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 dAurelle. 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 treatments 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, PETCT 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 the use of donor cytotoxic T lymphocytes CTLs to treat patients who have malignancies associated with BK andor JC virus infections. These CTLs are specially grown from donated blood cells to target viruses that often cause infections in transplant patients. The study aims to assess the effectiveness, feasibility, and safety of these BK-specific CTLs administered to patients with various malignancies, HIVAIDS, or a history of solid organ transplant who have BK and JC infections. Participants will receive allogeneic BK-specific cytotoxic T-lymphocytes through an intravenous infusion lasting about 30 minutes. Those showing partial response, stable disease, or progression may receive up to 19 additional CTL infusions at least two weeks apart if they remain eligible. After completing the CTL treatments, participants will be followed for up to 12 months to monitor health and treatment effects. During the study, participants will undergo regular assessments including response evaluation within 56 days, monitoring for graft-versus-host disease within 28 days after the last infusion, and adverse event tracking up to 100 days. Additional measures include overall survival and kidney function tests monitored up to 12 months after treatment. The study includes laboratory biomarker analyses to support correlative research and involves periodic follow-up visits to track participants health and treatment 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 treatments 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 is common among adults but usually does not cause illness except in people with weakened immune systems. Researchers are evaluating intravenous brincidofovir BCV, an antiviral drug approved for smallpox, to see if it can help treat people with PML. This pilot study focuses on safety, tolerability, and the biological and clinical effects of BCV in adults with PML. Participants will receive BCV intravenously twice a week for a 4-week treatment cycle. If the drug shows benefit, they may receive up to three cycles over 12 weeks. Before and after each treatment cycle, participants will have brain imaging scans with contrast dye, lumbar punctures to collect spinal fluid, and other tests. After treatment ends, participants will be monitored for up to 12 months with six follow-up visits including repeated scans, spinal taps, and assessments. During the study, participants will undergo physical exams, blood tests, brain imaging, and spinal fluid collection to track their condition and response to treatment. Researchers will measure treatment-related adverse events, changes in JC virus levels in spinal fluid, brain lesion burden, disability scores, and survival over 12 months. This comprehensive monitoring aims to evaluate the safety and potential antiviral effects of BCV in managing PML.

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 diseases 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 JC virus, which usually remains inactive in most people but can become active if the immune system is weakened due to disease or medication. The study aims to understand the natural history and effects of PML on the immune system by following patients with PML and individuals at risk, alongside healthy volunteers. Participants include those with suspected or confirmed PML, individuals with impaired immune function who may be at risk for PML, and healthy volunteers. The study involves multiple visits including an initial visit, monthly visits for six months, a 12-month visit, and possible additional visits. During these visits, participants undergo physical exams, neurological tests, brain imaging, and provide blood, urine, and spinal fluid samples. Optional procedures may include bone marrow samples and skin biopsies. No treatment is provided as part of the study. Participants will be monitored over time with detailed clinical and imaging assessments to collect data on the diseases course and immune response. The research includes evaluating viral behavior, immune markers, and genetic factors. The main measurement focuses on characterizing patients at one year after enrollment, with follow-up assessments to track progression. This long-term observation helps to develop tools for earlier diagnosis and better management of PML.

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 mgkg per day, split into two doses, while the other group takes oral Dexamethasone tablets on weekends at 0.05 0.025 mgkg 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 childrens overall health and treatment effects are closely observed.

Researchers are studying the risk of progressive multifocal leukoencephalopathy PML, a rare brain infection caused by the John Cunningham virus JCV, in people with multiple sclerosis treated with ozanimod. The study aims to describe characteristics of patients who develop PML and estimate how often it occurs among those exposed to ozanimod. Factors such as age, duration of ozanimod use, previous immunosuppressant treatments, lymphopenia, and JCV antibody status will be evaluated for their association with PML. This observational study focuses on participants who have received at least one dose of ozanimod and developed PML. The study does not involve administering new treatments but collects and reviews reported cases from various sources including spontaneous reports, post-marketing observational studies, and patient support programs. PML cases must be confirmed as definite or probable and related to ozanimod by an adjudication committee. Participants are identified through adverse event reports from June 4, 2026, through July 31, 2041. Researchers will analyze patient data to determine the proportion of PML cases based on participant characteristics and potential risk factors over a follow-up period of up to 15 years. The incidence rate of PML among ozanimod-exposed patients will also be assessed. There is no direct participant involvement beyond data collection from reported cases.