusted at specified weeks throughout the study. After treatment ends, all participants will have a 4-week safety follow-up. Participants will undergo screening lasting up to 4 weeks to confirm eligibility. During the trial, researchers will monitor skin condition using assessments like the Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) at week 16. Other evaluations include symptom scores and body surface area affected by AD. Safety and health will be closely tracked throughout the study duration.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.