Melrose Park

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 how effective, safe, and tolerable a vaccine for Clostridioides difficile (C. difficile) infection is in adults aged 65 years and older. The study focuses on reducing the number of C. difficile infections, which can cause diarrhea, in this older adult population. This is a Phase 3, placebo-controlled, double-blinded, randomized trial involving participants who are at risk because of recent or planned contact with healthcare systems or recent antibiotic use. Participants will receive either the C. difficile vaccine or a saline placebo. Both are given by injection into the upper arm muscle. The study includes 3 planned clinic visits and 3 phone visits initially, followed by yearly clinic visits until the study ends. Participants will remain in the study until enough infection events have occurred—this period may last up to about three and a half years, but could be shorter or longer depending on how quickly events happen or if the study stops early due to clear results. Throughout the study, participants will report any side effects such as local reactions and systemic events for 7 days after each vaccination, and adverse events for up to one month. Serious adverse events are monitored for up to 18 months after the last dose. If participants experience 3 or more loose stools within 24 hours during the study, they must save the next stool and contact the study team for infection testing. This ongoing monitoring helps assess the vaccine's impact on preventing medically attended C. difficile infections over time.

This research collects data and biological samples from patients who have experienced side effects from immunotherapy treatments for cancer. The goal is to create a national collection of these samples and clinical information to help future studies understand, predict, prevent, and treat serious immune-related side effects, rare infections, or rapid tumor growth after immunotherapy. Participants provide tissue and blood samples when they join the study and again one month later. Some patients may also provide stool samples if they have certain side effects like colitis. Researchers also review participants' medical records for up to one year to gather detailed health information related to their treatment and side effects. During the study, patients undergo sample collections and have their health records examined. The main outcome measured is the establishment of a national biorepository containing these samples and data, which will be used in future research over the course of one year. This study aims to support better understanding and management of immunotherapy side effects in cancer treatment.

Researchers are evaluating three different combinations of drugs to treat newly diagnosed multiple myeloma in patients who are considered frail or intermediate-fit and are not eligible for stem cell transplant. This phase III trial focuses on comparing these three-drug induction treatments followed by either double- or single-drug maintenance therapy. The study aims to determine which treatment combination better controls the disease and improves progression-free survival and overall survival. Patients are randomly assigned to one of three treatment groups. Arm 1 (VRd-Lite) receives bortezomib by injection under the skin, lenalidomide by mouth, and dexamethasone by mouth during induction cycles, followed by lenalidomide alone for maintenance. Arm 2 (DRd-R) receives daratumumab and hyaluronidase-fihj injections, lenalidomide, and dexamethasone during induction, followed by lenalidomide alone during maintenance. Arm 3 (DRd-DR) receives the same induction as Arm 2, but maintenance includes both daratumumab and lenalidomide. Induction cycles last up to 9 cycles of 28 days each, and maintenance cycles continue every 28 days if the disease does not progress or toxicity occurs. Participants undergo assessments including tumor evaluations, whole-body imaging, blood tests, and quality-of-life questionnaires. After completing treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years. Researchers will measure progression-free survival, overall survival, response rates, safety, minimal residual disease, and patient-reported health outcomes to understand the treatments' effects and support future care decisions.

Researchers are evaluating treatments for patients with metastatic kidney cancer to see if adding surgery to standard immunotherapy-based drug combinations improves outcomes. This phase III trial focuses on kidney cancer that has spread to other parts of the body. The study compares standard immunotherapy drugs, which help the immune system fight cancer, with or without the surgical removal of the kidney, known as nephrectomy. Doctors currently do not agree on whether surgery adds benefit when combined with these immunotherapy treatments. Participants first receive one of three immunotherapy-based drug regimens, including combinations of nivolumab, ipilimumab, pembrolizumab, avelumab, and axitinib, given through intravenous infusions and oral tablets over several weeks. After 10-14 weeks of this initial treatment, patients are randomly assigned to either continue immunotherapy drugs alone or to also have kidney surgery followed by the same drugs. Surgery may be done by different methods and must occur within 8 weeks of randomization. Axitinib is stopped at least 24 hours before surgery. During the study, participants undergo regular scans of the chest, abdomen, and pelvis to assess disease status. They are monitored for survival for up to 7 years after randomization, with follow-up visits every 3 months in the first year, then every 6 months for two years, and annually thereafter. Researchers also evaluate tumor response, surgical complications, and drug side effects. Specimens are collected for future research, and participants' health and treatment effects are closely followed throughout the study period.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating how well inotuzumab ozogamicin and blinatumomab, with or without ponatinib, work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia (ALL). This includes patients with newly diagnosed, recurrent, or treatment-resistant (refractory) forms of the disease, both Philadelphia chromosome-negative and positive. This phase II trial aims to confirm tolerability, estimate survival rates, response rates, and assess safety and molecular responses in different patient cohorts. Participants are assigned to one of three cohorts based on their disease status and Philadelphia chromosome status. Treatments include intravenous inotuzumab ozogamicin and blinatumomab given in cycles over several weeks, with some groups also receiving daily oral ponatinib. Various courses of treatment are outlined, including induction, consolidation, maintenance, and extended therapy depending on response. Procedures such as bone marrow biopsies, lumbar punctures with cerebrospinal fluid collection, and blood draws are performed throughout the study. During the study, patients undergo regular assessments including bone marrow aspiration, blood tests, and lumbar punctures to monitor disease status and treatment effects. Researchers measure event-free survival, treatment completion, response rates, molecular responses, and safety outcomes over periods up to 10 years. Follow-up visits occur every three months for three years and then every six months up to ten years to monitor long-term outcomes and safety.

Researchers are evaluating how well inotuzumab ozogamicin works when combined with frontline chemotherapy in treating young adults aged 18 to 39 years who have newly diagnosed B acute lymphoblastic leukemia (ALL). This Phase III trial aims to confirm the safety and effectiveness of adding inotuzumab ozogamicin, a monoclonal antibody that targets cancer cells, to a pediatric-inspired chemotherapy regimen called CALGB 10403. The study also explores the impact of this combination on survival, minimal residual disease, genetic factors, treatment side effects, and medication adherence. Participants begin with remission induction therapy that includes oral allopurinol, intravenous and intrathecal chemotherapy drugs such as daunorubicin, vincristine, dexamethasone, pegylated L-asparaginase, and methotrexate, along with bone marrow tests. Those who respond to induction are randomized to one of two groups: one receives standard chemotherapy courses including consolidation, maintenance, and intensification phases, while the other receives inotuzumab ozogamicin infusions in addition to the same chemotherapy regimen. Treatments are given by mouth, intravenous, subcutaneous, or intrathecal routes on specific days over several courses lasting up to three years for maintenance therapy. Throughout the study, participants undergo regular bone marrow biopsies, blood tests, and biomarker analyses to monitor disease status and treatment effects. Researchers assess event-free survival, disease-free survival, overall survival, treatment toxicity, genetic markers, and medication adherence using electronic monitoring. After treatment ends, patients are followed monthly for the first year, then less frequently up to ten years to track long-term outcomes and safety.

Researchers are investigating treatments for patients with high-risk smoldering multiple myeloma in this phase III trial. The study compares the effects of lenalidomide and dexamethasone given with or without daratumumab. These drugs work in different ways to stop tumor growth, and the combination with daratumumab, an immunotherapy, may better interfere with tumor cell growth and spread. The trial aims to assess overall survival, progression-free survival, treatment safety, and quality of life among participants. Participants are randomly assigned to one of two treatment groups. One group receives daratumumab intravenously on specific days across up to 24 cycles, combined with daily oral lenalidomide for 21 days and oral dexamethasone on days 1, 8, 15, and 22 for 12 cycles. The other group receives only lenalidomide and dexamethasone on the same schedule for up to 24 cycles. Treatment continues every 28 days until disease progression or unacceptable side effects occur. During the study, participants undergo regular assessments including blood tests, bone marrow biopsies, imaging scans, and patient questionnaires to monitor treatment effects and quality of life. Researchers track overall survival for up to 15 years, evaluate minimal residual disease, and monitor medication adherence and adverse events. Follow-up visits occur every 3, 6, or 12 months after treatment ends to continue monitoring health outcomes.

Researchers are evaluating a screening and multi-sub-study randomized phase II/III trial called Lung-MAP, designed for patients with previously treated non-small cell lung cancer. The trial aims to establish a genomic screening method to assign patients to biomarker-driven or non-matched sub-studies. Depending on the cancer biomarker type, participants may receive new targeted cancer therapies or combinations compared to standard care, with the goal of approving new treatments. An optional ancillary study explores patient and physician attitudes about returning genetic findings related to germline mutations. The study involves testing patient specimens to determine eligibility for various sub-studies under the Lung-MAP protocol. Patients undergo screening to analyze tumor tissue and blood samples for biomarkers including PD-L1 and c-MET. Those requiring a fresh biopsy also submit blood for circulating tumor DNA testing. Sub-study assignment depends on the molecular profile results. This screening process includes both patients progressing after prior therapy and those pre-screened before progression on current treatment. Participants provide informed consent and tumor tissue that meets quality standards for testing. Researchers collect clinical data including smoking history and performance status. Outcomes focus on screening success, such as adequate tissue submission and matching to biomarker-driven sub-studies, tracked for up to three years. The study also monitors patient and physician knowledge and preferences regarding genomic findings. Participation duration varies based on screening and sub-study assignment.