Milwaukee

Researchers are investigating the targets of disease-reactive T cells in patients with various autoimmune diseases, including inflammatory bowel diseases, celiac disease, ankylosing spondylitis, multiple sclerosis, scleroderma, systemic sclerosis with lung involvement, and others. The study focuses on identifying the natural peptide targets recognized by T cell receptors (TCRs) in inflamed tissues, which may help develop new treatments that specifically target these immune responses. This approach uses high-throughput technology developed by TScan to discover these targets from active disease tissues. Participants will provide tissue samples during clinically indicated procedures or research biopsies, along with companion blood samples collected around the same time. The study involves isolating T cells from diseased tissues and matched blood or normal tissues, then identifying T cell clones expanded in the affected organs. These clones' TCR targets will be determined using TScan's genome-wide technology. No specific drug treatments are administered by the study; instead, it collects biospecimens for analysis. During the study, researchers will collect and analyze tissue and blood samples to identify disease-associated TCRs and their peptide targets over a 3-year period. Participants must be willing and able to consent and undergo the procedures. The study tracks T cell targets as the primary outcome, aiming to discover new therapeutic targets. Safety considerations include excluding those with conditions that increase biopsy risks. Total participation duration depends on the timing of tissue collection and subsequent analyses.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

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 a culturally-tailored, home-based physical activity program designed to improve physical fitness in Hispanic or Latino/Latina adolescent and young adult childhood cancer survivors. These survivors may face long-term effects such as weight gain, fatigue, and reduced fitness after cancer treatment, with Hispanic or Latino/Latina individuals potentially at higher risk. The study aims to increase moderate to vigorous physical activity (MVPA) through a mobile health and social media intervention. The study has two stages. Stage 1 involves developing the intervention using feedback from 20 Latinx survivors who speak either English or Spanish. Stage 2 is a randomized controlled trial comparing the intervention group with a control group that only uses a Fitbit tracker. The intervention group receives Fitbit trackers, weekly reminders, goal-setting sessions, social media peer support 2-3 times a week, badges, monthly Zoom meetings, and may choose a physical activity partner who also receives support. After 12 weeks, a 4-week maintenance phase continues these supports with less structure. The control group wears a Fitbit daily for 12 weeks without additional support. Participants wear Fitbit trackers daily, attend weekly sessions, post on social media, and complete interviews and questionnaires. Researchers measure changes in physical activity levels, sedentary time, quality of life, and cardiometabolic health indicators. Data is collected using Fitbit devices, interviews, and surveys, with follow-up over 12 weeks plus maintenance. Safety and acceptability of the intervention are also assessed throughout the study.

Researchers are conducting a first-in-human phase 1 study to evaluate MEN2312, a lysine acetyltransferase 6 (KAT6) inhibitor, in adults with advanced breast cancer. This study focuses on participants whose cancer has recurred locally or metastasized and who have limited treatment options after prior therapies. The trial aims to assess the safety and appropriate dosing of MEN2312, alone or combined with elacestrant, an oral drug also being studied. Participants will receive MEN2312 tablets orally, either as a single treatment or alongside elacestrant tablets. The study allows participants who have undergone up to six prior systemic therapies for advanced disease, including chemotherapy or antibody drug conjugates. The study involves careful selection of participants based on genetic alterations in their tumor tissue related to PIK3CA, AKT1, or PTEN genes. Throughout the trial, researchers will monitor participants for dose-limiting toxicity over the first 28 days and determine the recommended phase 2 dose by six months. Safety assessments, treatment response, and side effects will be tracked closely. Participation requires ongoing evaluations to measure how the participant's cancer responds and to ensure safety while receiving the study treatments.

Researchers are studying BAY 3713372, a new drug being developed to treat solid tumors with a specific genetic change called MTAP deletion. The drug works by blocking a protein called PRMT5, which may kill cancer cells with this deletion while sparing normal cells. This first-in-human study aims to understand the safety, how the body processes the drug, and its effectiveness in people with these MTAP-deleted solid tumors. Participants will receive BAY 3713372 orally every day. The study starts with a dose escalation phase, where different groups get increasing doses to find a safe and effective dose. After this, a dose expansion phase will include more participants receiving the drug alone or with other treatments. Participants can continue treatment as long as they benefit and do not experience severe problems. During the study, participants will visit the study site multiple times before and during treatment, and follow-up visits after treatment ends. Doctors will monitor health through blood and urine tests, heart checks with electrocardiograms, and imaging scans like CT or MRI to track cancer changes. Tumor samples may also be taken. Safety and treatment response will be closely assessed, including adverse events and how the drug behaves in the body. Participants will be contacted every three months for up to two years after treatment to check their health.

Primary immune thrombocytopenia (ITP) is a condition in which the immune system mistakenly destroys platelets, the cells that help stop bleeding. This leads to a low platelet count, making it easier to bruise or bleed. The trial investigates the long-term safety, tolerability, and effectiveness of mezagitamab in adults with chronic primary ITP who have previously participated in certain mezagitamab studies. It also examines how the body processes mezagitamab over time. Participants who completed the previous mezagitamab studies TAK-079-3002 or TAK-079-1004 and meet specific criteria will receive mezagitamab as a subcutaneous injection during this continuation study. The study is open-label and multicenter, focusing on continued treatment based on protocol requirements. The medication is given under medical supervision, and participants return to the study clinic several times throughout the study. During their participation, individuals will undergo regular assessments including monitoring for treatment-emergent adverse events and serious adverse events up to approximately 108 weeks. Researchers will track safety by noting any adverse events that lead to permanent withdrawal from mezagitamab. The study includes physical evaluations, laboratory tests, and ongoing safety monitoring to understand how well participants tolerate the treatment and how effective it is over the long term.

This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date of enrollment in Study 165-501 (incident-users) or who have previously started treatment with pegvaliase at the date of enrollment in Study 165-501 (prevalent-users) are eligible for participation in Study 165-503. Subjects participating in the 165-501 study who consent to participate in this study (165-503) will be requested to provide pre-dose blood samples for Phe, immunologic and inflammatory marker testing approximately every 3 months for the first 3 years of participation, then every 6 months for the remainder of the study. Subjects will be requested to provide additional pre-dose blood samples at the time of Study 165-501 -protocol defined safety events. Additional pre-dose samples will be drawn as per standard of care as detailed in protocol 165-501. The blood Phe, immunologic (PAL IgG, PEG IgG, PEG IgM, anti-pegvaliase IgE), and inflammatory (C3/C4, hsCRP) markers, will be sent to a central laboratory for processing. Data collected in the 165-501 study will be combined with the data collected in this study to decrease burden on sites for data entry and to avoid duplication of ADR reporting (see Criteria for Evaluation). The combined data will be reported in the Clinical Study Report for this study. Subjects can withdraw from Study 165-503 and remain on Study 165-501, but they cannot withdraw from Study 165-501 and remain on Study 165-503 as safety events and other data-points are collected in Study 165-501.

This research follows patients with hemoglobinopathy, including sickle cell disease, who previously received BEAM-101 treatment as part of an earlier study called BTX-AUT-001. The goal is to monitor these patients long-term to assess safety and survival over many years after treatment. The study focuses on understanding the long-term effects of BEAM-101, a gene-edited autologous hematopoietic stem cell therapy. Participants in this follow-up study have all received a single intravenous dose of BEAM-101 after conditioning with busulfan. After completing the parent study, patients are invited to join this long-term study which lasts up to 13 years, extending total follow-up to 15 years since their original BEAM-101 treatment. During this time, patients will have regular safety and efficacy check-ups according to a detailed schedule. Patient visits occur annually for the first five years, then every three years up to year 11, with a final visit at year 15. In addition, virtual or phone check-ins take place every six months through year 5 and then once a year thereafter. Researchers will monitor safety continuously and track mortality throughout the entire follow-up period to gather important long-term data on BEAM-101 treatment.

Researchers are conducting a long-term follow-up study for people previously treated with ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy targeting B-cell maturation antigen (BCMA) used in multiple myeloma. The study aims to collect data on delayed side effects and better understand the long-term safety of cilta-cel over a period of up to 15 years after the last dose. Participants in this study will not receive any new treatments. Instead, the study will track their health in two phases: from year 1 to year 5 after their last cilta-cel dose, then from year 6 up to year 15. Safety evaluations will include monitoring for new or worsening malignancies, neurological, rheumatologic, autoimmune, hematologic disorders, infections, and any serious adverse events. Participants will be followed at least once a year during the study. Assessments will include reviewing adverse events, lab test results, physical exams including neurological checks, and other safety data. This comprehensive monitoring will help researchers understand long-term effects and ensure ongoing participant safety throughout the 15-year follow-up.