Portsmouth

Researchers are studying the effectiveness and safety of a combination inhaler containing fluticasone propionate and albuterol sulfate delivered through a multidose dry powder inhaler with an electronic module (Fp/ABS eMDPI). This Phase 3 trial focuses on people aged 12 years and older who have asthma. The study also looks at the safety and tolerability of this inhaler when used four times daily over four weeks, as well as the pharmacokinetics of the combination and its individual components after a single dose. Participants will be randomly assigned to receive either the Fp/ABS combination inhaler, fluticasone propionate alone, albuterol sulfate alone, or a placebo inhaler. All treatments are given as inhalation powders. The main treatment period lasts four weeks, during which the inhalers are taken four times a day. The total study duration for each participant is about 10 weeks, not counting an optional prescreening visit. Throughout the study, researchers will measure lung function changes, specifically forced expiratory volume in one second (FEV1), from baseline to week 4. Participants will undergo assessments including lung function tests and safety evaluations. The study monitors how the inhaler affects breathing over time and checks for any side effects or tolerability issues during the treatment period.

This research aims to compare the long-term safety of ustekinumab with other biologic therapies in adults diagnosed with Crohn's disease or ulcerative colitis. The study focuses on estimating and comparing the rates of overall cancer, serious infections, and opportunistic infections among new users of these treatments. Participants include adults who have recently started either ustekinumab or other biologic drugs for their condition. Participants are grouped based on whether they are new users of ustekinumab or other biologics such as infliximab, adalimumab, or vedolizumab, as recorded in prescription records. No study treatments are administered as part of this observational study; instead, researchers monitor naturally occurring outcomes. The study leverages medical records from the Department of Defense electronic health database to track treatment exposure and outcomes. Throughout the study, participants' health records will be reviewed for occurrences of malignancies and infections over a period of up to ten years and three months. Researchers will assess the incidence rates of these events to understand the long-term safety profile of ustekinumab compared to other biologics. No direct interventions or treatments are given during the study, and safety monitoring is based on existing health data.

Researchers are evaluating treatments for children and young adults with newly diagnosed acute myeloid leukemia (AML), with or without FLT3 gene mutations. This phase III trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or the FLT3 inhibitor gilteritinib. The study aims to find out which treatment improves event-free survival, overall survival, and minimal residual disease rates, while also monitoring heart function and other effects during and after therapy. Participants are assigned to different treatment arms based on their AML risk group and FLT3 mutation status. Treatments include combinations of intravenous and intrathecal chemotherapy drugs such as cytarabine, daunorubicin, gemtuzumab ozogamicin, dexrazoxane, etoposide, mitoxantrone, asparaginase, and methotrexate. Gilteritinib is given orally to patients with FLT3 mutations alongside chemotherapy. Treatment phases include multiple induction cycles, intensification cycles, and for some, allogeneic stem cell transplantation followed by maintenance therapy with gilteritinib. Throughout the study, participants undergo regular assessments including blood tests, bone marrow biopsies, imaging scans like MRI and CT, cardiac function monitoring, and neuropsychological testing. Researchers track event-free survival up to 3 years, changes in heart function, leukemia response, and neurocognitive effects. Optional cognitive tests are offered at several time points. The study also collects blood samples for pharmacokinetic and biomarker analyses to better understand treatment effects and safety.

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to standard chemotherapy, with or without radiation, can improve survival for patients aged 5 to 60 years with newly diagnosed stage I or II classical Hodgkin lymphoma. This phase III trial compares outcomes in groups based on their early response to initial chemotherapy, aiming to understand if immunotherapy can lead to better progression-free survival and overall survival compared to standard treatment alone. The study also looks at side effects, quality of life, and long-term health impacts across different patient groups. Participants first receive two cycles of standard ABVD chemotherapy every 28 days, followed by imaging to classify their response as rapid or slow early responders and their risk status as favorable or unfavorable. Based on these factors, patients are assigned to one of eight treatment arms that include either continued standard chemotherapy regimens or immunotherapy with brentuximab vedotin and nivolumab, sometimes combined with involved-site radiation therapy. Treatments are given intravenously or orally depending on the drugs, and cycles typically last 28 days. Imaging and blood samples are collected regularly throughout the study. Throughout the trial, participants undergo frequent scans such as FDG-PET, CT, MRI, and PET-CT to monitor their disease status. Blood samples and questionnaires assess treatment effects and quality of life. After completing treatment, patients have scheduled follow-up visits every 3 months for the first year, then every 6 months for two years, and annually up to 12 years to track long-term outcomes, side effects, and survival. The main measurements focus on progression-free survival, overall survival, treatment-related adverse events, and patient-reported experiences.

Researchers are evaluating the effectiveness of active surveillance and chemotherapy treatments in pediatric, adolescent, and adult patients with low risk and standard risk germ cell tumors. This phase III trial focuses on monitoring patients after tumor removal and comparing the outcomes of carboplatin-based versus cisplatin-based chemotherapy regimens. The study aims to maintain high overall survival rates for low risk patients and to compare event-free survival between the two chemotherapy options in standard risk patients. Additional objectives include assessing side effects such as hearing loss and neuropathy, and exploring tumor marker changes and other biological measures related to treatment outcomes. Patients with low risk stage I germ cell tumors undergo surgery followed by observation, with the option to transfer to standard risk treatment if the tumor recurs. Those with standard risk tumors are randomly assigned to one of four chemotherapy regimens combining bleomycin, etoposide, carboplatin, or cisplatin. Treatments are given intravenously on specific schedules every 21 days for up to 3 or 4 cycles, depending on the group. Throughout the trial, patients receive imaging scans, blood tests, tumor biopsies if needed, and pulmonary function tests to monitor treatment response and side effects. Participants are closely followed after treatment completion with regular visits every 2 months for the first year, then less frequently up to 10 years. Researchers collect data through imaging, blood samples, lung tests, and questionnaires to measure survival, disease recurrence, and side effects like hearing loss. The study also includes exploratory analyses of tumor markers and patient-reported outcomes to better understand treatment impacts and improve future care for germ cell tumor patients.

Upper and lower extremity fractures are common in children and teenagers, occurring in about 1 in 5 during childhood. This research compares different types of casts used to treat these fractures, focusing on how cast art or customization affects patient satisfaction and pain perception. The study aims to find out if adding art or color to casts improves the experience for children wearing them. Participants are randomly assigned to one of three groups: a plain white cast, a cast wrapped in a color chosen by the participant, or a cast decorated with custom art including drawings, multiple colors, or glitter. These casts are applied during the treatment period to immobilize the injury and promote healing, with the choice of cast style being the main difference between groups. Throughout the study, satisfaction will be measured using a visual analog scale at 0-2 weeks post injury, 4-6 weeks, and 8-12 weeks if needed. Researchers will also assess pain scores and compare results among the three cast types. Participants will attend orthopedic clinic visits for injury evaluation and have radiographic and clinical data reviewed as part of their care and study assessments.

Researchers are evaluating whether breast conservation surgery combined with endocrine therapy can achieve a similar rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation surgery followed by breast radiation and endocrine therapy in patients with Stage I, hormone sensitive, HER2-negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial builds on the established role of radiation after lumpectomy, aiming to identify if radiation can be safely omitted in certain low-risk patients to reduce treatment burden and side effects. Participants receive either breast radiation plus endocrine therapy or endocrine therapy alone. Radiation therapy involves external beam radiation to the whole breast with or without a boost, partial breast irradiation, or accelerated partial breast irradiation, starting within 12 weeks after the last breast surgery. Endocrine therapy is given for a minimum of 5 years, with the specific drug choice and schedule determined by the treating physician. Endocrine therapy may begin before, during, or after radiation therapy, depending on the treatment group. Throughout the study, participants undergo regular assessments including imaging such as mammograms or MRI within six months before enrollment, and clinical evaluations to monitor tumor recurrence. The main outcome measured is the time to invasive or non-invasive ipsilateral breast tumor recurrence over five years. Safety, adherence to therapy, and recovery from surgery are also monitored. The total participation period includes at least five years to evaluate long-term recurrence rates.

Researchers are evaluating the addition of dinutuximab to standard induction chemotherapy combined with surgery, radiation, stem cell transplantation, and immunotherapy for treating children newly diagnosed with high-risk neuroblastoma. This phase III trial aims to compare event-free survival between patients receiving early chemoimmunotherapy during induction and those receiving standard treatment. The study also explores treatment responses, overall survival, toxicities, tumor biology, quality of life, and long-term effects related to this intensive treatment approach. Participants receive induction therapy starting with cyclophosphamide and topotecan, then are randomized to either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery. Induction involves several chemotherapy cycles with tumor resection after cycles 4 or 5. Patients with good tumor response proceed to consolidation, including two stem cell transplants with high-dose chemotherapy and radiation. Those with poor response receive extended induction chemoimmunotherapy with temozolomide, irinotecan, and dinutuximab. Post-consolidation therapy includes dinutuximab and isotretinoin to maintain treatment effects. Throughout the study, participants undergo blood and urine collection, imaging scans (CT, MRI, I-MIBG, FDG-PET), bone marrow tests, and heart function assessments. Researchers monitor treatment effects, tumor response, side effects, and long-term survival for up to 10 years. Outcome measures focus on event-free survival up to 3 years, with additional assessments of response rates, toxicity, and quality of life. Regular follow-ups occur at multiple intervals after treatment completion to support ongoing evaluation and care.

Researchers are evaluating the effectiveness and safety of rimegepant compared to a placebo for preventing migraines in children and adolescents aged 6 to under 18 years who experience episodic migraine. This Phase 3 study focuses on participants who have had migraines for at least six months with a limited number of headache and migraine days per month. The study aims to understand how well rimegepant works to reduce the number of migraine days over a 12-week period. Participants will receive either rimegepant in doses of 75mg or 50mg (two 25mg orally disintegrating tablets) or a matching placebo. The treatment is administered over a double-blind 12-week phase where neither the participants nor the researchers know which treatment is given. This setup helps ensure unbiased results when comparing the preventive effects of rimegepant against placebo. Throughout the study, participants will be monitored for changes in their migraine frequency, specifically the average number of migraine days per month from the start to the end of the 12 weeks. Evaluations include headache and migraine tracking, as well as assessments of daily activity disruption. Safety and side effects will also be closely observed to understand the medication's impact on young patients.

Researchers are evaluating whether adding inotuzumab ozogamicin to post-induction chemotherapy and immunotherapy improves outcomes for children and young adults with High-Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). This phase III trial also studies patients with Mixed Phenotype Acute Leukemia (MPAL) and B-lymphoblastic lymphoma (B-LLy) treated with standard acute lymphoblastic leukemia therapy. Inotuzumab ozogamicin is a monoclonal antibody linked to chemotherapy that targets cancer cells by binding to the CD22 protein, delivering chemotherapy directly to leukemia cells. The study aims to understand if this addition maintains or improves event-free survival over five years and examines side effects, treatment adherence, immune impact, and social factors affecting outcomes. Participants first undergo induction therapy, receiving multiple chemotherapy drugs and immunotherapy agents such as blinatumomab. After induction, patients with HR B-ALL who test positive for CD22 are randomized into two groups: one receiving standard chemotherapy with blinatumomab (Arm D), and the other receiving chemotherapy with inotuzumab ozogamicin replacing parts of consolidation and delayed intensification therapy (Arm E). Patients with MPAL and B-LLy receive adapted chemotherapy regimens. Treatments include intravenous, oral, and intrathecal administration of various drugs, with some patients receiving additional radiation therapy for testicular or central nervous system involvement. During the study, participants undergo regular assessments including blood and bone marrow tests, and imaging scans for B-LLy patients. The study measures event-free survival up to five years, tracking events such as relapse, second cancers, or treatment failures. Patient-reported outcomes and quality of life measures are collected to evaluate side effects and adherence. After treatment completion, patients are followed closely with visits at 4 weeks, every 3 months for 2 years, then less frequently up to 5 years to monitor long-term outcomes and safety.