Medical College Wisconsin

This research aims to better understand treatment outcomes for patients with advanced pancreatic ductal adenocarcinoma PDAC whose tumors have a specific KRAS G12R mutation. It focuses on evaluating the safety and effectiveness of different therapies involving mitogen-activated protein kinase kinase inhibitors MEKi combined with other treatments. The study also assesses whether it is feasible to conduct future clinical trials using these combination therapies. The study observes patients receiving one of several treatment approaches therapy without MEKi, therapy combining MEKi with hydroxychloroquine HCQ, therapy combining MEKi with an epidermal growth factor receptor inhibitor EGFRi, or other MEKi-based combination therapies. Patients tumor mutations are confirmed through molecular testing such as next-generation sequencing or circulating tumor DNA panels chosen by their doctors. Treatments are administered as part of the patients standard care, and data is collected both retrospectively and prospectively. Participants provide medical records and undergo molecular profiling to track tumor response, survival rates, and any treatment-related side effects. Researchers analyze these outcomes over time, including the number of patients without disease progression at six months and responses or adverse events over two years. The study continues until 2027 and involves reviewing patient outcomes to guide future therapy strategies and clinical trial planning for this patient group.

Researchers are conducting an observational study at the Medical College of Wisconsin Cancer Center to collect and analyze data from patients receiving cancer-related treatments. This master protocol supports both retrospective and prospective data collection, including biospecimen sampling, to advance research on individualized cancer therapy. The study uses advanced technologies like machine learning and artificial intelligence to analyze patient data and biological samples for better understanding of cancer treatment responses. This study is non-therapeutic and involves gathering patient data from past and current medical records, as well as collecting new samples of blood, stool, or urine when relevant. These specimens may be analyzed using various scientific techniques to discover biomarkers and investigate molecular and treatment-related features. Participation involves consenting to data and specimen collection during routine cancer care. Participants will provide data that researchers will analyze to observe the number of patients receiving precision cancer therapies and those who do not, alongside their biospecimen contributions over one year. The study aims to minimize burden by combining multiple low-risk research projects under one protocol. Participants can expect routine medical care alongside observational assessments, with no study treatments administered as part of this research.

Researchers are studying real-world patient characteristics, treatment patterns, and both short- and long-term outcomes in people with symptomatic obstructive hypertrophic cardiomyopathy HCM across the United States and Europe. The study focuses on patients receiving mavacamten, other treatments for obstructive HCM, or no treatment due to intolerance or prior treatment failure. The U.S. portion evaluates the safety of mavacamten in this setting, while the European part assesses both its effectiveness and safety. Participants receive treatments as part of standard care, either mavacamten or other medications such as beta-blockers, non-dihydropyridine calcium channel blockers, or disopyramide. Treatments are prescribed by physicians according to routine clinical management. The study observes outcomes over time without altering prescribed care. During the study, participants are monitored for changes in heart function, symptoms, and adverse events through clinical assessments including echocardiography and patient-reported questionnaires. Researchers evaluate heart failure events, heart function measures like left ventricular outflow tract gradient and ejection fraction, arrhythmias, hospitalizations, mortality, and quality of life scores. Data is collected at baseline and followed for up to five years to understand real-world treatment effects and safety.

Researchers are investigating biomarkers related to upper arm motor recovery in people who have recently had an ischemic stroke, with the goal of improving future recovery treatments. This observational study aims to validate key biomarkers measured by transcranial magnetic stimulation TMS and MRI within days of stroke onset. It will also explore these biomarkers in cases of acute intracerebral hemorrhage, creating a large, multicenter dataset combining clinical, TMS, and MRI data. Participants include up to 657 stroke patients who undergo assessments during the acute stroke period. The study uses FDA-cleared TMS devices to measure motor evoked potentials MEP within the first week of hospitalization. MRI scans measure injury to motor pathways. The study validates the Predict Recovery Potential PREP-2 tool, which uses clinical and biomarker data to predict upper extremity outcomes at 90 days. Participants are assessed for motor impairment, function, and use of the affected arm. During the study, participants undergo evaluations including TMS and MRI within the first days after stroke, followed by clinical assessments of upper limb motor outcomes 90 days later. The main outcomes measured are the Upper Extremity-Fugl Meyer score and the Action Research Arm Test at 90 days post-stroke. Participants must be available for in-person visits and comply with all study procedures. The study collects comprehensive data to help improve prediction and treatment of arm recovery after stroke.

Researchers are evaluating the safety and effectiveness of CAR-2019-T cells expanded with Interleukin-7 and Interleukin-15 IL-7IL-15 in adults with relapsed or refractory B cell malignancies, including various types of non-Hodgkin lymphoma, chronic lymphocytic leukemia CLL, and central nervous system CNS lymphoma. This Phase 12 study also examines how flexible manufacturing of these CAR-T cells affects treatment feasibility and outcomes. The trial includes several groups to test different manufacturing processes and patient populations. Participants receive a fixed dose of 2.5 million CAR-2019-T cells per kilogram of body weight, expanded with IL-7IL-15. The study has multiple arms, including flexible manufacturing with 8- or 12-day production times, a fixed 12-day manufacturing process, and a group with cryopreserved CAR-T cells before infusion. Separate groups also focus on CLL and CNS lymphoma patients. The Phase 2 portion measures the complete response rate at three months in mantle cell lymphoma MCL patients. During the study, patients undergo detailed assessments including brain MRI and lumbar puncture when needed, disease measurement through scans or biopsies, and blood tests to monitor safety and treatment effects. Researchers track adverse events within the first 28 days after infusion as a primary outcome. Participants are monitored for safety, treatment response, and long-term follow-up. The total study duration and specific procedures depend on the study arm and patient condition.

Researchers are evaluating the safety and proper dosing of INBRX-106, a hexavalent OX40 agonist antibody, alone or combined with pembrolizumab Keytruda in adults with locally advanced or metastatic solid tumors. This Phase 12, open-label, non-randomized study aims to find the maximum tolerated dose and recommended Phase 2 dose of INBRX-106 while monitoring its effects in various solid tumor types, including non-small cell lung cancer, melanoma, head and neck cancer, renal cell carcinoma, urothelial carcinoma, and others. Participants receive INBRX-106 either alone or in combination with pembrolizumab, with some groups also receiving chemotherapy drugs like carboplatin, pemetrexed, cisplatin, paclitaxel, nab-paclitaxel, or gemcitabine. Treatments are given through intravenous infusions in cycles typically lasting 3 weeks, with some dosing schedules alternating every 6 weeks or involving priming doses. The study includes multiple parts and cohorts focusing on different tumor types, treatment combinations, and disease stages, such as neoadjuvant and adjuvant therapies for resectable non-small cell lung cancer. During the study, participants undergo regular clinical assessments to monitor safety, including tracking adverse events and determining dose tolerance, as well as evaluating antitumor activity. Blood samples are collected for drug levels and immune response measurements over about two years. Participants may have imaging and other tests as needed, and safety monitoring continues throughout treatment. The study lasts until July 2033, with ongoing evaluations of how participants respond and tolerate the treatments administered.

Researchers are evaluating a treatment for mild to moderate COVID-19 using SARS-CoV-2 specific cytotoxic T lymphocytes CTLs derived from family donors who had previously been infected. This pilot study aims to assess the safety and potential effectiveness of these CTLs combined with standard care, as there is currently no FDA-approved therapy for COVID-19. The study involves adults aged 18 to 65 who are hospitalized with confirmed SARS-CoV-2 infection and at higher risk due to certain medical conditions. Participants are randomly assigned to one of two groups one group receives up to five infusions of family donor-derived SARS-CoV-2 CTLs every two weeks alongside standard care, while the other group receives only standard care for COVID-19. The donor must be HLA matched, recovered from COVID-19 at least 10 days prior, and need not have a negative COVID-19 test. The study includes phases 1 and 2 to evaluate safety and response. During the 12-week study period, participants are monitored for adverse events as the primary outcome measure. Safety assessments and clinical evaluations occur regularly to track responses and side effects. The research team collects data on the incidence of adverse events and overall participant health while receiving the infusions and standard care. The study is sponsored by New York Medical College and runs until the end of 2026.

Researchers are studying adult patients with relapsed or refractory B-cell non-Hodgkin lymphoma NHL to evaluate the safety and impact of combining LV20.19 CAR T-cell therapy with pirtobrutinib. This phase I, open-label, single-arm treatment study focuses on patients whose disease has not responded to prior therapies, including various lymphoma subtypes such as follicular, mantle cell, and diffuse large B-cell lymphoma. The study builds on previous findings that identified a safe dose of pirtobrutinib, a novel oral Brutons tyrosine kinase inhibitor, with a favorable toxicity profile. Participants will receive pirtobrutinib orally at 200 mg daily starting at least 14 days before apheresis as a bridging therapy until lymphodepletion begins. After the infusion of LV20.19 CAR T cells, administered intravenously at a dose of 2.5 million cells per kilogram, pirtobrutinib will be restarted between days 28 and 120 as maintenance therapy for up to one year. The CAR T cells may be given fresh or thawed from cryopreservation. This design aims to assess the combination treatments safety and efficacy. Throughout the study, participants will undergo regular monitoring for adverse events related to both CAR T-cell infusion and pirtobrutinib administration at defined periods, including up to 28 days after infusion and during maintenance therapy for up to one year. Assessments include clinical evaluations, laboratory tests, and imaging to document disease status and response. The total study period extends until 2030, allowing long-term follow-up to evaluate treatment effects and safety in this patient population.

Researchers are investigating the use of molecular profile-based evidence to guide personalized cancer treatment for patients with aggressive cancers that have poor prognoses. This study is open-label and non-randomized, including patients with various cancer types to see if matching treatment to molecular changes can be effective across different cancers. The aim is to evaluate the feasibility of this molecular matching strategy for individualized therapy. Patients will be divided into three groups based on disease status and treatment history Group 1 includes patients with localized disease who have not received prior treatment and are eligible for neoadjuvant therapy, have unresectable disease, or are medically unfit for surgery Group 2 includes treatment-nave patients with metastatic disease and Group 3 includes patients with metastatic or unresectable disease who have received at least one prior systemic therapy. Molecular profiling of tumor tissue or blood will guide treatment recommendations by a Molecular Tumor Board. Patients receiving matched therapy form Arm A, while those receiving unmatched therapy or with no molecular alterations form Arm B. Participants will undergo molecular profiling if not already done, and their treatment will be guided accordingly. Researchers will assess feasibility by measuring enrollment success, turnaround times, and actionable molecular findings. The primary outcome is the proportion of patients receiving matched treatment at eight months. Secondary outcomes include the identification of actionable alterations and treatments recommended by the Molecular Tumor Board. Participants will be monitored throughout treatment, with assessments to evaluate treatment response and safety.

Researchers are evaluating the effectiveness of two drugs, zanzalintinib and everolimus, in participants with previously treated, unresectable, locally advanced, or metastatic neuroendocrine tumors. This study includes participants with pancreatic or extra-pancreatic neuroendocrine tumors that have shown disease progression after prior treatments. The trial is a Phase 23, randomized, open-label study aiming to compare these treatments to better understand their impact on this condition. Participants will be randomly assigned to receive either everolimus or zanzalintinib as oral tablets taken once daily. The study follows a sequential model where participants receive one of the two study drugs, and treatment continues as per protocol. There is no placebo group, and the study is designed to monitor and compare the treatments over an extended period. During the study, participants will be regularly assessed through imaging tests like CT or MRI scans to measure tumor progression using RECIST 1.1 criteria. Researchers will monitor progression-free survival, overall survival, response rates, duration of response, and disease control rates up to 48-60 months. Participant-reported quality of life and symptoms will also be evaluated using specific questionnaires. Safety will be monitored by tracking adverse events throughout the study duration.