Cincinnati

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the use of 18F-Fibroblast Activation Protein Inhibitor 18F-FAPI-74 positron emission tomography PET as a noninvasive biomarker to assess lung disease and fibrosis in patients with active tuberculosis TB. The study focuses on microbiologically confirmed TB patients to determine if 18F-FAPI-74 PET can detect fibrosis in TB lesions with high sensitivity. Participants will receive a single intravenous dose of 18F-FAPI-74 followed by a PETCT scan performed either during the first six weeks of TB treatment or within six weeks after completing six months of TB treatment. Some patients may have a second PETCT scan after treatment completion to compare findings. This process allows assessment of fibrosis at different stages of TB treatment. During the study, participants will undergo whole-body PET scans after injection of 18F-FAPI-74, with imaging correlated to sites of TB lesions identified on computed tomography CT. Researchers will measure the uptake of 18F-FAPI-74 using standardized uptake values within one hour. Participants will provide informed consent and comply with scheduled visits and procedures. Safety and laboratory tests will be monitored throughout the study.

Researchers are evaluating the imaging agent 64Cu-LNTH-1363S in patients with sarcomas or gastrointestinal tract GIT cancers to assess its safety, determine the best imaging dose and timing, and compare the imaging results with fibroblast activation protein FAP expression in tumor samples. This Phase 12a open-label study is divided into two parts and aims to better understand how this radiolabeled agent behaves in the body and how well it highlights tumors that express FAP. In Part 1, six patients with metastatic sarcomas will receive a fixed dose of 64Cu-LNTH-1363S to evaluate its distribution, radiation dose, and optimal imaging window during a one-day intervention, followed by a safety follow-up. In Part 2, approximately 20 patients with non-metastatic, operable sarcomas or GIT cancers scheduled for surgery will receive the optimal dose determined in Part 1 to study the correlation between imaging results and tissue FAP expression. Both parts include detailed cardiac monitoring to assess any changes in heart activity related to the agent. Participants will undergo screening before receiving the imaging agent, followed by serial PETCT scans at multiple timepoints on the intervention day to measure biodistribution and image quality. Tissue samples collected during surgery will be analyzed to compare with imaging findings. Safety and tolerability will be monitored through follow-up visits, ECGs, and phone contact. The total study duration varies from about three weeks for Part 1 to up to 11 weeks for Part 2, including surgery and post-surgery sample collection.

Researchers are working to create and use a comprehensive database focused on intracranial aneurysms IA. This project collects and studies clinical history, imaging data, biological samples, and other information to understand factors linked to the formation and rupture of aneurysms. They aim to identify genetic, environmental, and anatomical markers, as well as evaluate outcomes from different treatment strategies and improve patient care protocols. Participants include patients with diagnosed aneurysms, both ruptured and unruptured, family members of affected individuals, and healthy volunteers. Data collected involves detailed clinical records, imaging scans like MRI angiography and CT angiography, and various biological samples such as blood, cerebrospinal fluid, saliva, and stool. Consent covers access to medical records, use of biological samples, and potential future research uses including genetic analyses. During the study, participants provide health and lifestyle information, imaging data, and biological samples. Researchers will monitor multiple long-term outcomes including disease progression, life expectancy, quality of life, neurological and cognitive status, and treatment effects over periods up to 20 years. Data confidentiality is maintained, and participants can withdraw at any time without affecting their medical care. The study aims to validate disease models and support advances in aneurysm management and research.

Researchers are studying new treatment options for people with high-risk non-muscle invasive bladder cancer HR NMIBC, including cases with carcinoma in situ CIS. HR NMIBC affects the lining of the bladder but has not spread to muscle or beyond. The study aims to learn if adding intismeran autogene V940 to the standard Bacillus Calmette-Guerin BCG immunotherapy can improve outcomes by helping the immune system attack the cancer more effectively. Participants are divided into groups receiving different treatments. One group Cohort A receives both intismeran autogene via intramuscular injection every 3 weeks for 9 doses and BCG instillations weekly in specific weeks over about 75 weeks. Another group receives only BCG following the same weekly schedule. A third group Cohort B receives intismeran autogene alone every 3 weeks for 9 doses. The study evaluates these treatments over several years. During the study, participants will have regular treatments and follow-up visits where researchers will monitor cancer progression, recurrence, and survival for up to approximately 5 years. Assessments include event-free survival, recurrence-free survival, overall survival, response rates, time to cystectomy, and safety outcomes such as adverse events and treatment discontinuation. The study is randomized and open-label, with detailed long-term monitoring planned.

Researchers are evaluating letermovir in children and adolescents under 18 years old who weigh less than 40 kilograms and have received a kidney transplant. The study aims to understand how letermovir behaves in the body over time and to assess its safety and how well participants tolerate it. This phase 1, open-label study focuses on cytomegalovirus CMV prevention in this specific pediatric transplant population. Participants who are between 4 and 52 weeks post-kidney transplant will receive letermovir either orally as tablets or pellets, or through a gastrostomy or nasogastric tube as pellets, for 7 consecutive days. The dosing is adjusted based on weight bands. This is a single-group study without a placebo or comparator arm. During the study, participants will be closely monitored through blood samples to measure drug levels and CMV DNA, including the primary outcome of the drug concentration area under the curve over 24 hours on Day 7. Safety will be assessed by recording any adverse events up to 21 days and study discontinuations due to adverse events up to 7 days. The study is expected to last until 2028 and includes assessments of kidney function stability and medication absorption tolerability.

Researchers are investigating new treatment options for breast cancer that is hormone receptor-positive HR and human epidermal growth factor receptor 2-negative HER2-, specifically for cases that are unresectable locally advanced or metastatic. This type of breast cancer involves cancer cells that depend on hormones like estrogen or progesterone and have low HER2 protein levels. The study focuses on comparing the effects of patritumab deruxtecan against chemotherapy or trastuzumab deruxtecan in patients whose cancer has progressed despite prior treatments. Participants receive either patritumab deruxtecan through intravenous infusions every three weeks for about 13 months or a treatment chosen by their physician, which may include various chemotherapy drugs or trastuzumab deruxtecan, administered according to specific schedules for up to 13 months. The study is randomized and open-label, meaning participants are randomly assigned to one of the treatment groups, and both the patients and researchers know which treatment is given. Throughout the study, participants undergo regular assessments to monitor cancer progression and overall survival for up to approximately 85 months. Researchers evaluate tumor response, duration of response, and changes in quality of life using standardized questionnaires. Safety is carefully monitored by recording adverse events and treatment discontinuations. The goal is to understand if patritumab deruxtecan can improve outcomes compared to current treatment options.

Researchers are investigating new treatments for high-risk, early-stage breast cancer, specifically targeting two types triple-negative breast cancer TNBC and hormone receptor-low positiveHER2-negative breast cancer. These cancers are characterized by low or no HER2 protein and low hormone receptor presence. The study aims to evaluate if adding sacituzumab tirumotecan sac-TMT to pembrolizumab and chemotherapy can better reduce cancer cells in tumors and lymph nodes and improve the length of time patients live without cancer progression compared to pembrolizumab with chemotherapy alone. Participants in this trial receive one of two treatment plans. One group gets sacituzumab tirumotecan intravenously every two weeks plus pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab with carboplatin and paclitaxel for another 12 weeks. After 3 to 6 weeks, surgery and optional radiation therapy take place, followed by pembrolizumab for about 28 weeks. Participants with remaining disease may receive additional treatments chosen by their doctors, including olaparib, capecitabine, doxorubicin, epirubicin, or cyclophosphamide. The other group receives chemotherapy drugs carboplatin and paclitaxel with pembrolizumab initially, then pembrolizumab with cyclophosphamide and doxorubicin or epirubicin, followed by surgery, optional radiation, and pembrolizumab for about 28 weeks, with similar additional options for residual disease. During the study, participants undergo core needle biopsies, receive intravenous infusions of study drugs, and have surgery and possible radiation therapy. Researchers assess outcomes such as the percentage of participants with no detectable cancer cells at surgery pathological complete response, event-free survival up to about 92 months, and overall survival up to nearly 10 years. Quality of life and side effects are monitored through questionnaires and adverse event tracking. The study lasts several years, with various assessments throughout treatment and follow-up periods to gather comprehensive data on treatment effects and safety.

Researchers are studying pulmonary arterial hypertension PAH, a condition where lung blood vessels become thick and narrow, causing high blood pressure in the lungs and making it hard for the heart to work. PAH can cause difficulty breathing and limit activity. While standard treatments help symptoms, they do not stop the disease from worsening. This research focuses on sotatercept, a targeted therapy aimed at specific proteins involved in PAH, to learn about its long-term safety and tolerability when added to usual PAH treatments. Participants in this long-term follow-up study, who previously took part in certain sotatercept trials, may continue receiving sotatercept by subcutaneous injection every three weeks. Those coming from blinded studies start at 0.3 mgkg with possible increases up to 0.7 mgkg, while those from unblinded studies continue their current dose with possible titration to 0.7 mgkg. The study monitors participants over an extended period to assess continued effects alongside their usual PAH therapy. During the study, participants will have regular assessments including monitoring for adverse events, blood tests for blood components and chemistry, body weight, blood pressure, and ECG readings. Researchers will also evaluate exercise capacity, heart function markers, and risk scores related to PAH. The study aims to follow participants for up to approximately 7 to 8 years to understand long-term safety, treatment tolerability, and health changes while using sotatercept with standard PAH care.

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. The study compares two treatment combinations to see if more people respond to zilovertamab vedotin MK-2140 plus R-CHP versus polatuzumab vedotin plus R-CHP. This Phase 2 trial aims to assess the effectiveness and safety of these regimens in participants with newly diagnosed GCB DLBCL. Participants receive either zilovertamab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone R-CHP, or polatuzumab vedotin combined with R-CHP. Treatments are given by intravenous infusion on Day 1 of each 3-week cycle for up to 6 cycles, approximately 4 months, with prednisone or prednisolone taken orally for 5 days of each cycle. For participants with high-risk DLBCL, up to 2 additional cycles of rituximab or biosimilar are given. During the study, participants are monitored for response to treatment using Lugano Response Criteria, with follow-up lasting up to about 31 months for the primary outcome. Secondary outcomes include progression-free survival, overall survival, event-free survival, duration of complete response, adverse events, and quality of life assessments. Safety and health status are regularly checked through exams, lab tests, and questionnaires over several years, with total study participation extending up to 7 years.