Progressive Multifocal Leukoencephalopathy (PML)

Researchers are evaluating the use of two additional cycles of Lutathera4 (a type of peptide receptor radionuclide therapy) compared to active surveillance in patients with intestinal well-differentiated neuroendocrine tumors (NETs) who have shown new disease progression after previous treatments. This study responds to varying clinical practices in France regarding retreatment cycles and aims to assess if additional Lutathera4 cycles can provide benefit in this setting. The trial is a randomized phase II study sponsored by the Institut du Cancer de Montpellier - Val d'Aurelle. Participants are randomly assigned to receive either two more infusions of Lutathera4 spaced eight weeks apart according to approved guidelines or to undergo active monitoring without additional treatment. Active surveillance involves clinical, biological, and radiological follow-up every two months. This design allows comparison between retreatment and observation in patients who have already received four initial cycles and two retreatment cycles previously. During the study, patients will be closely monitored through clinical exams, imaging tests such as CT or MRI scans, and laboratory tests at regular intervals. Researchers will assess the treatment's effectiveness by measuring disease progression every eight weeks over six months, as well as safety, progression-free survival, overall survival, and quality of life during treatment and for up to five years. Monitoring will ensure participant safety and collect data on long-term outcomes over several years, with scheduled assessments continuing for four years after treatment completion.

Researchers are studying multiple sclerosis (MS), progressive multifocal leukoencephalopathy (PML), and other neuroinflammatory diseases that affect the central nervous system (CNS), including the brain, spinal cord, and optic nerves. These diseases can cause muscle weakness and problems with vision, speech, and coordination. The study aims to evaluate whether an experimental radioactive tracer called a minibody can help PET scans detect certain immune cells called CD8 plus T cells in the CNS of adults with these conditions. Participants will receive an intravenous injection of the minibody tracer during study visits. The study includes separate groups for MS, PML, and other neuroinflammatory diseases with a breakdown of up to four visits for MS and other diseases, and up to seven visits for PML. Visits involve MRI scans of the brain and spinal cord with contrast, PET/CT scans on consecutive days, and optional additional PET scans. The PML group may have a repeat minibody injection and PET scan within six months to assess changes over time. During the study, participants will undergo physical and neurological exams, blood tests, heart function tests before and after minibody injection, and an MRI brain scan. Some may have a spinal tap to collect spinal fluid. PET scans will take about one hour, with participants lying on a table moving through a scanning machine. Researchers will measure how well the minibody identifies immune cells in different CNS tissues and monitor safety and tolerability. The study will last about 4 to 6 weeks, with some participants possibly followed for up to six months.

Researchers are evaluating how well donor cytotoxic T lymphocytes (CTLs) work in treating patients with malignancies who have BK and/or JC virus infections. This phase II study aims to assess the effectiveness, safety, and feasibility of giving BK-specific CTL lines that are closely matched to the patient's human leukocyte antigen (HLA) to fight these viral infections. The study also examines how long the infused CTLs persist in the body of patients with malignancies, HIV/AIDS, or a history of solid organ transplant who have BK and JC infections. Patients receive intravenous infusions of allogeneic BK-specific cytotoxic T lymphocytes over 30 minutes. After the first infusion, those who show partial response, stable disease, or progressive disease may receive up to 19 additional infusions, each given at least two weeks apart, if they meet the criteria for further treatment. The treatment period is followed by regular monitoring and assessments. Participants undergo evaluations including response to treatment, monitoring for acute graft-versus-host disease within 28 days after the last CTL dose, and tracking of adverse events up to 100 days. They are followed up periodically for 12 months after completing treatment to assess overall survival and kidney function. The study involves laboratory biomarker analysis as part of correlative studies to better understand treatment effects and patient outcomes.

Researchers are evaluating FT536, a new type of natural killer (NK) cell immunotherapy, in adult patients with recurrent WHO Grade 4 astrocytoma, a severe brain tumor. This Phase I trial includes patients eligible for repeat brain surgery at the time of their first or second tumor recurrence, regardless of their IDH mutation status. The study aims to assess the safety and tolerability of this treatment over one year. FT536 will be given as a single injection directly into the tumor during surgery. The treatment involves three dose levels, ranging from 10 million to 60 million cells. Initially, the suspicious tumor area will be biopsied to confirm recurrence, followed by injection of FT536. About one to two weeks later, patients will have a second surgery to remove as much tumor as safely possible. Postoperative MRI scans will assess surgical outcomes and possible side effects. Participants will undergo blood tests to evaluate their immune cells and cytokines throughout the study. Cerebrospinal fluid samples will also be collected at several points to analyze immune responses. The research team will compare tumor tissue before and after FT536 injection to study the treatment's movement, replication, and impact on tumor cells and the immune environment. The entire participation period includes initial biopsy, FT536 injection, tumor removal surgery, and follow-up assessments for safety and immune monitoring.

Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal brain infection caused by the JC virus, which commonly infects adults but usually does not cause illness unless the immune system is weakened. Researchers are studying intravenous Brincidofovir (BCV), an antiviral drug approved for smallpox, to see if it can help people with PML. This pilot study focuses on safety, tolerability, and preliminary effects of BCV in adults diagnosed with PML confirmed by positive JC virus DNA in spinal fluid. Participants will receive BCV through a vein twice a week for 4 weeks per treatment cycle, with up to three cycles totaling 12 weeks if the drug shows benefit. After each cycle, brain imaging scans, spinal taps, and other tests will be repeated to monitor progress. Following treatment, participants will have monthly evaluations for three months to decide whether to continue treatment or monitoring. They will be followed for up to one year after treatment ends with repeated scans, spinal taps, and tests at six follow-up visits to assess changes in disease and safety. During the study, people will undergo physical exams, blood tests, brain MRI with contrast dye, and lumbar punctures to collect spinal fluid. Researchers will monitor safety by recording treatment-related side effects and measure viral loads in spinal fluid to evaluate antiviral effects. They will also assess changes in clinical symptoms, disability scores, brain lesion size, and survival up to 12 months after treatment. Participation includes regular visits over about 15 months from screening through follow-up to track treatment impact and safety.

This research investigates Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL), a rare genetic disorder causing progressive problems with movement, coordination, and some cognitive functions. The study aims to understand the range and progression of neuromotor and neurocognitive impairments in individuals with LBSL by reviewing past medical records and performing ongoing virtual assessments. The goal is to better characterize the disease's natural history and link symptoms to genetic factors, helping guide future care and treatment development. Participants will undergo retrospective review of medical charts and imaging studies, along with prospective longitudinal virtual evaluations. These virtual assessments include standardized surveys to measure behavior, social communication, executive function, adaptive skills, and quality of life. Wearable sensor technology and clinical tests like the Timed Up and Go and Long Walk Test will assess ataxia and balance. The study does not involve drug interventions but focuses on detailed observation and data collection. Throughout the study, participants will be involved in virtual assessments and their past medical data will be reviewed to track changes over time. Researchers will measure motor and cognitive function, quality of life, and movement abilities using specialized surveys and wearable devices. The study started in April 2018 and will continue monitoring participants through May 2029, aiming to gather extensive data to inform future supportive therapies and treatment priorities for LBSL patients.

Progressive multifocal leukoencephalopathy (PML) is a serious brain infection caused by the reactivation of the JC virus, which usually remains controlled by a healthy immune system. This research aims to better understand how PML develops and progresses, especially in people with weakened immune systems from various conditions or treatments. The study also includes patients at risk for PML and healthy volunteers to explore potential biomarkers for early diagnosis and risk assessment. Participants include those with suspected or confirmed PML, individuals with impaired immune function at risk for PML, and healthy volunteers. Participants will undergo detailed clinical, imaging, and laboratory assessments over time. Visits include an initial evaluation, monthly visits for six months, a 12-month visit, and possible follow-up visits. Samples such as blood, urine, cerebrospinal fluid, and optional bone marrow and skin biopsies will be collected. No treatments are provided as part of the study. During the study, participants will undergo neurological tests, brain imaging, and sample collection to monitor disease features and immune responses. Researchers will analyze clinical, radiological, immunological, genetic, and viral data to characterize disease presentation and progression. The study aims to develop a disease-specific assessment scale for PML and create a repository of biological samples for future research. Participation may last more than a year with scheduled follow-ups.

Researchers are conducting a real-world observational cohort study to understand chronic viral infections in the central nervous system (CNS), such as Progressive Multifocal Leukoencephalopathy (PML). The study aims to evaluate whether immune checkpoint inhibitors, a type of drug, improve long-term outcomes for patients with these infections. Both patients with existing follow-up data and newly diagnosed patients will be enrolled to gather comprehensive information. Participants will be grouped into two cohorts: an ambidirectional cohort for those with prior follow-up data and a prospective cohort for newly diagnosed cases. The study involves monitoring patients over time without assigning treatments, focusing on observing their health and response to any use of immune checkpoint inhibitors. Participants will be followed for at least one year after disease onset, with regular assessments including neurological function tests using the Modified Rankin Scale (mRS), neuroimaging scans, and cerebrospinal fluid tests to detect viral DNA. Evaluations occur at one month, then every three months, to measure symptoms and neurological changes. This comprehensive monitoring helps researchers understand disease progress and treatment impact over time.

This clinical trial studies children aged 4 to 12 years with rapidly progressing vitiligo, an autoimmune skin condition causing pigment loss. The research compares the safety and effectiveness of two treatments: oral Tacrolimus capsules and Dexamethasone micro-pulse therapy. The goal is to find which treatment better controls disease progression and improves quality of life for affected children. The study is multicenter and randomized, enrolling 90 participants divided equally into two groups. One group receives oral Tacrolimus capsules daily at a dose of 0.1 ± 0.05 mg/kg per day, split into two doses, while the other group takes oral Dexamethasone tablets on weekends at 0.05 ± 0.025 mg/kg per dose. Both treatments continue for 24 weeks with follow-up visits at 4, 8, 12, 16, 20, and 24 weeks. Blood drug concentrations and safety assessments, including blood tests and adrenal function monitoring, are part of the treatment protocols. Participants attend regular check-ups over 24 weeks to monitor skin repigmentation using the Vitiligo Area Scoring Index (VASI) and Investigator Global Assessment (IGA) scores. Safety is tracked by blood tests, metabolic panels, and adverse event reporting. The main outcome is the proportion of children achieving at least 50% improvement in vitiligo severity at 24 weeks. This trial lasts six months, during which children's overall health and treatment effects are closely observed.

Researchers are evaluating genetically modified cytotoxic T-lymphocytes (CTLs) designed to target infections caused by adenovirus, BK virus, cytomegalovirus, JC virus, or COVID-19 in immunocompromised cancer patients. This phase I trial aims to test the feasibility and safety of these virus-specific CTLs in controlling viral infections, which are a serious cause of illness and death after hematopoietic stem cell transplantation. The study also seeks preliminary data on treatment efficacy, cell persistence, and survival outcomes. Participants receive virus-specific CTLs through an intravenous infusion over 30 minutes. Depending on their response—partial, stable, or progressive disease—they may receive up to eight additional infusions spaced at least two weeks apart. After completing treatment, patients are monitored with yearly follow-ups for 15 years to assess long-term effects and outcomes. During the study, patients undergo evaluations including viral testing, clinical assessments, and monitoring of overall survival as the primary outcome. Researchers track the persistence of the infused cells and gather data on relapse-free and overall survival. The long-term follow-up period ensures ongoing observation of safety and durability of the treatment effects, with total participation potentially spanning many years.